Amyloidosis
Conditions
Keywords
miridesap, GSK2315698, 89Zirconium labelled, Positron Emission Tomography, Transthyretin cardiomyopathy, GSK2398852, dezamizumab
Brief summary
The principal aim of this study is to investigate the cardiac uptake of 89Zr-GSK2398852 in subjects with transthyretin cardiomyopathy amyloidosis (ATTR-CM), and its biodistribution to other organs. Low doses of GSK2398852 will be co-administered at levels not high enough for therapeutic benefit. This study will be conducted in two parts: Part A and Part B. Subjects in Part A will participate in up to two dosing sessions and subjects in Part B will participate in one dosing session. Subjects will undergo up to 3 PET scans at varying intervals after 89Zr-GSK2398852 administration. The total duration of study will be approximately 3 to 4 months for subjects in Part A and approximately 2 months for subjects in Part B. Part B of the study will be triggered based on data obtained in Part A and other emerging data.
Interventions
DRUGGSK2398852 (unlabeled anti-SAP mAb)
Subjects will be administered up to 490 mg of GSK2398852, IV. Dose level will be adjusted based on emerging imaging data.
GSK2315698 will be administered as 20 milligrams per hour (20 mg/hour) IV infusion (in the vein) for up to 72 hours followed by 60 milligrams (mg) three times daily as SC injection for 8 days. Dose level and frequency will be adjusted according to renal function.
DRUG89Zr-GSK2398852 (89Zr-labeled anti-SAP mAb)
89Zr-GSK2398852 will be available as solution containing 10 mg 89Zr-GSK2398852 for Infusion. Subjects will be administered 37 (Megabecquerel) MBq radioactive dose of 89Zr-GSK2398852 by the IV route at each dosing session.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Part A of the study will include 3 subjects with ATTR-CM who will participate in two dosing sessions and Part B of the study will include 3 subjects with ATTR-CM who will participate in one dosing session. A single dosing session will constitute treatment with carboxy pyrrolidine hexanoyl pyrrolidine carboxylate (CPHPC), total mass dose (TMD) administration of anti-serum amyloid P (SAP) monoclonal antibody (mAb) consisting of in vivo mixing of a single infusion of unlabeled anti-SAP mAb and a separate infusion of 89Zr-GSK2398852 via a different peripheral venous line, and up to 3 serial PET scanning procedures after administration of 89Zr-GSK2398852.
Eligibility
Sex/Gender
ALL
Age
65 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subject must be 65 to 80 years of age inclusive, at the time of signing the informed consent. * Subjects with a diagnosis of ATTR-CM: a) Wild-type ATTR status must be confirmed by genotyping and have one of the following: i) Definite histochemical identification of amyloid by Congo red staining and green birefringence in crossed polarized light in cardiac or other tissue biopsy and identification of Transthyretin amyloidosis (TTR) as the amyloid fibril protein either by immunohistochemistry or proteomic analysis OR ii) Scintigraphy Technetium-99m-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) with confirmed myocardial uptake. b) Hereditary ATTR amyloidosis (example, TTR Val30Met) should have a known amyloidogenic TTR mutation demonstrated by genotyping and is recognized to be primarily associated with cardiomyopathy and one of the following: i) Definite histochemical identification of amyloid by Congo red staining and green birefringence in crossed polarized light in cardiac or other tissue biopsy and identification of TTR as the amyloid fibril protein either by immunohistochemistry or proteomic analysis. ii) Scintigraphy: 99mTc-DPD with confirmed myocardial uptake. * Both male and female subjects are eligible to participate. a) Male subjects: A male subject must agree to use contraception during the treatment period and for at least 3 months after the last scan and refrain from donating sperm during this period. b) Female subjects: A female subject is eligible to participate if she is not of childbearing potential. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol. * New York Heart Association (NYHA) up to class 3; subjects should be clinically stable for at least 3 months preceding to Screening.
Exclusion criteria
* Cardiomyopathy primarily caused by non-amyloid diseases (example, ischemic heart disease; valvular heart disease). * Interval from the Q wave on the ECG to point T using Fredericia's formula (QTcF) \>500 milliseconds (msec). * Sustained (at a rate of \>=120 beats per minute for \>=30 seconds), or symptomatic monomorphic ventricular tachycardia (VT), or rapid polymorphic VT, at Screening/Baseline cardiac monitoring. * Systolic blood pressure \<=100 millimeters of mercury (mm/Hg) based on triplicate readings at Screening. * Unstable heart failure defined as emergency hospitalization for worsening, or decompensated heart failure, or syncopal episode within 1 month of screening. * Implantable cardiac defibrillator (ICD) or permanent pacemaker (PPM) at Screening. * Estimated Glomerular filtration rate (eGFR) at Screening \<50 milliliters per minute (mL/min) calculated using modification of diet in renal disease (MDRD). * Any active and persistent dermatological condition, which in the opinion of the Investigator and Medical Monitor would preclude safe participation. * History of allogeneic stem cell transplantation, prior solid organ transplant, or anticipated to undergo solid organ transplantation, or left ventricular assist device (LVAD) implantation. * Malignancy within last 5 years, except for basal or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix that has been successfully treated. * Acute coronary syndrome, or any form of coronary revascularization procedure (including coronary artery bypass grafting \[CABG\]), within 6 months of screening. * Symptomatic, clinically significant autonomic neuropathy which the Principal Investigator (PI) feels will preclude administration of study treatment. * Uncontrolled hypertension during Screening. * ALT \>3 times upper limit of normal (ULN) OR bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Peripheral edema at Screening that in the opinion of the PI or designee might prevent adequate absorption of subcutaneously administered CPHPC. * Presence of any co-morbid (example, steroid refractory rheumatoid arthritis), or an uncontrolled medical condition (example, diabetes mellitus), which in the opinion of the investigator would increase the potential risk to the subject. Investigator should liaise with the Medical Monitor where there is uncertainty as to the eligibility of a subject. * Positive test for hepatitis B, hepatitis C and/or human immunodeficiency virus (HIV) during Screening, or within 3 months prior to first dose of study treatment. * Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A \[IgA\] dermatosis, toxic epidermal necrolysis and exfoliative dermatitis). * Inability to comprehend and/or understand the study patient information sheet, and/or unwillingness or inability to follow the procedures outlined in the protocol. * Has any of the following: a) Fulfillment of diagnostic criteria for Amyloid Light-chain (AL) amyloidosis. b) Fulfillment of diagnostic criteria for amyloid A (AA) or non-TTR hereditary amyloidosis. * ATTR Disease Load: c) Histologically proven or clinically suspected gastrointestinal TTR amyloidosis; d) Diffuse skeletal muscle uptake of 99m(Tc)-DPD on Single-photon emission computed tomography (SPECT) imaging (where available); e) Peripheral neuropathy causing more than mild morbidity (example, walking disability; neuropathic pain affecting activities of daily living); f) Proven or clinically suspected intracranial TTR involvement including ophthalmological disease. * Non-amyloidosis related chronic liver disease (with the exception of Gilbert's syndrome or clinically asymptomatic gallstones). * Participation in a separate clinical trial involving CPHPC within 3 months of Screening. * Any prohibited concomitant medication within referenced timeframe. * Treatment with another investigational drug, biological agent, or device within 6 months of screening, or 5 half-lives of the study agent, whichever is longer. * Orthopnea of sufficient severity to preclude supine scanning as determined at Screening. * Inability to fit inside scanner due to body size (girth). * History of claustrophobia. * Contraindication to magnetic resonance imaging (MRI) contrast agents. * Contraindication for MRI scanning (as assessed by local MRI safety questionnaire), which includes but is not limited to: a) Intracranial aneurysm clips (except Sugita) or other metallic objects; b) Intra-orbital metal fragments that have not been removed; c) Pacemakers or other implanted cardiac rhythm management/monitoring devices and non-magnetic resonance (MR) conditional heart valves; d) Inner ear implants. * Donation of blood or blood products in excess of 500 milliliters (mL) within 84 days of Screening. * Poor or unsuitable venous access.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session 1: Days 4, 5, 6 and 8 | SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as blood pool left atrium, blood pool left ventricle, blood pool right ventricle, left ventricle wall - high uptake, left ventricle wall - low uptake, mid septum - high uptake and mid septum - low uptake. Peak SUV values derived from PET images has been presented. All treated population consisted of all participants who received at least one Anti-SAP treatment including 89Zr-GSK2398852. |
| Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session 2: Days 3, 4 and 5 | SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as blood pool left atrium, blood pool left ventricle, blood pool right ventricle, left ventricle wall - high uptake, left ventricle wall - low uptake, mid septum - high uptake and mid septum - low uptake. Peak SUV values derived from PET images has been presented. |
| Part B: Peak SUV in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Days 3, 4 and 6 | SUV in focal anatomical regions of the heart was planned to be measured. |
| Part B: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Days 3, 4 and 6 | SUV in focal anatomical regions of the heart was planned to be measured. |
| Part A- Session 1: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb | Session 1: Days 4, 5, 6 and 8 | SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. |
| Part A- Session 2: Mean SUV of Whole Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session 2: Days 3, 4 and 5 | SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. |
| Part B: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb | Days 3, 4 and 6 | SUV of whole heart was planned to be measured. |
| Part B: Mean SUV of Whole Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Days 3, 4 and 6 | SUV of whole heart was planned to be measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Testes | Session 1: Days 4, 5 and 8 | SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for testes. Mean SUV derived from PET images has been presented. |
| Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session 2: Days 3, 4, and 5 | SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as adrenal gland, aorta, bone marrow, kidney, liver, spleen, abdominal region, brain, lung, parotid gland, thigh, and thyroid gland- goitre. Mean SUV derived from PET images has been presented. |
| Part B: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Days 3, 4 and 6 | SUV of total radioactivity uptake for different organs/tissues was planned to be measured. |
| Part B: Mean SUV of Total Radioactivity Uptake After an Anti-SAP mAb Dose Between 200 mg and <=500 mg | Days 3, 4 and 6 | SUV of total radioactivity uptake for different organs/tissues was planned to be measured. |
| Part A: Maximum Concentration in Plasma (Cmax) of Total mAb | Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7 | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852). PK Population consisted of all participants from the All Treated Population for whom a PK sample was obtained and analyzed. |
| Part B: Cmax of Total mAb | Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8 | Blood samples were planned to be collected at indicated time points for PK analysis of total mAb. |
| Part A: Time Associated With Cmax (Tmax) of Total mAb | Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7 | Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852). |
| Part B: Tmax of Total mAb | Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8 | Blood samples were planned to be collected at indicated time points for PK analysis of total mAb. |
| Part A: Clearance of Total mAb | Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7 | Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852). |
| Part B: Clearance of Total mAb | Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8 | Blood samples were planned to be collected at indicated time points for PK analysis of total mAb. |
| Part A: Terminal Half-life (T1/2) of Total mAb | Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7 | Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852). |
| Part B: T1/2 of Total mAb | Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8 | Blood samples were planned to be collected at indicated time points for PK analysis of total mAb. |
| Part A:Area Under the Concentration Time Curve Till Last Observation (AUC[0 to t]) of Total mAb | Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7 | Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852). |
| Part B: AUC(0 to t) of Total mAb | Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8 | Blood samples were planned to be collected at indicated time points for PK analysis of total mAb. |
| Part A: Area Under the Concentration Time Curve Till Time Infinity (AUC[0 to Infinity]) of Total mAb | Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7 | Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852). |
| Part B: AUC(0 to Infinity) of Total mAb | Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8 | Blood samples were planned to be collected at indicated time points for PK analysis of total mAb. |
| Part A: Cmax of 89Zr-GSK2398852 PKs of Radioactivity (Radio-PK) | Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6 | Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter. |
| Part B: Cmax of 89Zr-GSK2398852 Radio-PK | Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6 | Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter. |
| Part A: Tmax of 89Zr- GSK2398852 Radio-PK | Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6 | Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter. |
| Part B: Tmax of 89Zr-GSK2398852 Radio-PK | Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6 | Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter. |
| Part A: T1/2 of 89Zr- GSK2398852 Radio-PK | Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6 | Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter. |
| Part B: T1/2 of 89Zr- GSK2398852 Radio-PK | Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6 | Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter. |
| Part A: AUC(0 to t) of 89Zr- GSK2398852 Radio-PK | Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6 | Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter. |
| Part B: AUC(0 to t) of 89Zr- GSK2398852 Radio-PK | Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6 | Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter. |
| Part A: AUC(0 to Infinity) of 89Zr- GSK2398852 Radio-PK | Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6 | Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter. |
| Part B: AUC(0 to Infinity) of 89Zr- GSK2398852 Radio-PK | Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6 | Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter. |
| Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Day 26 of the last session | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events which may require medical or surgical intervention. Safety Population consisted of all participants who received at least one dose of GSK2315698, GSK2398852 or 89Zr-GSK2398852. |
| Part B: Number of Participants With AEs and SAEs | Up to Day 26 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events which may require medical or surgical intervention. |
| Part A: Number of Participants With Skin Rashes | Up to Day 26 of the last session | Rash was graded as Grade 1 to Grade 4 based on symptoms and body surface area (BSA) affected; Grade 1: \<10 percent (%) BSA and asymptomatic; Grade 2: 10-30% BSA and/or mild symptoms (pain, itch and burning); Grade 3: \>30% BSA and/or moderate/severe symptoms (pain, itch and burning); and Grade 4: any rash with mucosal or systemic involvement (such as evidence of renal involvement). |
| Part B: Number of Participants With Skin Rashes | Up to Day 26 | Rash was planned to be graded as Grade 1 to Grade 4 based on symptoms and BSA affected; Grade 1: \<10% BSA and asymptomatic; Grade 2: 10-30% BSA and/or mild symptoms (pain, itch and burning); Grade 3: \>30% BSA and/or moderate/severe symptoms (pain, itch and burning); and Grade 4: any rash with mucosal or systemic involvement (such as evidence of renal involvement). |
| Part A: Number of Participants With Cardiac Adverse Events | Up to Day 26 of the last session | The number of participants with any cardiovascular AEs i.e. any AE coded to the cardiovascular system organ class are presented. |
| Part B: Number of Participants With Cardiac Adverse Events | Up to Day 26 | The number of participants with any cardiovascular AEs i.e. any AE coded to the cardiovascular system organ class were planned to be reported. |
| Part A: Number of Participants With Infusion Related Reactions | Up to Day 26 of the last session | Number of participants with any infusion related reactions are presented. |
| Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Session 1: Baseline (Day 1 Pre-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 26; Session 2: Day 1- Pre-dose, Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 26 | Blood samples were collected to analyze the troponin T and NT-ProBNP at indicated time points. Baseline was considered as the latest assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value. |
| Part B: Change From Baseline in Cardiac Troponin T and NT-ProBNP | Baseline and up to Day 26 | Blood samples were planned to be collected to analyze the troponin T and NT-ProBNP at indicated time points. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value. |
| Part A: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Up to Day 26 of the last session | 12-lead ECGs were measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. |
| Part B: Number of Participants With Abnormal 12-lead ECG Findings | Up to Day 26 | 12-lead ECGs were planned to be measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant. |
| Part A: Number of Participants With Abnormal Inpatient Cardiac Telemetry | Up to Day 26 of the last session | Continuous inpatient cardiac monitoring was performed via remote cardiac telemetry device. Abnormal findings were categorized as CS and NCS. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. |
| Part B: Number of Participants With Abnormal Inpatient Cardiac Telemetry | Up to Day 26 | Continuous inpatient cardiac monitoring was planned to be performed via remote cardiac telemetry device. |
| Part A: Number of Participants With Abnormal Outpatient Cardiac Telemetry | Up to Day 26 of the last session | Continuous outpatient cardiac monitoring was performed via remote cardiac bodyguardian telemetry device. Abnormal findings were categorized as CS and NCS. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. |
| Part B: Number of Participants With Abnormal Outpatient Cardiac Telemetry | Up to Day 26 | Continuous outpatient cardiac monitoring was planned to be performed via remote cardiac bodyguardian telemetry device. |
| Part A: Number of Participants With Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Up to Day 26 of the last session | SBP and DBP were measured in a semi-supine position after 5 minutes of rest for the participant. Potential Clinical Importance (PCI) ranges for the SBP and DBP were as follows: SBP- \<90 and \>180 millimeters of mercury (mmHg), and DBP- \<30 and \>110 mmHg. |
| Part B: Number of Participants With Abnormal SBP and DBP | Up to Day 26 | SBP and DBP were planned to be measured in a semi-supine position after 5 minutes of rest for the participant. |
| Part A: Number of Participants With Abnormal Temperature | Up to Day 26 of the last session | Temperature was measured in a semi-supine position after 5 minutes of rest for the participant. Normal range for temperature was as follows: temperature- \>37.5 degree celsius. |
| Part B: Number of Participants With Abnormal Temperature | Up to Day 26 | Temperature was planned to be measured in a semi-supine position after 5 minutes of rest for the participant. |
| Part A: Number of Participants With Abnormal Respiratory Rate | Up to Day 26 of the last session | Respiratory rate was measured in a semi-supine position after 5 minutes of rest for the participant. Normal range for the respiratory rate was as follows: respiratory rate- \<12 and \>25 breaths per minute. |
| Part B: Number of Participants With Abnormal Respiratory Rate | Up to Day 26 | Respiratory rate was planned to be measured in a semi-supine position after 5 minutes of rest for the participant. |
| Part A: Number of Participants With Abnormal Pulse Rate | Up to Day 26 of the last session | Pulse rate were measured in a semi-supine position after 5 minutes of rest for the participant. PCI range for the pulse rate was as follows: pulse rate- \<35 and \>140 beats per minute (bpm). |
| Part B: Number of Participants With Abnormal Pulse Rate | Up to Day 26 | Pulse rate was planned to be measured in a semi-supine position after 5 minutes of rest for the participant. |
| Part A: Number of Participants With New Abnormal Physical Examination Findings | Session 1: At screening (within 35 days of Anti-SAP treatment of session 1), Day 1 Pre-dose, Day 3, Day 5, Day 8 and Day 11; Session 2: Day 1 Pre-dose, Day 3, Day 5, Day 8 and Day 11 | A full and brief physical examination was performed, including assessments of the skin, lungs, cardiovascular system and abdomen (liver and spleen). |
| Part B: Number of Participants With New Abnormal Physical Examination Findings | At screening (within 35 days of Anti-SAP treatment), Days 1, 3, 5, 8 and 11 | A full and brief physical examination was planned to be performed, including assessments of the skin, lungs, cardiovascular system and abdomen (liver and spleen). |
| Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1-Pre-dose, Days 3, 5, 7, 10 and 26 | Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value. |
| Part B: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26 | Blood samples were planned to be collected to analyze the hematology parameters. |
| Part A: Change From Baseline in Hematology Parameter: Hematocrit | Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1-Pre-dose, Days 3, 5, 7, 10 and 26 | Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value. |
| Part B: Change From Baseline in Hematology Parameter: Hematocrit | Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26 | Blood samples were planned to be collected to analyze the hematology parameter. |
| Part A: Change From Baseline in Hematology Parameter: Hemoglobin | Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26 | Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value. |
| Part B: Change From Baseline in Hematology Parameter: Hemoglobin | Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26 | Blood samples were planned to be collected to analyze the hematology parameter. |
| Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26 | Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value. |
| Part B: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26 | Blood samples were planned to be collected to analyze the hematology parameter. |
| Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26 | Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Volume. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value. |
| Part B: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26 | Blood samples were planned to be collected to analyze the hematology parameter. |
| Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26 | Blood samples were collected to analyze the hematology parameters: Erythrocytes and Reticulocytes. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value. |
| Part B: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26 | Blood samples were planned to be collected to analyze the hematology parameters. |
| Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26 | Blood samples were collected to analyze the chemistry parameters: Glucose, Calcium, Potassium, Sodium and Urea. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value. |
| Part B: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26 | Blood samples were planned to be collected to analyze the chemistry parameters. |
| Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26 | Blood samples were collected to analyze the chemistry parameters: Albumin and Protein. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value. |
| Part B: Change From Baseline in Chemistry Parameters: Albumin, Protein | Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26 | Blood samples were planned to be collected to analyze the chemistry parameters. |
| Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26 | Blood samples were collected to analyze the chemistry parameters: ALP, ALT and AST. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value. |
| Part B: Change From Baseline in Chemistry Parameters: ALP, ALT, AST | Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26 | Blood samples were planned to be collected to analyze the chemistry parameters. |
| Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26 | Blood samples were collected to analyze the chemistry parameters: Direct Bilirubin, Bilirubin, Creatinine. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value. |
| Part B: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26 | Blood samples were planned to be collected to analyze the chemistry parameters. |
| Part B: Number of Participants With Infusion Related Reactions | Up to Day 26 | Number of participants with any infusion related reactions were planned to be reported. |
| Part A: Number of Participants With Abnormal Urinalysis Parameters: Specific Gravity, Potential of Hydrogen | Up to Day 26 of the last session | Urine samples were collected to analyze urinalysis parameters including specific gravity and potential of hydrogen. |
| Part B: Number of Participants With Abnormal Urinalysis Parameters: Glucose, Protein, Blood, Ketones | Up to Day 26 | Urine samples were planned to be collected to analyze the urinalysis parameters. |
| Part B: Number of Participants With Abnormal Urinalysis Parameters: Specific Gravity, Potential of Hydrogen | Up to Day 26 | Urine samples were planned to be collected to analyze the urinalysis parameters. |
| Part A: Number of Participants With Abnormal Urinalysis Parameters: Glucose, Protein, Blood, Ketones | Up to Day 26 of the last session | Urine samples were collected to analyze urinalysis parameters including glucose, protein, blood and ketones. |
| Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session 1: Days 4, 5, 6 and 8 | SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as abdominal skin and skin of the back. Mean SUV derived from PET images has been presented. |
| Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyriod Gland-goitre Hotspot | Session 1: Days 4 and 6 | SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for thyroid gland-goitre hotspot. Mean SUV derived from PET images has been presented. |
| Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session 2: Days 3, 4 and 5 | SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as thyroid gland-goitre hotspot, abdominal skin and skin of the back. Mean SUV derived from PET images has been presented. |
| Part B: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Days 3, 4 and 6 | SUV of focal radioactivity uptake for different organs/tissues was planned to be measured. |
| Part B: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Days 3, 4 and 6 | SUV of focal radioactivity uptake for different organs/tissues was planned to be measured. |
| Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session 1: Days 4, 5, 6 and 8 | SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as adrenal gland, aorta, bone marrow, kidney, liver, spleen, abdominal region, brain, lung, parotid gland, and thigh. Mean SUV derived from PET images has been presented. |
| Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyroid Gland-goitre | Session 1: Days 4 and 6 | SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for thyroid gland-goitre. Mean SUV derived from PET images has been presented. |
Countries
Sweden
Participant flow
Recruitment details
This was a two part study. Part A contains two dosing sessions and Part B contain single dosing session. This study was conducted at a single center in Sweden from 06-April-18 to 20-July-2018.
Pre-assignment details
Two participants were enrolled in Part A. The study was terminated by sponsor due to a change in the benefit:risk profile of GSK2315698+GSK2398852 (anti-serum amyloid P component \[SAP\] treatment) during Part A; hence, no participants were enrolled in Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Anti-SAP Participants with either wild type or ATTR-CM were included. Participants underwent two dosing sessions. In each dosing session, participants were administered (dependent on renal function) 20 mg per hour or 10 mg/hour GSK2315698 for 48 hours by one intravenous infusion; followed by administration of 70 mg (session1) or 490mg (session2) GSK2398852 (unlabelled anti-SAP mAb) together with 10 mg of 89Zr-GSK2398852 (up to 37 megabecquerel of radioactive dose) via two separate intravenous infusion on Day 3. Participants also received a subcutaneous injection of GSK2315698 60 mg thrice daily for up to 8 days after administration of unlabelled anti-SAP mAb dose. Up to 3 PET scans were performed after the end of 89Zr-GSK2398852 infusion. There was a minimum of 4 weeks of duration between dosing sessions of anti-SAP mAb. | 2 |
| Part B: Anti-SAP Participants with either wild type or ATTR-CM were planned to undergo one dosing sessions. Participants were planned to be administered 200 mg/mL GSK2315698 via intravenous infusion for 48 hours followed by administration of 100 mg/mL GSK2398852 (unlabelled anti-SAP mAb) together with 10 mg of 89Zr-GSK2398852 (up to 37 megabecquerel of radioactive dose) via two separate intravenous infusion on Day 3. Participants were planned to receive a subcutaneous injection of GSK2315698 thrice daily for up to 8 days after administration of unlabelled anti-SAP mAb dose. Up to 2 PET scans were planned to be performed after the end of 89Zr-GSK2398852 infusion. | 0 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part A (up to 26 Days) | Study Closed/Terminated | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Part A: Anti-SAP |
|---|---|---|
| Age, Continuous | 77.5 Years STANDARD_DEVIATION 3.54 | 77.5 Years STANDARD_DEVIATION 3.54 |
| Race/Ethnicity, Customized White | 2 Participants | 2 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Part A- Session 1: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight.
Time frame: Session 1: Days 4, 5, 6 and 8
Population: All treated Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb | Session 1: Day 5, n=1 | 1.130 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb | Session 1: Day 6, n=1 | 1.320 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb | Session 1: Day 8, n=1 | 0.960 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb | Session 1: Day 4, n=2 | 2.470 Grams per milliliter | Standard Deviation 1.1738 |
Primary
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as blood pool left atrium, blood pool left ventricle, blood pool right ventricle, left ventricle wall - high uptake, left ventricle wall - low uptake, mid septum - high uptake and mid septum - low uptake. Peak SUV values derived from PET images has been presented. All treated population consisted of all participants who received at least one Anti-SAP treatment including 89Zr-GSK2398852.
Time frame: Session 1: Days 4, 5, 6 and 8
Population: All treated Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Blood pool left atrium,Day4,n=2 | 2.995 Grams per milliliter | Standard Deviation 1.4637 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Blood pool left atrium,Day5,n=1 | 0.550 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Blood pool left atrium,Day6,n=1 | 0.640 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Blood pool left atrium,Day8,n=1 | 0.400 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Blood pool left ventricle,Day4,n=2 | 2.800 Grams per milliliter | Standard Deviation 1.5274 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Blood pool left ventricle,Day5,n=1 | 0.510 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Blood pool left ventricle,Day6,n=1 | 0.850 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Blood pool left ventricle,Day8,n=1 | 0.430 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Blood pool right ventricle,Day4,n=2 | 3.165 Grams per milliliter | Standard Deviation 1.1526 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Blood pool right ventricle,Day5,n=1 | 1.050 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Blood pool right ventricle,Day6,n=1 | 0.950 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Blood pool right ventricle,Day8,n=1 | 1.240 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Left ventricle wall-high uptake,Day4,n=2 | 2.380 Grams per milliliter | Standard Deviation 1.4425 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Left ventricle wall-high uptake,Day5,n=1 | 1.290 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Left ventricle wall-high uptake,Day6,n=1 | 3.400 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Left ventricle wall-high uptake,Day8,n=1 | 1.440 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Left ventricle wall-low uptake,Day4,n=2 | 1.740 Grams per milliliter | Standard Deviation 1.4425 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Left ventricle wall-low uptake,Day5,n=1 | 0.700 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Left ventricle wall-low uptake,Day6,n=1 | 1.840 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1:Left ventricle wall-low uptake,Day8,n=1 | 0.760 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1: Mid septum-high uptake,Day4,n=2 | 2.335 Grams per milliliter | Standard Deviation 1.2516 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1: Mid septum-high uptake,Day5,n=1 | 1.420 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1: Mid septum-high uptake,Day6,n=1 | 2.880 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1: Mid septum-high uptake,Day8,n=1 | 1.520 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1: Mid septum-low uptake,Day4,n=2 | 1.955 Grams per milliliter | Standard Deviation 1.6051 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1: Mid septum-low uptake,Day5,n=1 | 0.780 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1: Mid septum-low uptake,Day6,n=1 | 2.230 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb | Session1: Mid septum-low uptake,Day8,n=1 | 0.610 Grams per milliliter | — |
Primary
Part A- Session 2: Mean SUV of Whole Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight.
Time frame: Session 2: Days 3, 4 and 5
Population: All treated Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Whole Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session 2: Day 3 | 7.090 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Whole Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session 2: Day 4 | 4.440 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Whole Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session 2: Day 5 | 3.390 Grams per milliliter |
Primary
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as blood pool left atrium, blood pool left ventricle, blood pool right ventricle, left ventricle wall - high uptake, left ventricle wall - low uptake, mid septum - high uptake and mid septum - low uptake. Peak SUV values derived from PET images has been presented.
Time frame: Session 2: Days 3, 4 and 5
Population: All treated Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Blood pool left atrium,Day3 | 10.290 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Blood pool left atrium,Day4 | 5.330 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Blood pool left atrium,Day5 | 3.550 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Blood pool left ventricle,Day3 | 10.120 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Blood pool left ventricle,Day4 | 4.910 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Blood pool left ventricle,Day5 | 3.110 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Blood pool right ventricle,Day3 | 10.390 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Blood pool right ventricle,Day4 | 5.160 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Blood pool right ventricle,Day5 | 3.500 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Left ventricle wall-high uptake,Day3 | 1.150 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Left ventricle wall-high uptake,Day4 | 4.540 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Left ventricle wall-high uptake,Day5 | 5.360 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Left ventricle wall-low uptake,Day3 | 3.110 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Left ventricle wall-low uptake,Day4 | 3.650 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Left ventricle wall-low uptake,Day5 | 3.980 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Mid septum-high uptake,Day3 | 4.680 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Mid septum-high uptake,Day4 | 4.200 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Mid septum-high uptake,Day5 | 4.780 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Mid septum-low uptake,Day3 | 3.580 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Mid septum-low uptake,Day4 | 3.570 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Mid septum-low uptake,Day5 | 3.800 Grams per milliliter |
Primary
Part B: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb
SUV of whole heart was planned to be measured.
Time frame: Days 3, 4 and 6
Population: All treated Population. Data was not collected as no participants were enrolled in Part B.
Primary
Part B: Mean SUV of Whole Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg
SUV of whole heart was planned to be measured.
Time frame: Days 3, 4 and 6
Population: All treated Population. Data was not collected as no participants were enrolled in Part B.
Primary
Part B: Peak SUV in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb
SUV in focal anatomical regions of the heart was planned to be measured.
Time frame: Days 3, 4 and 6
Population: All treated Population. Data was not collected as no participants were enrolled in Part B.
Primary
Part B: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg
SUV in focal anatomical regions of the heart was planned to be measured.
Time frame: Days 3, 4 and 6
Population: All treated Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part A:Area Under the Concentration Time Curve Till Last Observation (AUC[0 to t]) of Total mAb
Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).
Time frame: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A:Area Under the Concentration Time Curve Till Last Observation (AUC[0 to t]) of Total mAb | Session 1, n=2 | 471241.0 Hours*nanogram per milliliter |
| Part A: Anti-SAP- Session 1 | Part A:Area Under the Concentration Time Curve Till Last Observation (AUC[0 to t]) of Total mAb | Session 2, n=1 | 8274231.0 Hours*nanogram per milliliter |
Secondary
Part A: Area Under the Concentration Time Curve Till Time Infinity (AUC[0 to Infinity]) of Total mAb
Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).
Time frame: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Area Under the Concentration Time Curve Till Time Infinity (AUC[0 to Infinity]) of Total mAb | Session 1, n=2 | 487420.5 Hours*nanogram per milliliter |
| Part A: Anti-SAP- Session 1 | Part A: Area Under the Concentration Time Curve Till Time Infinity (AUC[0 to Infinity]) of Total mAb | Session 2, n=1 | 8696309.0 Hours*nanogram per milliliter |
Secondary
Part A: AUC(0 to Infinity) of 89Zr- GSK2398852 Radio-PK
Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.
Time frame: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: AUC(0 to Infinity) of 89Zr- GSK2398852 Radio-PK | Session 1, n=2 | 174764.0 Hours*Becquerel per gram |
| Part A: Anti-SAP- Session 1 | Part A: AUC(0 to Infinity) of 89Zr- GSK2398852 Radio-PK | Session 2, n=1 | 457666.0 Hours*Becquerel per gram |
Secondary
Part A: AUC(0 to t) of 89Zr- GSK2398852 Radio-PK
Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.
Time frame: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: AUC(0 to t) of 89Zr- GSK2398852 Radio-PK | Session 1, n=2 | 168044.5 Hours*Becquerel per gram |
| Part A: Anti-SAP- Session 1 | Part A: AUC(0 to t) of 89Zr- GSK2398852 Radio-PK | Session 2, n=1 | 386077.0 Hours*Becquerel per gram |
Secondary
Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP)
Blood samples were collected to analyze the troponin T and NT-ProBNP at indicated time points. Baseline was considered as the latest assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Session 1: Baseline (Day 1 Pre-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 26; Session 2: Day 1- Pre-dose, Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 26
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session1-Day2,n=2 | -6.45 Nanograms per liter | Standard Deviation 5.02 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session1-Day3,n=2 | -13.15 Nanograms per liter | Standard Deviation 13.93 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session1-Day4,n=2 | 2.40 Nanograms per liter | Standard Deviation 5.091 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session1-Day5,n=2 | -4.80 Nanograms per liter | Standard Deviation 3.111 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session1-Day6,n=2 | 0.80 Nanograms per liter | Standard Deviation 4.525 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session1-Day7,n=2 | -4.85 Nanograms per liter | Standard Deviation 3.041 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session1-Day8,n=2 | -1.45 Nanograms per liter | Standard Deviation 0.636 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session1-Day9,n=2 | -4.65 Nanograms per liter | Standard Deviation 3.323 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session1-Day10,n=2 | 17.00 Nanograms per liter | Standard Deviation 26.87 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session1-Day26,n=2 | -5.45 Nanograms per liter | Standard Deviation 5.02 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session2-Day1-pre-dose,n=1 | -2.10 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session2-Day2,n=1 | -4.40 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session2-Day3,n=1 | -2.80 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session2-Day4,n=1 | -2.90 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session2-Day5,n=1 | -3.00 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session2-Day6,n=1 | -3.70 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session2-Day7,n=1 | -2.20 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session2-Day8,n=1 | -3.30 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session2-Day9,n=1 | -2.60 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session2-Day10,n=1 | -2.00 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | Troponin T:Session2-Day26,n=1 | -3.60 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session1-Day2,n=2 | -525.0 Nanograms per liter | Standard Deviation 530.33 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session1-Day3,n=2 | -525.0 Nanograms per liter | Standard Deviation 502.05 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session1-Day4,n=2 | 835.0 Nanograms per liter | Standard Deviation 601.04 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session1-Day5,n=2 | -35.0 Nanograms per liter | Standard Deviation 7.07 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session1-Day6,n=2 | 360.0 Nanograms per liter | Standard Deviation 1004.09 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session1-Day7,n=2 | 470.0 Nanograms per liter | Standard Deviation 636.4 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session1-Day8,n=2 | 540.0 Nanograms per liter | Standard Deviation 579.83 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session1-Day9,n=2 | -90.0 Nanograms per liter | Standard Deviation 381.84 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session1-Day10,n=2 | 585.0 Nanograms per liter | Standard Deviation 1124.3 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session1-Day26,n=2 | 115.0 Nanograms per liter | Standard Deviation 558.61 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session2-Day1-pre-dose,n=1 | 20.0 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session2-Day2,n=1 | -80.0 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session2-Day3,n=1 | -240.0 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session2-Day4,n=1 | 280.0 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session2-Day5,n=1 | 60.0 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session2-Day6,n=1 | 1040.0 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session2-Day7,n=1 | 1030.0 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session2-Day8,n=1 | 400.0 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session2-Day9,n=1 | 120.0 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session2-Day10,n=1 | -40.0 Nanograms per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) | NT-ProBNP:Session2-Day26,n=1 | 0.0 Nanograms per liter | — |
Secondary
Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein
Blood samples were collected to analyze the chemistry parameters: Albumin and Protein. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 1: Albumin, Day 3, n=2 | -2.0 Grams per liter | Standard Deviation 1.41 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 1: Albumin, Day 5, n=2 | -2.0 Grams per liter | Standard Deviation 1.41 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 1: Albumin, Day 7, n=2 | -1.0 Grams per liter | Standard Deviation 2.83 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 1: Albumin, Day 10, n=2 | -2.0 Grams per liter | Standard Deviation 4.24 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 1: Albumin, Day 26, n=2 | 0.5 Grams per liter | Standard Deviation 3.54 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 2: Albumin, Day1-pre-dose, n=1 | -1.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 2: Albumin, Day 3, n=1 | -4.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 2: Albumin, Day 5, n=1 | -4.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 2: Albumin, Day 7, n=1 | -4.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 2: Albumin, Day 10, n=1 | -6.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 2: Albumin, Day 26, n=1 | -4.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 1: Protein, Day 3, n=2 | -2.5 Grams per liter | Standard Deviation 0.71 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 1: Protein, Day 5, n=2 | -6.0 Grams per liter | Standard Deviation 2.83 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 1: Protein, Day 7, n=2 | -3.0 Grams per liter | Standard Deviation 1.41 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 1: Protein, Day 10, n=1 | -8.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 1: Protein, Day 26, n=2 | 2.5 Grams per liter | Standard Deviation 9.19 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 2: Protein, Day1-pre-dose, n=1 | -3.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 2: Protein, Day 3, n=1 | -8.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 2: Protein, Day 7, n=1 | -5.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 2: Protein, Day 10, n=1 | -7.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein | Session 2: Protein, Day 26, n=1 | -5.0 Grams per liter | — |
Secondary
Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST)
Blood samples were collected to analyze the chemistry parameters: ALP, ALT and AST. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: ALP, Day 3, n=2 | -8.0984 International units per liter | Standard Deviation 5.51433 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: ALP, Day 5, n=2 | 0.2999 International units per liter | Standard Deviation 17.39135 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: ALP, Day 7, n=1 | 7.7984 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: ALP, Day 10, n=2 | -2.0996 International units per liter | Standard Deviation 2.96925 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: ALP, Day 26, n=2 | -2.3995 International units per liter | Standard Deviation 5.09015 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: ALP, Day1-pre-dose, n=1 | 4.1992 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: ALP, Day 3, n=1 | 1.7996 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: ALP, Day 5, n=1 | 2.9994 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: ALP, Day 7, n=1 | -1.7996 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: ALP, Day 10, n=1 | -0.5999 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: ALP, Day 26, n=1 | 0.5999 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: ALT, Day 3, n=2 | -1.7647 International units per liter | Standard Deviation 2.49569 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: ALT, Day 5, n=2 | -3.5294 International units per liter | Standard Deviation 4.99138 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: ALT, Day 7, n=2 | -0.2941 International units per liter | Standard Deviation 0.41595 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: ALT, Day 10, n=2 | 1.1765 International units per liter | Standard Deviation 1.66379 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: ALT, Day 26, n=2 | -2.9412 International units per liter | Standard Deviation 4.15948 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: ALT, Day1-pre-dose, n=1 | 0.0000 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: ALT, Day 3, n=1 | 0.0000 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: ALT, Day 5, n=1 | 0.0000 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: ALT, Day 7, n=1 | 0.0000 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: ALT, Day 10, n=1 | 0.0000 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: ALT, Day 26, n=1 | 0.0000 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: AST, Day 3, n=2 | -5.3989 International units per liter | Standard Deviation 4.24179 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: AST, Day 5, n=2 | -7.1986 International units per liter | Standard Deviation 7.63523 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: AST, Day 7, n=2 | -3.2993 International units per liter | Standard Deviation 1.27254 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: AST, Day 10, n=2 | -2.9994 International units per liter | Standard Deviation 0.84836 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 1: AST, Day 26, n=2 | -3.2993 International units per liter | Standard Deviation 5.51433 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: AST, Day1-pre-dose, n=1 | -0.5999 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: AST, Day 3, n=1 | -5.3989 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: AST, Day 5, n=1 | -4.7990 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: AST, Day 7, n=1 | -4.1992 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: AST, Day 10, n=1 | -5.3989 International units per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) | Session 2: AST, Day 26, n=1 | -4.1992 International units per liter | — |
Secondary
Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine
Blood samples were collected to analyze the chemistry parameters: Direct Bilirubin, Bilirubin, Creatinine. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Direct Bilirubin, Day 3, n=2 | -2.70 Micromoles per liter | Standard Deviation 2.121 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Direct Bilirubin, Day 5, n=2 | -4.35 Micromoles per liter | Standard Deviation 2.051 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Direct Bilirubin, Day 7, n=2 | -3.75 Micromoles per liter | Standard Deviation 3.323 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Direct Bilirubin, Day 10, n=2 | -2.80 Micromoles per liter | Standard Deviation 3.111 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Direct Bilirubin, Day 26, n=2 | -1.70 Micromoles per liter | Standard Deviation 0.707 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Direct Bilirubin, Day1-pre-dose, n=1 | 0.30 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Direct Bilirubin, Day 3, n=1 | -0.30 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Direct Bilirubin, Day 5, n=1 | 0.60 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Direct Bilirubin, Day 7, n=1 | 0.00 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Direct Bilirubin, Day 10, n=1 | -0.50 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Direct Bilirubin, Day 26, n=1 | -0.50 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Bilirubin, Day 3, n=2 | -9.30 Micromoles per liter | Standard Deviation 6.647 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Bilirubin, Day 5, n=2 | -12.30 Micromoles per liter | Standard Deviation 8.061 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Bilirubin, Day 7, n=2 | -11.85 Micromoles per liter | Standard Deviation 7.283 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Bilirubin, Day 10, n=2 | -9.55 Micromoles per liter | Standard Deviation 9.122 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Bilirubin, Day 26, n=2 | -5.10 Micromoles per liter | Standard Deviation 1.273 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Bilirubin, Day1-pre-dose, n=1 | 0.00 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Bilirubin, Day 3, n=1 | -2.00 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Bilirubin, Day 5, n=1 | 0.00 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Bilirubin, Day 7, n=1 | -1.20 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Bilirubin, Day 10, n=1 | -2.40 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Bilirubin, Day 26, n=1 | -2.70 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Creatinine, Day 3, n=2 | 6.5 Micromoles per liter | Standard Deviation 6.36 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Creatinine, Day 5, n=2 | -4.5 Micromoles per liter | Standard Deviation 2.12 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Creatinine, Day 7, n=2 | 1.0 Micromoles per liter | Standard Deviation 0 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Creatinine, Day 10, n=2 | 1.0 Micromoles per liter | Standard Deviation 9.9 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 1: Creatinine, Day 26, n=2 | 13.0 Micromoles per liter | Standard Deviation 1.41 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Creatinine, Day1-pre-dose, n=1 | -1.0 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Creatinine, Day 3, n=1 | 0.0 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Creatinine, Day 5, n=1 | -11.0 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Creatinine, Day 7, n=1 | 0.0 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Creatinine, Day 10, n=1 | 1.0 Micromoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine | Session 2: Creatinine, Day 26, n=1 | -2.0 Micromoles per liter | — |
Secondary
Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea
Blood samples were collected to analyze the chemistry parameters: Glucose, Calcium, Potassium, Sodium and Urea. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Glucose, Day 3, n=2 | -2.40 Millimoles per liter | Standard Deviation 3.253 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Glucose, Day 5, n=2 | -2.45 Millimoles per liter | Standard Deviation 4.455 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Glucose, Day 7, n=2 | -3.25 Millimoles per liter | Standard Deviation 5.303 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Glucose, Day 10, n=2 | -3.60 Millimoles per liter | Standard Deviation 2.404 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Glucose, Day 26, n=2 | -2.60 Millimoles per liter | Standard Deviation 2.97 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Glucose, Day1-pre-dose, n=1 | 1.10 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Glucose, Day 3, n=1 | -1.80 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Glucose, Day 5, n=1 | -1.70 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Glucose, Day 7, n=1 | -2.30 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Glucose, Day 10, n=1 | -1.80 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Glucose, Day 26, n=1 | 0.30 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Calcium, Day 3, n=2 | -0.050 Millimoles per liter | Standard Deviation 0.0141 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Calcium, Day 5, n=2 | -0.075 Millimoles per liter | Standard Deviation 0.0354 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Calcium, Day 7, n=1 | -0.090 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Calcium, Day 10, n=2 | -0.010 Millimoles per liter | Standard Deviation 0.1556 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Calcium, Day 26, n=2 | -0.030 Millimoles per liter | Standard Deviation 0.0424 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Calcium, Day1-pre-dose, n=1 | 0.020 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Calcium, Day 3, n=1 | -0.140 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Calcium, Day 5, n=1 | -0.030 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Calcium, Day 7, n=1 | -0.080 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Calcium, Day 10, n=1 | -0.040 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Calcium, Day 26, n=1 | 0.040 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Potassium, Day 3, n=2 | -0.10 Millimoles per liter | Standard Deviation 0.141 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Potassium, Day 5, n=2 | -0.10 Millimoles per liter | Standard Deviation 0.141 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Potassium, Day 7, n=1 | 0.00 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Potassium, Day 10, n=2 | -0.30 Millimoles per liter | Standard Deviation 0.141 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Potassium, Day 26, n=2 | -0.30 Millimoles per liter | Standard Deviation 0 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Potassium, Day1-pre-dose, n=1 | -0.10 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Potassium, Day 3, n=1 | -0.50 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Potassium, Day 5, n=1 | 0.10 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Potassium, Day 7, n=1 | -0.50 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Potassium, Day 10, n=1 | -0.40 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Potassium, Day 26, n=1 | -0.10 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Sodium, Day 3, n=2 | 3.0 Millimoles per liter | Standard Deviation 1.41 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Sodium, Day 5, n=2 | -0.5 Millimoles per liter | Standard Deviation 0.71 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Sodium, Day 7, n=2 | 2.0 Millimoles per liter | Standard Deviation 1.41 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Sodium, Day 10, n=2 | 3.5 Millimoles per liter | Standard Deviation 0.71 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Sodium, Day 26, n=2 | 0.5 Millimoles per liter | Standard Deviation 3.54 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Sodium, Day1-pre-dose, n=1 | 1.0 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Sodium, Day 3, n=1 | 4.0 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Sodium, Day 5, n=1 | 2.0 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Sodium, Day 7, n=1 | 1.0 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Sodium, Day 10, n=1 | 3.0 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Sodium, Day 26, n=1 | 0.0 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Urea, Day 3, n=2 | 0.85 Millimoles per liter | Standard Deviation 1.202 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Urea, Day 5, n=2 | 1.00 Millimoles per liter | Standard Deviation 3.111 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Urea, Day 7, n=2 | -0.25 Millimoles per liter | Standard Deviation 1.344 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Urea, Day 10, n=2 | -0.20 Millimoles per liter | Standard Deviation 0.707 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 1: Urea, Day 26, n=2 | 0.70 Millimoles per liter | Standard Deviation 1.273 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Urea, Day1-pre-dose, n=1 | -0.10 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Urea, Day 3, n=1 | 1.00 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Urea, Day 5, n=1 | 0.70 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Urea, Day 7, n=1 | 0.10 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Urea, Day 10, n=1 | 0.10 Millimoles per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Session 2: Urea, Day 26, n=1 | 0.10 Millimoles per liter | — |
Secondary
Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Session 1: Day 3, n=2 | 0.0 Picograms | Standard Deviation 0 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Session 1: Day 5, n=2 | 0.0 Picograms | Standard Deviation 0 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Session 1: Day 7, n=2 | 0.0 Picograms | Standard Deviation 0 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Session 1: Day 10, n=2 | 0.5 Picograms | Standard Deviation 0.71 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Session 1: Day 26, n=2 | 0.5 Picograms | Standard Deviation 0.71 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Session 2: Day1-pre-dose, n=1 | 0.0 Picograms | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Session 2: Day 3, n=1 | 0.0 Picograms | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Session 2: Day 5, n=1 | 0.0 Picograms | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Session 2: Day 7, n=1 | 1.0 Picograms | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Session 2: Day 10, n=1 | 0.0 Picograms | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Session 2: Day 26, n=1 | 0.0 Picograms | — |
Secondary
Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Volume. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Session 1: Day 26, n=2 | 0.60 Femtoliter | Standard Deviation 1.556 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Session 1: Day 3, n=2 | 0.75 Femtoliter | Standard Deviation 1.485 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Session 1: Day 5, n=2 | 0.90 Femtoliter | Standard Deviation 0.707 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Session 1: Day 7, n=2 | 1.85 Femtoliter | Standard Deviation 4.455 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Session 1: Day 10, n=2 | 0.45 Femtoliter | Standard Deviation 1.061 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Session 2: Day1-pre-dose, n=1 | -2.60 Femtoliter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Session 2: Day 3, n=1 | -2.50 Femtoliter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Session 2: Day 5, n=1 | -3.10 Femtoliter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Session 2: Day 7, n=1 | -0.90 Femtoliter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Session 2: Day 10, n=1 | 1.50 Femtoliter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Session 2: Day 26, n=1 | -0.90 Femtoliter | — |
Secondary
Part A: Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1-Pre-dose, Days 3, 5, 7, 10 and 26
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hematocrit | Session 1: Day 10, n=2 | -0.020 Percentage of red blood cells in blood | Standard Deviation 0.0283 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hematocrit | Session 1: Day 26, n=2 | -0.015 Percentage of red blood cells in blood | Standard Deviation 0.0212 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hematocrit | Session 2: Day1-pre-dose, n=1 | -0.040 Percentage of red blood cells in blood | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hematocrit | Session 2: Day 3, n=1 | -0.040 Percentage of red blood cells in blood | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hematocrit | Session 2: Day 5, n=1 | -0.040 Percentage of red blood cells in blood | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hematocrit | Session 2: Day 7, n=1 | -0.050 Percentage of red blood cells in blood | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hematocrit | Session 2: Day 10, n=1 | -0.040 Percentage of red blood cells in blood | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hematocrit | Session 2: Day 26, n=1 | -0.050 Percentage of red blood cells in blood | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hematocrit | Session 1: Day 3, n=2 | -0.015 Percentage of red blood cells in blood | Standard Deviation 0.0071 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hematocrit | Session 1: Day 5, n=2 | -0.025 Percentage of red blood cells in blood | Standard Deviation 0.0071 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hematocrit | Session 1: Day 7, n=2 | -0.010 Percentage of red blood cells in blood | Standard Deviation 0.0283 |
Secondary
Part A: Change From Baseline in Hematology Parameter: Hemoglobin
Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hemoglobin | Session 2: Day 5, n=1 | -11.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hemoglobin | Session 2: Day 7, n=1 | -14.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hemoglobin | Session 1: Day 3, n=2 | -6.5 Grams per liter | Standard Deviation 2.12 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hemoglobin | Session 1: Day 5, n=2 | -10.5 Grams per liter | Standard Deviation 3.54 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hemoglobin | Session 1: Day 7, n=2 | -6.5 Grams per liter | Standard Deviation 3.54 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hemoglobin | Session 1: Day 10, n=2 | -8.0 Grams per liter | Standard Deviation 5.66 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hemoglobin | Session 1: Day 26, n=2 | -5.5 Grams per liter | Standard Deviation 2.12 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hemoglobin | Session 2: Day1-pre-dose, n=1 | -9.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hemoglobin | Session 2: Day 3, n=1 | -12.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hemoglobin | Session 2: Day 10, n=1 | -15.0 Grams per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameter: Hemoglobin | Session 2: Day 26, n=1 | -17.0 Grams per liter | — |
Secondary
Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1-Pre-dose, Days 3, 5, 7, 10 and 26
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Basophils, Day 3, n=2 | 0.000 Billion cells per liter | Standard Deviation 0.0141 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Basophils, Day 5, n=2 | -0.010 Billion cells per liter | Standard Deviation 0 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Basophils, Day 7, n=2 | -0.015 Billion cells per liter | Standard Deviation 0.0071 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Basophils, Day 10, n=2 | -0.015 Billion cells per liter | Standard Deviation 0.0071 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Basophils, Day 26, n=2 | -0.005 Billion cells per liter | Standard Deviation 0.0071 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Basophils, Day1-pre-dose, n=1 | -0.010 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Basophils, Day 3, n=1 | -0.010 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Basophils, Day 5, n=1 | -0.020 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Basophils, Day 7, n=1 | -0.010 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Basophils, Day 10, n=1 | 0.000 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Basophils, Day 26, n=1 | -0.010 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Eosinophils, Day 3, n=2 | -0.025 Billion cells per liter | Standard Deviation 0.3182 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Eosinophils, Day 5, n=2 | 0.050 Billion cells per liter | Standard Deviation 0.2121 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Eosinophils, Day 7, n=2 | 0.000 Billion cells per liter | Standard Deviation 0.1414 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Eosinophils, Day 10, n=2 | 0.000 Billion cells per liter | Standard Deviation 0.1414 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Eosinophils, Day 26, n=2 | 0.050 Billion cells per liter | Standard Deviation 0.3536 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Eosinophils, Day1-pre-dose, n=1 | -0.100 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Eosinophils, Day 3, n=1 | -0.100 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Eosinophils, Day 5, n=1 | -0.200 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Eosinophils, Day 7, n=1 | -0.100 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Eosinophils, Day 10, n=1 | -0.100 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Eosinophils, Day 26, n=1 | -0.230 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Lymphocytes, Day 3, n=2 | -0.05 Billion cells per liter | Standard Deviation 0.636 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Lymphocytes, Day 5, n=2 | 0.30 Billion cells per liter | Standard Deviation 0.141 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Lymphocytes, Day 7, n=2 | 0.05 Billion cells per liter | Standard Deviation 0.212 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Lymphocytes, Day 10, n=2 | -0.20 Billion cells per liter | Standard Deviation 0.424 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Lymphocytes, Day 26, n=2 | -0.10 Billion cells per liter | Standard Deviation 0.849 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Lymphocytes, Day1-pre-dose, n=1 | -0.30 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Lymphocytes, Day 3, n=1 | -0.30 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Lymphocytes, Day 5, n=1 | -0.20 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Lymphocytes, Day 7, n=1 | 0.30 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Lymphocytes, Day 10, n=1 | -0.40 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Lymphocytes, Day 26, n=1 | -0.80 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Monocytes, Day 3, n=2 | 0.15 Billion cells per liter | Standard Deviation 0.212 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Monocytes, Day 5, n=2 | 0.10 Billion cells per liter | Standard Deviation 0 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Monocytes, Day 7, n=2 | 0.15 Billion cells per liter | Standard Deviation 0.212 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Monocytes, Day 10, n=2 | 0.15 Billion cells per liter | Standard Deviation 0.212 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Monocytes, Day 26, n=2 | 0.20 Billion cells per liter | Standard Deviation 0.141 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Monocytes, Day1-pre-dose, n=1 | 0.00 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Monocytes, Day 3, n=1 | 0.00 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Monocytes, Day 5, n=1 | 0.00 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Monocytes, Day 7, n=1 | 0.00 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Monocytes, Day 10, n=1 | 0.00 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Monocytes, Day 26, n=1 | -0.10 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Neutrophils, Day 3, n=2 | 0.20 Billion cells per liter | Standard Deviation 0.707 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Neutrophils, Day 5, n=2 | 0.45 Billion cells per liter | Standard Deviation 1.202 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Neutrophils, Day 7, n=2 | 0.00 Billion cells per liter | Standard Deviation 0 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Neutrophils, Day 10, n=2 | -0.05 Billion cells per liter | Standard Deviation 0.212 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Neutrophils, Day 26, n=2 | 0.05 Billion cells per liter | Standard Deviation 0.354 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Neutrophils, Day1-pre-dose, n=1 | -0.70 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Neutrophils, Day 3, n=1 | -1.20 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Neutrophils, Day 5, n=1 | 0.00 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Neutrophils, Day 7, n=1 | -0.70 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Neutrophils, Day 10, n=1 | -1.00 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Neutrophils, Day 26, n=1 | 0.40 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Platelets, Day 3, n=2 | -7.5 Billion cells per liter | Standard Deviation 4.95 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Platelets, Day 5, n=2 | -29.5 Billion cells per liter | Standard Deviation 23.33 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Platelets, Day 7, n=2 | -21.0 Billion cells per liter | Standard Deviation 4.24 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Platelets, Day 10, n=2 | -13.0 Billion cells per liter | Standard Deviation 1.41 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 1: Platelets, Day 26, n=2 | 12.0 Billion cells per liter | Standard Deviation 14.14 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Platelets, Day1-pre-dose, n=1 | -5.0 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Platelets, Day 3, n=1 | -32.0 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Platelets, Day 5, n=1 | -27.0 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Platelets, Day 7, n=1 | -31.0 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Platelets, Day 10, n=1 | -33.0 Billion cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Session 2: Platelets, Day 26, n=1 | -9.0 Billion cells per liter | — |
Secondary
Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes
Blood samples were collected to analyze the hematology parameters: Erythrocytes and Reticulocytes. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 2: Erythrocytes, Day 5, n=1 | -0.290 10^12 cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 2: Erythrocytes, Day 7, n=1 | -0.480 10^12 cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 1: Erythrocytes, Day 3, n=2 | -0.175 10^12 cells per liter | Standard Deviation 0.0212 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 1: Erythrocytes, Day 5, n=2 | -0.295 10^12 cells per liter | Standard Deviation 0.1485 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 1: Erythrocytes, Day 7, n=2 | -0.180 10^12 cells per liter | Standard Deviation 0.1556 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 1: Erythrocytes, Day 10, n=2 | -0.230 10^12 cells per liter | Standard Deviation 0.2687 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 1: Erythrocytes, Day 26, n=2 | -0.200 10^12 cells per liter | Standard Deviation 0.1273 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 2: Erythrocytes, Day1-Pre-dose, n=1 | -0.270 10^12 cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 2: Erythrocytes, Day 3, n=1 | -0.340 10^12 cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 2: Erythrocytes, Day 10, n=1 | -0.480 10^12 cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 2: Erythrocytes, Day 26, n=1 | -0.470 10^12 cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 1: Reticulocytes, Day 3, n=2 | -0.0085 10^12 cells per liter | Standard Deviation 0.00212 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 1: Reticulocytes, Day 5, n=2 | -0.0085 10^12 cells per liter | Standard Deviation 0.00636 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 1: Reticulocytes, Day 7, n=2 | -0.0075 10^12 cells per liter | Standard Deviation 0.00778 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 1: Reticulocytes, Day 10, n=2 | -0.0065 10^12 cells per liter | Standard Deviation 0.00919 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 1: Reticulocytes, Day 26, n=2 | -0.0035 10^12 cells per liter | Standard Deviation 0.01061 |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 2: Reticulocytes, Day1-pre-dose, n=1 | -0.0100 10^12 cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 2: Reticulocytes, Day 3, n=1 | -0.0180 10^12 cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 2: Reticulocytes, Day 5, n=1 | -0.0140 10^12 cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 2: Reticulocytes, Day 7, n=1 | -0.0100 10^12 cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 2: Reticulocytes, Day 10, n=1 | -0.0170 10^12 cells per liter | — |
| Part A: Anti-SAP- Session 1 | Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Session 2: Reticulocytes, Day 26, n=1 | -0.0030 10^12 cells per liter | — |
Secondary
Part A: Clearance of Total mAb
Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).
Time frame: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Clearance of Total mAb | Session 1, n=2 | NA Liters per hour |
| Part A: Anti-SAP- Session 1 | Part A: Clearance of Total mAb | Session 2, n=1 | NA Liters per hour |
Secondary
Part A: Cmax of 89Zr-GSK2398852 PKs of Radioactivity (Radio-PK)
Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.
Time frame: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Cmax of 89Zr-GSK2398852 PKs of Radioactivity (Radio-PK) | Session 1, n=2 | 9240.5 Becquerel per gram |
| Part A: Anti-SAP- Session 1 | Part A: Cmax of 89Zr-GSK2398852 PKs of Radioactivity (Radio-PK) | Session 2, n=1 | 11923.0 Becquerel per gram |
Secondary
Part A: Maximum Concentration in Plasma (Cmax) of Total mAb
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852). PK Population consisted of all participants from the All Treated Population for whom a PK sample was obtained and analyzed.
Time frame: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Maximum Concentration in Plasma (Cmax) of Total mAb | Session 1, n=2 | 18061.0 Nanograms per milliliter |
| Part A: Anti-SAP- Session 1 | Part A: Maximum Concentration in Plasma (Cmax) of Total mAb | Session 2, n=1 | 226994.0 Nanograms per milliliter |
Secondary
Part A: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings
12-lead ECGs were measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time frame: Up to Day 26 of the last session
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | CS | 0 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | NCS | 2 Participants |
Secondary
Part A: Number of Participants With Abnormal Inpatient Cardiac Telemetry
Continuous inpatient cardiac monitoring was performed via remote cardiac telemetry device. Abnormal findings were categorized as CS and NCS. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time frame: Up to Day 26 of the last session
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Abnormal Inpatient Cardiac Telemetry | CS | 0 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Abnormal Inpatient Cardiac Telemetry | NCS | 2 Participants |
Secondary
Part A: Number of Participants With Abnormal Outpatient Cardiac Telemetry
Continuous outpatient cardiac monitoring was performed via remote cardiac bodyguardian telemetry device. Abnormal findings were categorized as CS and NCS. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time frame: Up to Day 26 of the last session
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Abnormal Outpatient Cardiac Telemetry | CS | 0 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Abnormal Outpatient Cardiac Telemetry | NCS | 2 Participants |
Secondary
Part A: Number of Participants With Abnormal Pulse Rate
Pulse rate were measured in a semi-supine position after 5 minutes of rest for the participant. PCI range for the pulse rate was as follows: pulse rate- \<35 and \>140 beats per minute (bpm).
Time frame: Up to Day 26 of the last session
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Abnormal Pulse Rate | 0 Participants |
Secondary
Part A: Number of Participants With Abnormal Respiratory Rate
Respiratory rate was measured in a semi-supine position after 5 minutes of rest for the participant. Normal range for the respiratory rate was as follows: respiratory rate- \<12 and \>25 breaths per minute.
Time frame: Up to Day 26 of the last session
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Abnormal Respiratory Rate | 0 Participants |
Secondary
Part A: Number of Participants With Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP and DBP were measured in a semi-supine position after 5 minutes of rest for the participant. Potential Clinical Importance (PCI) ranges for the SBP and DBP were as follows: SBP- \<90 and \>180 millimeters of mercury (mmHg), and DBP- \<30 and \>110 mmHg.
Time frame: Up to Day 26 of the last session
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 0 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 0 Participants |
Secondary
Part A: Number of Participants With Abnormal Temperature
Temperature was measured in a semi-supine position after 5 minutes of rest for the participant. Normal range for temperature was as follows: temperature- \>37.5 degree celsius.
Time frame: Up to Day 26 of the last session
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Abnormal Temperature | 0 Participants |
Secondary
Part A: Number of Participants With Abnormal Urinalysis Parameters: Glucose, Protein, Blood, Ketones
Urine samples were collected to analyze urinalysis parameters including glucose, protein, blood and ketones.
Time frame: Up to Day 26 of the last session
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Abnormal Urinalysis Parameters: Glucose, Protein, Blood, Ketones | 2 Participants |
Secondary
Part A: Number of Participants With Abnormal Urinalysis Parameters: Specific Gravity, Potential of Hydrogen
Urine samples were collected to analyze urinalysis parameters including specific gravity and potential of hydrogen.
Time frame: Up to Day 26 of the last session
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Abnormal Urinalysis Parameters: Specific Gravity, Potential of Hydrogen | 0 Participants |
Secondary
Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events which may require medical or surgical intervention. Safety Population consisted of all participants who received at least one dose of GSK2315698, GSK2398852 or 89Zr-GSK2398852.
Time frame: Up to Day 26 of the last session
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Secondary
Part A: Number of Participants With Cardiac Adverse Events
The number of participants with any cardiovascular AEs i.e. any AE coded to the cardiovascular system organ class are presented.
Time frame: Up to Day 26 of the last session
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Cardiac Adverse Events | 0 Participants |
Secondary
Part A: Number of Participants With Infusion Related Reactions
Number of participants with any infusion related reactions are presented.
Time frame: Up to Day 26 of the last session
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Infusion Related Reactions | 0 Participants |
Secondary
Part A: Number of Participants With New Abnormal Physical Examination Findings
A full and brief physical examination was performed, including assessments of the skin, lungs, cardiovascular system and abdomen (liver and spleen).
Time frame: Session 1: At screening (within 35 days of Anti-SAP treatment of session 1), Day 1 Pre-dose, Day 3, Day 5, Day 8 and Day 11; Session 2: Day 1 Pre-dose, Day 3, Day 5, Day 8 and Day 11
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With New Abnormal Physical Examination Findings | Session 1:Screening,n=2 | 1 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With New Abnormal Physical Examination Findings | Session1:Day 1 Pre-dose,n=2 | 2 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With New Abnormal Physical Examination Findings | Session1:Day 3,n=2 | 0 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With New Abnormal Physical Examination Findings | Session 1:Day 5,n=2 | 1 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With New Abnormal Physical Examination Findings | Session1:Day 8,n=2 | 0 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With New Abnormal Physical Examination Findings | Session1:Day 11,n=2 | 0 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With New Abnormal Physical Examination Findings | Session2:Day 1 Pre-dose,n=1 | 0 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With New Abnormal Physical Examination Findings | Session2:Day 3,n=1 | 0 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With New Abnormal Physical Examination Findings | Session2:Day 5,n=1 | 1 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With New Abnormal Physical Examination Findings | Session2:Day 8,n=1 | 0 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With New Abnormal Physical Examination Findings | Session2:Day 11,n=1 | 0 Participants |
Secondary
Part A: Number of Participants With Skin Rashes
Rash was graded as Grade 1 to Grade 4 based on symptoms and body surface area (BSA) affected; Grade 1: \<10 percent (%) BSA and asymptomatic; Grade 2: 10-30% BSA and/or mild symptoms (pain, itch and burning); Grade 3: \>30% BSA and/or moderate/severe symptoms (pain, itch and burning); and Grade 4: any rash with mucosal or systemic involvement (such as evidence of renal involvement).
Time frame: Up to Day 26 of the last session
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Skin Rashes | Grade 1 | 0 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Skin Rashes | Grade 2 | 1 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Skin Rashes | Grade 3 | 0 Participants |
| Part A: Anti-SAP- Session 1 | Part A: Number of Participants With Skin Rashes | Grade 4 | 0 Participants |
Secondary
Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as abdominal skin and skin of the back. Mean SUV derived from PET images has been presented.
Time frame: Session 1: Days 4, 5, 6 and 8
Population: All treated Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Abdominal skin,Day 4,n=2 | 0.325 Grams per milliliter | Standard Deviation 0.2475 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Abdominal skin,Day 5,n=1 | 0.080 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Abdominal skin,Day 6,n=1 | 0.940 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Abdominal skin,Day 8,n=1 | 0.140 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Skin of the back,Day 4,n=2 | 0.125 Grams per milliliter | Standard Deviation 0.1061 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Skin of the back,Day 5,n=1 | 0.060 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Skin of the back,Day 6,n=1 | 0.230 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Skin of the back,Day 8,n=1 | 0.100 Grams per milliliter | — |
Secondary
Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyriod Gland-goitre Hotspot
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for thyroid gland-goitre hotspot. Mean SUV derived from PET images has been presented.
Time frame: Session 1: Days 4 and 6
Population: All treated Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyriod Gland-goitre Hotspot | Session 1: Day 4 | 4.670 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyriod Gland-goitre Hotspot | Session 1: Day 6 | 4.240 Grams per milliliter |
Secondary
Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as adrenal gland, aorta, bone marrow, kidney, liver, spleen, abdominal region, brain, lung, parotid gland, and thigh. Mean SUV derived from PET images has been presented.
Time frame: Session 1: Days 4, 5, 6 and 8
Population: All treated Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Adrenal gland,Day 4,n=2 | 11.665 Grams per milliliter | Standard Deviation 1.9304 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Adrenal gland,Day 5,n=1 | 10.770 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Adrenal gland,Day 6,n=1 | 12.020 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Adrenal gland,Day 8,n=1 | 10.900 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Aorta,Day 4,n=2 | 2.580 Grams per milliliter | Standard Deviation 1.3859 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Aorta,Day 5,n=1 | 0.360 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Aorta,Day 6,n=1 | 0.500 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Aorta,Day 8,n=1 | 0.650 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Bone marrow,Day 4,n=2 | 3.015 Grams per milliliter | Standard Deviation 0.799 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Bone marrow,Day 5,n=1 | 3.170 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Bone marrow,Day 6,n=1 | 2.210 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Bone marrow,Day 8,n=1 | 3.880 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Kidney,Day 4,n=2 | 4.910 Grams per milliliter | Standard Deviation 1.1738 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Kidney,Day 5,n=1 | 5.130 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Kidney,Day 6,n=1 | 3.840 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Kidney,Day 8,n=1 | 4.820 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Liver,Day 4,n=2 | 17.805 Grams per milliliter | Standard Deviation 6.8519 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Liver,Day 5,n=1 | 25.560 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Liver,Day 6,n=1 | 16.940 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Liver,Day 8,n=1 | 24.800 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Spleen,Day 4,n=2 | 11.425 Grams per milliliter | Standard Deviation 2.2981 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Spleen,Day 5,n=1 | 11.050 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Spleen,Day 6,n=1 | 10.060 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Spleen,Day 8,n=1 | 11.340 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Abdominal region,Day 4,n=2 | 1.070 Grams per milliliter | Standard Deviation 0.5374 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Abdominal region,Day 5,n=1 | 0.610 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Abdominal region,Day 6,n=1 | 1.740 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Abdominal region,Day 8,n=1 | 0.460 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Brain,Day 4,n=2 | 0.125 Grams per milliliter | Standard Deviation 0.0354 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Brain,Day 5,n=1 | 0.060 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Brain,Day 6,n=1 | 0.070 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Brain,Day 8,n=1 | 0.070 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Lung,Day 4,n=2 | 0.555 Grams per milliliter | Standard Deviation 0.1202 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Lung,Day 5,n=1 | 0.440 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Lung,Day 6,n=1 | 0.260 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Lung,Day 8,n=1 | 0.400 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Parotid gland,Day 4,n=2 | 0.570 Grams per milliliter | Standard Deviation 0.297 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Parotid gland,Day 5,n=1 | 0.240 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Parotid gland,Day 6,n=1 | 0.580 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1:Parotid gland,Day 8,n=1 | 0.170 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Thigh,Day 4,n=2 | 0.260 Grams per milliliter | Standard Deviation 0.1131 |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Thigh,Day 5,n=1 | 0.110 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Thigh,Day 6,n=1 | 0.200 Grams per milliliter | — |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb | Session1: Thigh,Day 8,n=1 | 0.110 Grams per milliliter | — |
Secondary
Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Testes
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for testes. Mean SUV derived from PET images has been presented.
Time frame: Session 1: Days 4, 5 and 8
Population: All treated Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Testes | Session1: Day 4 | 5.400 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Testes | Session1: Day 5 | 5.520 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Testes | Session1: Day 8 | 5.670 Grams per milliliter |
Secondary
Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyroid Gland-goitre
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for thyroid gland-goitre. Mean SUV derived from PET images has been presented.
Time frame: Session 1: Days 4 and 6
Population: All treated Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyroid Gland-goitre | Session1: Day 6 | 1.390 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyroid Gland-goitre | Session1: Day 4 | 1.630 Grams per milliliter |
Secondary
Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as thyroid gland-goitre hotspot, abdominal skin and skin of the back. Mean SUV derived from PET images has been presented.
Time frame: Session 2: Days 3, 4 and 5
Population: All treated Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Thyroid gland-goitre hotspot,Day 3 | 1.890 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Thyroid gland-goitre hotspot,Day 4 | 3.690 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Thyroid gland-goitre hotspot,Day 5 | 3.190 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Abdominal skin,Day 3 | 0.620 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Abdominal skin,Day 4 | 0.780 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Abdominal skin,Day 5 | 0.870 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Skin of the back,Day 3 | 0.220 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Skin of the back,Day 4 | 0.250 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Skin of the back,Day 5 | 0.330 Grams per milliliter |
Secondary
Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as adrenal gland, aorta, bone marrow, kidney, liver, spleen, abdominal region, brain, lung, parotid gland, thigh, and thyroid gland- goitre. Mean SUV derived from PET images has been presented.
Time frame: Session 2: Days 3, 4, and 5
Population: All treated Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Adrenal gland,Day 3 | 4.800 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Adrenal gland,Day 4 | 8.380 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Adrenal gland,Day 5 | 6.360 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Aorta,Day 3 | 10.000 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Aorta,Day 4 | 5.890 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Aorta,Day 5 | 3.310 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Bone marrow,Day 3 | 1.860 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Bone marrow,Day 4 | 1.910 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Bone marrow,Day 5 | 1.410 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Kidney,Day 3 | 2.700 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Kidney,Day 4 | 3.260 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Kidney,Day 5 | 2.890 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Liver,Day 3 | 4.770 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Liver,Day 4 | 7.560 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Liver,Day 5 | 8.340 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Spleen,Day 3 | 4.440 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Spleen,Day 4 | 5.140 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Spleen,Day 5 | 5.440 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Abdominal region,Day 3 | 0.900 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Abdominal region,Day 4 | 2.170 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Abdominal region,Day 5 | 2.370 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Brain,Day 3 | 0.370 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Brain,Day 4 | 0.210 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Brain,Day 5 | 0.110 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Lung,Day 3 | 1.230 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Lung,Day 4 | 0.930 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Lung,Day 5 | 0.790 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Parotid gland,Day 3 | 1.550 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Parotid gland,Day 4 | 1.180 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Parotid gland,Day 5 | 0.850 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Thigh,Day 3 | 0.630 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Thigh,Day 4 | 0.530 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2: Thigh,Day 5 | 0.330 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Thyroid gland-goitre,Day 3 | 1.870 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Thyroid gland-goitre,Day 4 | 2.090 Grams per milliliter |
| Part A: Anti-SAP- Session 1 | Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg | Session2:Thyroid gland-goitre,Day 5 | 1.950 Grams per milliliter |
Secondary
Part A: T1/2 of 89Zr- GSK2398852 Radio-PK
Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.
Time frame: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: T1/2 of 89Zr- GSK2398852 Radio-PK | Session 2, n=1 | 26.70 Hours |
| Part A: Anti-SAP- Session 1 | Part A: T1/2 of 89Zr- GSK2398852 Radio-PK | Session 1, n=2 | 14.50 Hours |
Secondary
Part A: Terminal Half-life (T1/2) of Total mAb
Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).
Time frame: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Terminal Half-life (T1/2) of Total mAb | Session 1, n=2 | 17.70 Hours |
| Part A: Anti-SAP- Session 1 | Part A: Terminal Half-life (T1/2) of Total mAb | Session 2, n=1 | 23.10 Hours |
Secondary
Part A: Time Associated With Cmax (Tmax) of Total mAb
Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).
Time frame: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Time Associated With Cmax (Tmax) of Total mAb | Session 1, n=2 | 3.010 Hours |
| Part A: Anti-SAP- Session 1 | Part A: Time Associated With Cmax (Tmax) of Total mAb | Session 2, n=1 | 6.100 Hours |
Secondary
Part A: Tmax of 89Zr- GSK2398852 Radio-PK
Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.
Time frame: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Anti-SAP- Session 1 | Part A: Tmax of 89Zr- GSK2398852 Radio-PK | Session 1, n=2 | 1.160 Hours |
| Part A: Anti-SAP- Session 1 | Part A: Tmax of 89Zr- GSK2398852 Radio-PK | Session 2, n=1 | 1.100 Hours |
Secondary
Part B: AUC(0 to Infinity) of 89Zr- GSK2398852 Radio-PK
Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.
Time frame: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: AUC(0 to Infinity) of Total mAb
Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.
Time frame: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: AUC(0 to t) of 89Zr- GSK2398852 Radio-PK
Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.
Time frame: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: AUC(0 to t) of Total mAb
Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.
Time frame: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Change From Baseline in Cardiac Troponin T and NT-ProBNP
Blood samples were planned to be collected to analyze the troponin T and NT-ProBNP at indicated time points. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline and up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Change From Baseline in Chemistry Parameters: Albumin, Protein
Blood samples were planned to be collected to analyze the chemistry parameters.
Time frame: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Change From Baseline in Chemistry Parameters: ALP, ALT, AST
Blood samples were planned to be collected to analyze the chemistry parameters.
Time frame: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine
Blood samples were planned to be collected to analyze the chemistry parameters.
Time frame: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea
Blood samples were planned to be collected to analyze the chemistry parameters.
Time frame: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Blood samples were planned to be collected to analyze the hematology parameter.
Time frame: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Blood samples were planned to be collected to analyze the hematology parameter.
Time frame: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were planned to be collected to analyze the hematology parameter.
Time frame: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Change From Baseline in Hematology Parameter: Hemoglobin
Blood samples were planned to be collected to analyze the hematology parameter.
Time frame: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Blood samples were planned to be collected to analyze the hematology parameters.
Time frame: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes
Blood samples were planned to be collected to analyze the hematology parameters.
Time frame: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Clearance of Total mAb
Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.
Time frame: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Cmax of 89Zr-GSK2398852 Radio-PK
Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.
Time frame: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Cmax of Total mAb
Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.
Time frame: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb
SUV of focal radioactivity uptake for different organs/tissues was planned to be measured.
Time frame: Days 3, 4 and 6
Population: All treated Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg
SUV of focal radioactivity uptake for different organs/tissues was planned to be measured.
Time frame: Days 3, 4 and 6
Population: All treated Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb
SUV of total radioactivity uptake for different organs/tissues was planned to be measured.
Time frame: Days 3, 4 and 6
Population: All treated Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Mean SUV of Total Radioactivity Uptake After an Anti-SAP mAb Dose Between 200 mg and <=500 mg
SUV of total radioactivity uptake for different organs/tissues was planned to be measured.
Time frame: Days 3, 4 and 6
Population: All treated Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With Abnormal 12-lead ECG Findings
12-lead ECGs were planned to be measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant.
Time frame: Up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With Abnormal Inpatient Cardiac Telemetry
Continuous inpatient cardiac monitoring was planned to be performed via remote cardiac telemetry device.
Time frame: Up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With Abnormal Outpatient Cardiac Telemetry
Continuous outpatient cardiac monitoring was planned to be performed via remote cardiac bodyguardian telemetry device.
Time frame: Up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With Abnormal Pulse Rate
Pulse rate was planned to be measured in a semi-supine position after 5 minutes of rest for the participant.
Time frame: Up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With Abnormal Respiratory Rate
Respiratory rate was planned to be measured in a semi-supine position after 5 minutes of rest for the participant.
Time frame: Up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With Abnormal SBP and DBP
SBP and DBP were planned to be measured in a semi-supine position after 5 minutes of rest for the participant.
Time frame: Up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With Abnormal Temperature
Temperature was planned to be measured in a semi-supine position after 5 minutes of rest for the participant.
Time frame: Up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With Abnormal Urinalysis Parameters: Glucose, Protein, Blood, Ketones
Urine samples were planned to be collected to analyze the urinalysis parameters.
Time frame: Up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With Abnormal Urinalysis Parameters: Specific Gravity, Potential of Hydrogen
Urine samples were planned to be collected to analyze the urinalysis parameters.
Time frame: Up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With AEs and SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events which may require medical or surgical intervention.
Time frame: Up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With Cardiac Adverse Events
The number of participants with any cardiovascular AEs i.e. any AE coded to the cardiovascular system organ class were planned to be reported.
Time frame: Up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With Infusion Related Reactions
Number of participants with any infusion related reactions were planned to be reported.
Time frame: Up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With New Abnormal Physical Examination Findings
A full and brief physical examination was planned to be performed, including assessments of the skin, lungs, cardiovascular system and abdomen (liver and spleen).
Time frame: At screening (within 35 days of Anti-SAP treatment), Days 1, 3, 5, 8 and 11
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Number of Participants With Skin Rashes
Rash was planned to be graded as Grade 1 to Grade 4 based on symptoms and BSA affected; Grade 1: \<10% BSA and asymptomatic; Grade 2: 10-30% BSA and/or mild symptoms (pain, itch and burning); Grade 3: \>30% BSA and/or moderate/severe symptoms (pain, itch and burning); and Grade 4: any rash with mucosal or systemic involvement (such as evidence of renal involvement).
Time frame: Up to Day 26
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: T1/2 of 89Zr- GSK2398852 Radio-PK
Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.
Time frame: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: T1/2 of Total mAb
Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.
Time frame: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Tmax of 89Zr-GSK2398852 Radio-PK
Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.
Time frame: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Tmax of Total mAb
Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.
Time frame: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8
Population: PK Population. Data was not collected as no participants were enrolled in Part B.