Relapsing Multiple Sclerosis
Conditions
Brief summary
This study (28851) is a long-term follow-up study of subjects enrolled in ATAMS study 28063 (NCT00642902). The aim of this study is to monitor the safety and tolerability of atacicept administered for up to 5 years to subjects with relapsing multiple sclerosis (RMS). This extension study consists of two parts. Part A will be double blind and Part B will be open label. During Part A, subjects initially randomized to atacicept will continue to receive the atacicept dose to which they have been randomized in study 28063 (ATAMS) once a week subcutaneously (under the skin). Subjects randomized to placebo in ATAMS will receive atacicept at 150 mg once a week subcutaneously during Part A. Once the results of ATAMS are available and the atacicept dose with the best benefit / risk ratio has been identified, all subjects will be switched to this dose and will continue the extension study open-label (Part B). Throughout the study, subjects and investigators will remain blinded with respect to initial and part A treatment allocation/dose.
Interventions
DRUGAtacicept 25 mg
Subjects who received atacicept 25 milligram (mg) subcutaneously (SC) as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study will continue with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
DRUGAtacicept 75 mg
Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study will continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
DRUGAtacicept 150 mg
Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study will continue with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Participation in study 28063. * Completion of Week 36 visit of the core study 28063. * Willingness and ability to comply with study procedures for the duration of the study. * Voluntary provision of written informed consent (including, for the USA, subject authorization under the Health Insurance Portability and Accountability Act (HIPAA)), given before any study-related procedure that is not part of normal medical care and with the understanding that the subject may withdraw consent at any time without prejudice to his or her future medical care.
Exclusion criteria
* Premature discontinuation of core study 28063. * Subjects who meet criteria listed below will receive IMP in study 28851: * Subjects who are eligible for participation in extension study 28851 but do not meet these criteria will not be treated with IMP but will undergo scheduled visits, irrespective of their treatment. * All subjects must satisfy the following criteria before Extension Study Day 1 (D1-EXT; defined as the first day of dosing in the extension study) to be eligible for treatment with IMP: * Eligibility for participation in extension study 28851. * For women of childbearing potential, a negative urine pregnancy test at eligibility assessment. * Female subjects of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for four (4) weeks before the first dose administered within the extension study, during the study and for twelve (12) weeks after the last dose of trial medication. Adequate contraception is defined as two barrier methods, or one barrier method with spermicide, or an intrauterine device, or use of a combined oral female hormonal contraceptive (or the definitions requested by health authorities and locally amended in the core study 28063). For the purposes of this trial, women of childbearing potential are defined as: All female subjects after puberty unless they are post-menopausal for at least two years or are surgically sterile (For Germany Only: Female subjects of childbearing potential must be willing to avoid pregnancy by using highly effective methods of contraception for approximately four (4) weeks prior to D1-EXT, during and for twelve (12) weeks after the last dose of trial medication. This requirement does not apply to surgically sterile subjects or to subjects who are postmenopausal for at least 2 years. Highly effective contraception is defined as any method or combination of methods which result in a low failure rate (i.e. less than (\<) 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, sexual abstinence, vasectomized partner, 2 barrier methods, or 1 barrier method with spermicide) * Willingness and ability to comply with study procedures for the duration of the study. * To be eligible for treatment with investigational medicinal product (IMP) in study 28851, the subjects must not meet any of the following criteria: * Non-eligibility for participation in extension study 28851 (premature discontinuation of core study 28063). * Major protocol violation or non-compliance in the core study. * Use of prohibited immunomodulatory / immunosuppressive therapies * Serum immunoglobulin G (IgG) level \<3 gram per liter (g/L) if the subject received atacicept in the core study, or serum IgG level \<6 g/L if the subject received placebo in the core study (to protect the blinding of the core study, the IgG level will be communicated to the treating physician only if it is too low for extension study participation and only after all Week 36 assessments performed within the core study have been completed). * Any condition, including laboratory findings that, in the opinion of the Investigator, constitutes a risk or a contraindication for participation in the extension study, or that could interfere with the study objectives, conduct or evaluation. * Known active clinically significant acute or chronic infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives. * Investigator judgement that treatment of the subject with atacicept in the extension study is not appropriate. * Aspartate aminotransferase (AST), or alanine aminotransferase (ALT), or alkaline phosphatase (AP) level greater than (\>)2.5 x upper limit of normal (ULN), or total bilirubin \>1.5 x ULN at eligibility assessment. * Clinically significant abnormality in any hematological test (e.g. hemoglobin \<100 g/L (6.21 millimoles per liter \[mmol/L\]), white blood cells \<3 x 10\^9 per liter (/L), platelets \<100 x 10\^9/L) at eligibility assessment. * Clinically significant abnormality on electrocardiogram (ECG) performed at eligibility assessment. * Presence of uncontrolled or New York Health Association (NYHA) class 3 or 4 congestive heart failure at Week 36 of the core study. * Moderate to severe renal impairment (creatinine clearance \<50 milliliter per minute (mL/min) according to Cockcroft-Gault equation). * Allergy or hypersensitivity to gadolinium (Gd). * Allergy or hypersensitivity to atacicept or to any of the components of the formulated atacicept. * Diagnosis or family history of Creutzfeldt-Jakob disease (CJD).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | From the first dose of study drug administration up to Week 24 | TEAEs were defined as AEs with a start date after or on the date of the first DB treatment injection in ATAMS Extension and that occurred anytime after treatment discontinuation, or up to the day before first Rebif® rescue medication injection in ATAMS Extension. A serious TEAE was an AE that resulted in any of the following: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE severity was graded as per Qualitative Toxicity Scale. Local injection site reactions (injection site: pain, redness, itching and swelling) throughout ATAMS Extension, starting after the first trial medication administration. If the subject experienced 1 or more of the above injection site symptoms, these were reported with the AE verbatim term injection site reaction. For all randomized subjects, there was an option of rescue treatment with Rebif® for 1 year beginning with the first injection of Rebif®). |
| Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36 | Blood pressure (systolic and diastolic) was measured after at least 3 minutes resting, with the subject in the seated position. |
| Change From Baseline in Vital Signs: Pulse Rate | Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36 | — |
| Change From Baseline in Vital Signs: Temperature | Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36 | — |
| Change From Baseline in Electrocardiogram (ECGs) | Baseline, Week 12 and 36 | — |
| Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels | Baseline up to Week 36 | Number of subjects with shifts from normal Grade (Grade 0) at Baseline to worse value at post-baseline (Grade 1 to Grade 4) according to the following criteria: IgA Grade 0: greater than or equal to (\>=) lower limit normal (LLN) 0.7 gram per liter (g/L); Grade 1: less than (\<) LLN - 0.5 g/L, Grade 2: \<0.5g/L -0.3 g/L, Grade 3: \<0.3 g/L -0.1 g/L, Grade 4: \< 0.1 g/L; IgG Grade 0: \>= LLN (7 g/L), Grade 1: \< LLN - 5 g/L, Grade 2: \<5g/L -4 g/L, Grade 3: \<4 g/L -3 g/L and Grade 4: \< 3 g/L; IgM Grade 0: \>= LLN (0.4 g/L), Grade 1: \< LLN - 0.3 g/L, Grade 2: \<0.3 g/L -0.2 g/L, Grade 3: \<0.2 g/L -0.1 g/L, and Grade 4: \< 0.1 g/L are presented in this outcome measure. |
| Number of Subjects With Positive Neutralizing Antibody (NAb) | Baseline, Week 12 and 36 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Clinical Attacks/Relapses | Baseline up to Week 24 | A clinical attack/relapse was defined as the fulfillment of all the following criteria: 1. Neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both i) neurological abnormality separated by at least 30 days from onset of a preceding clinical event, and ii) neurological abnormality lasting for at least 24 hours. 2. Absence of fever or known infection (fever with temperature (axillary, orally, or intra-auriculary) \> 37.5°C/99.5 °Fahrenheit). 3. Objective neurological impairment, correlating with the subject's reported symptoms, defined as either i) increase in at least 1 of the functional systems of the Expanded Disability Status Scale (EDSS), or ii) increase of the total EDSS score. EDSS overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. |
| Pharmacogenetics/Pharmacogenomics Analysis | Day 1 and Week 36 | Gene expression profiling and gene polymorphism identification were to be used to identify putative markers for response to treatment. * Genome-wide gene polymorphism characterization by genome-wide scan. * Targeted gene polymorphism identification of B-Lymphocyte Stimulator (BLyS) , APRIL, (receptor for B cell activating factor of the tumor necrosis factor \[TNF\] family) BAFF-R, (Transmembrane Activator) TACI and (B Cell Maturation Antigen) BCMA and HLA-DRB1 by direct genotyping or sequencing . |
| Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 12 | Baseline, Week 12 | EDSS is an ordinal scale in half-point increments that qualifies disability in participants with multiple sclerosis (MS). It assesses the 8 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder, cerebral and other) as well as ambulation. EDSS overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. |
| Change in Multiple Sclerosis Functional Composite (MSFC) Score at Week 12 | Week 12 | The MSFC is a multidimensional clinical outcome measure which consists of three sub-tests; Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Test-3(PASAT-3). The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The 9-Hole Peg Test is a quantitative measure of upper extremity (arm and hand) function. The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Standardized results (Z-scores) of these sub-tests and the overall MSFC Z-score as an average of these three Z-scores was calculated. Higher Z-scores reflect better neurological function and a positive change from baseline indicates improvement. An increase in score indicates an improvement (range -3 to +3). |
| Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject | Baseline, Week 12 and 24 | — |
| Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject | Baseline, Week 12 and Week 24 | — |
| Concentrations of Free and Total Atacicept | Baseline and Week 12 | — |
| Free B-Lymphocyte Stimulator (BLyS) and Free A Proliferation-Inducing Ligand (APRIL) Serum Concentrations. | Baseline, Week 12 and 36 | Levels of free APRIL and free BLyS: Free APRIL serum samples were to be analyzed by using a validated enzyme-linked immunosorbent assay (ELISA) with limits of detection of 0.3125 nanogram per milliliter (ng/mL) for free APRIL and free BlyS serum samples were analysed using a validated ELISA with limits of detection of 1.56 ng/mL. |
Countries
Australia, Belgium, Canada, Czechia, France, Germany, Lebanon, Lithuania, Netherlands, New Caledonia, Russia, Spain, Sweden, Switzerland, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
First/last participant (informed consent): 03 March 2009/13 August 2009. Last participant completed: 09 September 2009.
Pre-assignment details
A total of 324 subjects were screened and 255 were enrolled in ATAMS (28063; NCT00642902). Overall, 75 subjects randomized and treated in ATAMS were eligible to enter ATAMS Extension. However, 74 subjects were included in ATAMS Extension and 1 subject could not enter due to the premature termination of the trial.
Participants by arm
| Arm | Count |
|---|---|
| Atacicept 25 mg (With Loading) Subjects who received atacicept 25 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study. | 16 |
| Atacicept 75 mg (With Loading) Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study. | 19 |
| Atacicept 150 mg (With Loading) Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study. | 17 |
| Atacicept 150 mg (Without Loading) Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study. | 22 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Other | 0 | 2 | 0 | 0 |
| Overall Study | Premature Termination | 16 | 15 | 14 | 21 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 |
| Overall Study | Randomised but not Treated | 0 | 2 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Atacicept 25 mg (With Loading) | Atacicept 75 mg (With Loading) | Atacicept 150 mg (With Loading) | Atacicept 150 mg (Without Loading) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 39.4 years STANDARD_DEVIATION 8.4 | 36.8 years STANDARD_DEVIATION 9.1 | 37.4 years STANDARD_DEVIATION 11.2 | 34.4 years STANDARD_DEVIATION 8.6 | 36.8 years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 8 Participants | 12 Participants | 8 Participants | 16 Participants | 44 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 9 Participants | 6 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 16 | 9 / 17 | 8 / 15 | 12 / 22 |
| serious Total, serious adverse events | 0 / 16 | 1 / 17 | 0 / 15 | 0 / 22 |
Outcome results
Primary
Change From Baseline in Electrocardiogram (ECGs)
Time frame: Baseline, Week 12 and 36
Population: No summary tables were prepared for ECG parameters, and ECG data were not formally analyzed. However, a qualitative assessment of ECG morphology and rhythm was made by the Investigator and recorded in the electronic case report form (eCRF). ECG abnormalities considered significant by the investigator were reported as AEs.
Primary
Change From Baseline in Vital Signs: Pulse Rate
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
Population: Double-blind safety analysis set included all the subjects who received at least 1 dose of trial medication in the ATAMS extension study. Here 'n' signifies those subjects who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 2 (n=15, 13, 14, 21) | -2.1 beats per minute (beats/min) | Standard Deviation 5.1 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 4 (n=15, 14, 12, 21) | 0.6 beats per minute (beats/min) | Standard Deviation 8.7 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 8 (n=13, 11, 12, 16) | -1.7 beats per minute (beats/min) | Standard Deviation 9.2 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 12 (n=11, 12, 8, 16) | -0.5 beats per minute (beats/min) | Standard Deviation 6.2 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 16 (n=7, 9, 6, 12) | 3.9 beats per minute (beats/min) | Standard Deviation 4.7 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 20 (n=3, 7, 2, 6) | -0.3 beats per minute (beats/min) | Standard Deviation 2.1 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 24 (n=2, 4, 1, 6) | 2.5 beats per minute (beats/min) | Standard Deviation 0.7 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 36 (n=0, 1, 0, 0) | NA beats per minute (beats/min) | — |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 20 (n=3, 7, 2, 6) | 3.9 beats per minute (beats/min) | Standard Deviation 8.3 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 16 (n=7, 9, 6, 12) | 1.1 beats per minute (beats/min) | Standard Deviation 10.5 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 4 (n=15, 14, 12, 21) | -0.6 beats per minute (beats/min) | Standard Deviation 9.2 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 36 (n=0, 1, 0, 0) | 7.0 beats per minute (beats/min) | — |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 24 (n=2, 4, 1, 6) | -5.3 beats per minute (beats/min) | Standard Deviation 9.4 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 12 (n=11, 12, 8, 16) | 0.7 beats per minute (beats/min) | Standard Deviation 9.5 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 8 (n=13, 11, 12, 16) | -3.4 beats per minute (beats/min) | Standard Deviation 9.1 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 2 (n=15, 13, 14, 21) | -3.5 beats per minute (beats/min) | Standard Deviation 5.5 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 24 (n=2, 4, 1, 6) | -22.0 beats per minute (beats/min) | — |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 8 (n=13, 11, 12, 16) | 1.3 beats per minute (beats/min) | Standard Deviation 8.7 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 12 (n=11, 12, 8, 16) | -1.5 beats per minute (beats/min) | Standard Deviation 8.9 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 16 (n=7, 9, 6, 12) | -0.2 beats per minute (beats/min) | Standard Deviation 4.8 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 20 (n=3, 7, 2, 6) | -5.0 beats per minute (beats/min) | Standard Deviation 9.9 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 36 (n=0, 1, 0, 0) | NA beats per minute (beats/min) | — |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 2 (n=15, 13, 14, 21) | -3.8 beats per minute (beats/min) | Standard Deviation 10.4 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 4 (n=15, 14, 12, 21) | 0.7 beats per minute (beats/min) | Standard Deviation 8.2 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 8 (n=13, 11, 12, 16) | 4.4 beats per minute (beats/min) | Standard Deviation 12.4 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 12 (n=11, 12, 8, 16) | 4.5 beats per minute (beats/min) | Standard Deviation 9.5 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 4 (n=15, 14, 12, 21) | 2.0 beats per minute (beats/min) | Standard Deviation 8 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 2 (n=15, 13, 14, 21) | 3.6 beats per minute (beats/min) | Standard Deviation 11.4 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 16 (n=7, 9, 6, 12) | 3.8 beats per minute (beats/min) | Standard Deviation 9.1 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 36 (n=0, 1, 0, 0) | NA beats per minute (beats/min) | — |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 24 (n=2, 4, 1, 6) | 9.0 beats per minute (beats/min) | Standard Deviation 5.3 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Pulse Rate | Week 20 (n=3, 7, 2, 6) | 11.0 beats per minute (beats/min) | Standard Deviation 8.8 |
Primary
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Blood pressure (systolic and diastolic) was measured after at least 3 minutes resting, with the subject in the seated position.
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
Population: Double-blind safety analysis set included all the subjects who received at least 1 dose of trial medication in the ATAMS extension study. Here 'n' signifies those subjects who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 12 (n=11, 12, 8, 16) | -3.8 millimeter of mercury (mmHg) | Standard Deviation 11.1 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 2 (n=15, 13, 14, 21) | -2.1 millimeter of mercury (mmHg) | Standard Deviation 8.2 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 4 (n=15, 14, 12, 21) | -0.5 millimeter of mercury (mmHg) | Standard Deviation 9 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 8 (n=13, 11, 12, 16) | -2.8 millimeter of mercury (mmHg) | Standard Deviation 7.7 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 36 (n=0, 1, 0, 0) | NA millimeter of mercury (mmHg) | — |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 16 (n=7, 9, 6, 12) | -1.6 millimeter of mercury (mmHg) | Standard Deviation 14.2 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 20 (n=3, 7, 2, 6) | -2.0 millimeter of mercury (mmHg) | Standard Deviation 17.1 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 24 (n=2, 4, 1, 6) | 0.0 millimeter of mercury (mmHg) | Standard Deviation 0 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 36 (n=0, 1, 0, 0) | NA millimeter of mercury (mmHg) | — |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 2 (n = 13, 16, 14, 20) | 2.6 millimeter of mercury (mmHg) | Standard Deviation 8.3 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 4 (n = 15, 14, 12, 21) | 2.1 millimeter of mercury (mmHg) | Standard Deviation 7.9 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 8 (n = 13, 11, 12, 16) | 0.8 millimeter of mercury (mmHg) | Standard Deviation 10.5 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 12 (n = 11, 12, 8, 16) | 3.0 millimeter of mercury (mmHg) | Standard Deviation 11.7 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 16 (n=7, 9, 6, 12) | 5.9 millimeter of mercury (mmHg) | Standard Deviation 13.4 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 20 (n=3, 7, 2, 6) | 2.0 millimeter of mercury (mmHg) | Standard Deviation 23.1 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 24 (n=2, 4, 1, 6) | 5.0 millimeter of mercury (mmHg) | Standard Deviation 7.1 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 24 (n=2, 4, 1, 6) | -5.0 millimeter of mercury (mmHg) | Standard Deviation 4.1 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 36 (n=0, 1, 0, 0) | -18.0 millimeter of mercury (mmHg) | — |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 24 (n=2, 4, 1, 6) | -6.3 millimeter of mercury (mmHg) | Standard Deviation 2.5 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 2 (n=15, 13, 14, 21) | -1.9 millimeter of mercury (mmHg) | Standard Deviation 8.4 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 4 (n=15, 14, 12, 21) | -0.4 millimeter of mercury (mmHg) | Standard Deviation 8.7 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 20 (n=3, 7, 2, 6) | -9.7 millimeter of mercury (mmHg) | Standard Deviation 14.8 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 8 (n=13, 11, 12, 16) | -1.6 millimeter of mercury (mmHg) | Standard Deviation 8.7 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 16 (n=7, 9, 6, 12) | -9.0 millimeter of mercury (mmHg) | Standard Deviation 18.6 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 36 (n=0, 1, 0, 0) | -8.0 millimeter of mercury (mmHg) | — |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 2 (n = 13, 16, 14, 20) | -3.0 millimeter of mercury (mmHg) | Standard Deviation 9.5 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 12 (n=11, 12, 8, 16) | -4.8 millimeter of mercury (mmHg) | Standard Deviation 8.1 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 4 (n = 15, 14, 12, 21) | -2.4 millimeter of mercury (mmHg) | Standard Deviation 13.7 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 20 (n=3, 7, 2, 6) | -4.4 millimeter of mercury (mmHg) | Standard Deviation 6 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 8 (n = 13, 11, 12, 16) | -2.1 millimeter of mercury (mmHg) | Standard Deviation 12 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 16 (n=7, 9, 6, 12) | -2.9 millimeter of mercury (mmHg) | Standard Deviation 9 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 12 (n = 11, 12, 8, 16) | -5.8 millimeter of mercury (mmHg) | Standard Deviation 15.3 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 8 (n = 13, 11, 12, 16) | -1.1 millimeter of mercury (mmHg) | Standard Deviation 12.5 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 36 (n=0, 1, 0, 0) | NA millimeter of mercury (mmHg) | — |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 36 (n=0, 1, 0, 0) | NA millimeter of mercury (mmHg) | — |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 12 (n=11, 12, 8, 16) | -3.5 millimeter of mercury (mmHg) | Standard Deviation 9.9 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 12 (n = 11, 12, 8, 16) | -3.4 millimeter of mercury (mmHg) | Standard Deviation 10.2 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 20 (n=3, 7, 2, 6) | -0.5 millimeter of mercury (mmHg) | Standard Deviation 0.7 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 2 (n=15, 13, 14, 21) | -3.6 millimeter of mercury (mmHg) | Standard Deviation 10.6 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 24 (n=2, 4, 1, 6) | 0.0 millimeter of mercury (mmHg) | — |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 16 (n=7, 9, 6, 12) | -2.3 millimeter of mercury (mmHg) | Standard Deviation 4.2 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 4 (n = 15, 14, 12, 21) | -5.1 millimeter of mercury (mmHg) | Standard Deviation 12.6 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 4 (n=15, 14, 12, 21) | -5.1 millimeter of mercury (mmHg) | Standard Deviation 9.2 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 2 (n = 13, 16, 14, 20) | -1.2 millimeter of mercury (mmHg) | Standard Deviation 10.7 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 24 (n=2, 4, 1, 6) | 10.0 millimeter of mercury (mmHg) | — |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 16 (n=7, 9, 6, 12) | -2.0 millimeter of mercury (mmHg) | Standard Deviation 12.2 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 8 (n=13, 11, 12, 16) | -5.9 millimeter of mercury (mmHg) | Standard Deviation 10.2 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 20 (n=3, 7, 2, 6) | 2.0 millimeter of mercury (mmHg) | Standard Deviation 4.2 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 8 (n=13, 11, 12, 16) | 0.1 millimeter of mercury (mmHg) | Standard Deviation 11 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 12 (n=11, 12, 8, 16) | -2.4 millimeter of mercury (mmHg) | Standard Deviation 10.3 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 16 (n=7, 9, 6, 12) | -1.6 millimeter of mercury (mmHg) | Standard Deviation 7.7 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 16 (n=7, 9, 6, 12) | -2.3 millimeter of mercury (mmHg) | Standard Deviation 10 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 20 (n=3, 7, 2, 6) | 3.7 millimeter of mercury (mmHg) | Standard Deviation 6.3 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 24 (n=2, 4, 1, 6) | -5.3 millimeter of mercury (mmHg) | Standard Deviation 7.7 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 24 (n=2, 4, 1, 6) | -1.0 millimeter of mercury (mmHg) | Standard Deviation 9.8 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 36 (n=0, 1, 0, 0) | NA millimeter of mercury (mmHg) | — |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 2 (n = 13, 16, 14, 20) | -0.2 millimeter of mercury (mmHg) | Standard Deviation 9.8 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 20 (n=3, 7, 2, 6) | 3.3 millimeter of mercury (mmHg) | Standard Deviation 6 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 4 (n = 15, 14, 12, 21) | -0.1 millimeter of mercury (mmHg) | Standard Deviation 9.9 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 8 (n = 13, 11, 12, 16) | 0.4 millimeter of mercury (mmHg) | Standard Deviation 11 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 36 (n=0, 1, 0, 0) | NA millimeter of mercury (mmHg) | — |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 2 (n=15, 13, 14, 21) | 0.3 millimeter of mercury (mmHg) | Standard Deviation 8.6 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Week 12 (n = 11, 12, 8, 16) | -0.9 millimeter of mercury (mmHg) | Standard Deviation 11.3 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Week 4 (n=15, 14, 12, 21) | 0.1 millimeter of mercury (mmHg) | Standard Deviation 7.7 |
Primary
Change From Baseline in Vital Signs: Temperature
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
Population: Double-blind safety analysis set included all the subjects who received at least 1 dose of trial medication in the ATAMS extension study. Here 'n' signifies those subjects who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 2 (n=15, 13, 14, 21) | -0.09 Degree Celsius | Standard Deviation 0.27 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 16 (n=7, 9, 6, 12) | -0.10 Degree Celsius | Standard Deviation 0.21 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 36 (n=0, 1, 0, 0) | NA Degree Celsius | — |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 4 (n=15, 14, 12, 21) | -0.03 Degree Celsius | Standard Deviation 0.24 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 20 (n=3, 7, 2, 6) | -0.37 Degree Celsius | Standard Deviation 0.35 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 8 (n=13, 11, 12, 16) | -0.03 Degree Celsius | Standard Deviation 0.4 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 12 (n=11, 12, 8, 16) | 0.02 Degree Celsius | Standard Deviation 0.19 |
| Atacicept 25 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 24 (n=2, 4, 1, 6) | 0.05 Degree Celsius | Standard Deviation 0.07 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 12 (n=11, 12, 8, 16) | 0.08 Degree Celsius | Standard Deviation 0.36 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 8 (n=13, 11, 12, 16) | 0.05 Degree Celsius | Standard Deviation 0.1 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 20 (n=3, 7, 2, 6) | 0.16 Degree Celsius | Standard Deviation 0.56 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 36 (n=0, 1, 0, 0) | 0.70 Degree Celsius | — |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 16 (n=7, 9, 6, 12) | 0.17 Degree Celsius | Standard Deviation 0.35 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 4 (n=15, 14, 12, 21) | 0.05 Degree Celsius | Standard Deviation 0.42 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 2 (n=15, 13, 14, 21) | 0.09 Degree Celsius | Standard Deviation 0.27 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 24 (n=2, 4, 1, 6) | 0.30 Degree Celsius | Standard Deviation 0.59 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 24 (n=2, 4, 1, 6) | 0.00 Degree Celsius | — |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 2 (n=15, 13, 14, 21) | 0.03 Degree Celsius | Standard Deviation 0.21 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 4 (n=15, 14, 12, 21) | 0.03 Degree Celsius | Standard Deviation 0.24 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 8 (n=13, 11, 12, 16) | 0.03 Degree Celsius | Standard Deviation 0.28 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 36 (n=0, 1, 0, 0) | NA Degree Celsius | — |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 12 (n=11, 12, 8, 16) | 0.09 Degree Celsius | Standard Deviation 0.57 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 16 (n=7, 9, 6, 12) | -0.05 Degree Celsius | Standard Deviation 0.23 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Vital Signs: Temperature | Week 20 (n=3, 7, 2, 6) | -0.25 Degree Celsius | Standard Deviation 0.07 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Temperature | Week 24 (n=2, 4, 1, 6) | -0.07 Degree Celsius | Standard Deviation 0.26 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Temperature | Week 8 (n=13, 11, 12, 16) | -0.14 Degree Celsius | Standard Deviation 0.25 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Temperature | Week 20 (n=3, 7, 2, 6) | -0.08 Degree Celsius | Standard Deviation 0.45 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Temperature | Week 16 (n=7, 9, 6, 12) | 0.01 Degree Celsius | Standard Deviation 0.42 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Temperature | Week 4 (n=15, 14, 12, 21) | -0.12 Degree Celsius | Standard Deviation 0.31 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Temperature | Week 36 (n=0, 1, 0, 0) | NA Degree Celsius | — |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Temperature | Week 2 (n=15, 13, 14, 21) | -0.07 Degree Celsius | Standard Deviation 0.36 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Vital Signs: Temperature | Week 12 (n=11, 12, 8, 16) | -0.15 Degree Celsius | Standard Deviation 0.34 |
Primary
Number of Subjects With Positive Neutralizing Antibody (NAb)
Time frame: Baseline, Week 12 and 36
Population: Appropriate method/test was not established to identify the positive neutralizing antibodies for atacicept. Hence, this outcome measure was not assessed.
Primary
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity
TEAEs were defined as AEs with a start date after or on the date of the first DB treatment injection in ATAMS Extension and that occurred anytime after treatment discontinuation, or up to the day before first Rebif® rescue medication injection in ATAMS Extension. A serious TEAE was an AE that resulted in any of the following: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE severity was graded as per Qualitative Toxicity Scale. Local injection site reactions (injection site: pain, redness, itching and swelling) throughout ATAMS Extension, starting after the first trial medication administration. If the subject experienced 1 or more of the above injection site symptoms, these were reported with the AE verbatim term injection site reaction. For all randomized subjects, there was an option of rescue treatment with Rebif® for 1 year beginning with the first injection of Rebif®).
Time frame: From the first dose of study drug administration up to Week 24
Population: Double-blind safety analysis set included all the subjects who received at least 1 dose of trial medication in the ATAMS extension study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild malignancies | 0 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe injection site reaction | 0 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe TEAEs | 0 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild infections | 1 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe infections | 0 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate infections | 0 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild serious TEAEs | 0 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild TEAEs | 5 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe malignancies | 0 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate serious TEAEs | 0 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate TEAEs | 2 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe serious TEAEs | 0 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate malignancies | 1 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild injection site reaction | 2 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate injection site reaction | 0 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate injection site reaction | 0 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild injection site reaction | 2 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe injection site reaction | 0 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild TEAEs | 8 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe infections | 0 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate malignancies | 0 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe TEAEs | 0 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild malignancies | 0 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe serious TEAEs | 0 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate infections | 1 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild infections | 2 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe malignancies | 0 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate TEAEs | 4 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild serious TEAEs | 0 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate serious TEAEs | 1 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild serious TEAEs | 0 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild TEAEs | 8 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate TEAEs | 6 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe TEAEs | 0 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate serious TEAEs | 0 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe serious TEAEs | 0 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild injection site reaction | 5 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate injection site reaction | 0 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe injection site reaction | 0 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild infections | 4 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate infections | 2 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe infections | 0 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild malignancies | 0 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate malignancies | 0 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe malignancies | 0 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe infections | 0 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate injection site reaction | 2 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild injection site reaction | 5 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe malignancies | 0 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild malignancies | 0 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe serious TEAEs | 0 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate serious TEAEs | 0 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate TEAEs | 4 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate malignancies | 0 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild serious TEAEs | 0 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe TEAEs | 1 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Moderate infections | 0 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild infections | 6 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Severe injection site reaction | 0 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity | Mild TEAEs | 13 Subjects |
Primary
Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels
Number of subjects with shifts from normal Grade (Grade 0) at Baseline to worse value at post-baseline (Grade 1 to Grade 4) according to the following criteria: IgA Grade 0: greater than or equal to (\>=) lower limit normal (LLN) 0.7 gram per liter (g/L); Grade 1: less than (\<) LLN - 0.5 g/L, Grade 2: \<0.5g/L -0.3 g/L, Grade 3: \<0.3 g/L -0.1 g/L, Grade 4: \< 0.1 g/L; IgG Grade 0: \>= LLN (7 g/L), Grade 1: \< LLN - 5 g/L, Grade 2: \<5g/L -4 g/L, Grade 3: \<4 g/L -3 g/L and Grade 4: \< 3 g/L; IgM Grade 0: \>= LLN (0.4 g/L), Grade 1: \< LLN - 0.3 g/L, Grade 2: \<0.3 g/L -0.2 g/L, Grade 3: \<0.2 g/L -0.1 g/L, and Grade 4: \< 0.1 g/L are presented in this outcome measure.
Time frame: Baseline up to Week 36
Population: Intent-to-treat (ITT) population included all randomized subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atacicept 25 mg (With Loading) | Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels | IgA | 1 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels | IgM | 7 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels | IgG | 4 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels | IgA | 3 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels | IgM | 6 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels | IgG | 8 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels | IgG | 12 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels | IgA | 10 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels | IgM | 14 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels | IgA | 9 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels | IgM | 7 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels | IgG | 5 Subjects |
Secondary
Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 12
EDSS is an ordinal scale in half-point increments that qualifies disability in participants with multiple sclerosis (MS). It assesses the 8 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder, cerebral and other) as well as ambulation. EDSS overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.
Time frame: Baseline, Week 12
Population: Intent-to-treat (ITT) population included all randomized subjects. N signifies (total number of subjects analyzed) the number of evaluable subjects for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atacicept 25 mg (With Loading) | Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 12 | 0.09 Units on a scale | Standard Deviation 0.58 |
| Atacicept 75 mg (With Loading) | Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 12 | 0.04 Units on a scale | Standard Deviation 0.97 |
| Atacicept 150 mg (With Loading) | Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 12 | 0.50 Units on a scale | Standard Deviation 0.85 |
| Atacicept 150 mg (Without Loading) | Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 12 | -0.06 Units on a scale | Standard Deviation 0.75 |
Secondary
Change in Multiple Sclerosis Functional Composite (MSFC) Score at Week 12
The MSFC is a multidimensional clinical outcome measure which consists of three sub-tests; Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Test-3(PASAT-3). The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The 9-Hole Peg Test is a quantitative measure of upper extremity (arm and hand) function. The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Standardized results (Z-scores) of these sub-tests and the overall MSFC Z-score as an average of these three Z-scores was calculated. Higher Z-scores reflect better neurological function and a positive change from baseline indicates improvement. An increase in score indicates an improvement (range -3 to +3).
Time frame: Week 12
Population: Intent-to-treat (ITT) population included all randomized subjects. N signifies number of evaluable subjects for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atacicept 25 mg (With Loading) | Change in Multiple Sclerosis Functional Composite (MSFC) Score at Week 12 | 0.21 z-score | Standard Deviation 0.4 |
| Atacicept 75 mg (With Loading) | Change in Multiple Sclerosis Functional Composite (MSFC) Score at Week 12 | 0.04 z-score | Standard Deviation 0.47 |
| Atacicept 150 mg (With Loading) | Change in Multiple Sclerosis Functional Composite (MSFC) Score at Week 12 | -0.01 z-score | Standard Deviation 0.24 |
| Atacicept 150 mg (Without Loading) | Change in Multiple Sclerosis Functional Composite (MSFC) Score at Week 12 | 0.07 z-score | Standard Deviation 0.34 |
Secondary
Concentrations of Free and Total Atacicept
Time frame: Baseline and Week 12
Population: This outcome measure was not assessed due to lack of a valid assay during the usable time period of the samples.
Secondary
Free B-Lymphocyte Stimulator (BLyS) and Free A Proliferation-Inducing Ligand (APRIL) Serum Concentrations.
Levels of free APRIL and free BLyS: Free APRIL serum samples were to be analyzed by using a validated enzyme-linked immunosorbent assay (ELISA) with limits of detection of 0.3125 nanogram per milliliter (ng/mL) for free APRIL and free BlyS serum samples were analysed using a validated ELISA with limits of detection of 1.56 ng/mL.
Time frame: Baseline, Week 12 and 36
Population: This outcome measure was not assessed due to lack of a valid assay for measuring BLyS and APRIL.
Secondary
Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject
Time frame: Baseline, Week 12 and 24
Population: Intent-to-treat (ITT) population included all randomized subjects. n signifies the number of evaluable subjects for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atacicept 25 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject | Baseline (n=16, 19, 17, 22) | 1.1 Number of lesions per subject | Standard Deviation 2.2 |
| Atacicept 25 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject | Week 24 (n=2, 3, 1, 6) | 0.00 Number of lesions per subject | Standard Deviation 0 |
| Atacicept 25 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject | Week 12 (n=11, 11, 7, 15) | 0.27 Number of lesions per subject | Standard Deviation 0.47 |
| Atacicept 75 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject | Baseline (n=16, 19, 17, 22) | 2.3 Number of lesions per subject | Standard Deviation 5 |
| Atacicept 75 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject | Week 24 (n=2, 3, 1, 6) | 2.00 Number of lesions per subject | Standard Deviation 2 |
| Atacicept 75 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject | Week 12 (n=11, 11, 7, 15) | 0.64 Number of lesions per subject | Standard Deviation 1.29 |
| Atacicept 150 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject | Week 12 (n=11, 11, 7, 15) | 1.00 Number of lesions per subject | Standard Deviation 1.15 |
| Atacicept 150 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject | Baseline (n=16, 19, 17, 22) | 0.8 Number of lesions per subject | Standard Deviation 1.4 |
| Atacicept 150 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject | Week 24 (n=2, 3, 1, 6) | 0.00 Number of lesions per subject | Standard Deviation 0 |
| Atacicept 150 mg (Without Loading) | Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject | Baseline (n=16, 19, 17, 22) | 0.9 Number of lesions per subject | Standard Deviation 1.4 |
| Atacicept 150 mg (Without Loading) | Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject | Week 24 (n=2, 3, 1, 6) | 0.83 Number of lesions per subject | Standard Deviation 0.75 |
| Atacicept 150 mg (Without Loading) | Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject | Week 12 (n=11, 11, 7, 15) | 2.27 Number of lesions per subject | Standard Deviation 7.16 |
Secondary
Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject
Time frame: Baseline, Week 12 and Week 24
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atacicept 25 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject | Baseline (n=16, 19, 17, 22) | 4792.76 Cubic millimeter | Standard Deviation 3152.56 |
| Atacicept 25 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject | Week 24 (n=2, 3, 1, 6) | 1699.60 Cubic millimeter | Standard Deviation 586.76 |
| Atacicept 25 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject | Week 12 (n=11, 11, 7, 15) | 5604.42 Cubic millimeter | Standard Deviation 5154.52 |
| Atacicept 75 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject | Baseline (n=16, 19, 17, 22) | 8196.59 Cubic millimeter | Standard Deviation 8888.74 |
| Atacicept 75 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject | Week 24 (n=2, 3, 1, 6) | 6814.60 Cubic millimeter | Standard Deviation 6643 |
| Atacicept 75 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject | Week 12 (n=11, 11, 7, 15) | 7634.89 Cubic millimeter | Standard Deviation 6340.19 |
| Atacicept 150 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject | Week 12 (n=11, 11, 7, 15) | 4934.03 Cubic millimeter | Standard Deviation 4802.98 |
| Atacicept 150 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject | Baseline (n=16, 19, 17, 22) | 6158.04 Cubic millimeter | Standard Deviation 7945.59 |
| Atacicept 150 mg (With Loading) | Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject | Week 24 (n=2, 3, 1, 6) | 1931.40 Cubic millimeter | Standard Deviation 0 |
| Atacicept 150 mg (Without Loading) | Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject | Baseline (n=16, 19, 17, 22) | 5868.84 Cubic millimeter | Standard Deviation 7170.81 |
| Atacicept 150 mg (Without Loading) | Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject | Week 24 (n=2, 3, 1, 6) | 5541.80 Cubic millimeter | Standard Deviation 5614.73 |
| Atacicept 150 mg (Without Loading) | Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject | Week 12 (n=11, 11, 7, 15) | 5365.63 Cubic millimeter | Standard Deviation 7445.87 |
Secondary
Number of Subjects With Clinical Attacks/Relapses
A clinical attack/relapse was defined as the fulfillment of all the following criteria: 1. Neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both i) neurological abnormality separated by at least 30 days from onset of a preceding clinical event, and ii) neurological abnormality lasting for at least 24 hours. 2. Absence of fever or known infection (fever with temperature (axillary, orally, or intra-auriculary) \> 37.5°C/99.5 °Fahrenheit). 3. Objective neurological impairment, correlating with the subject's reported symptoms, defined as either i) increase in at least 1 of the functional systems of the Expanded Disability Status Scale (EDSS), or ii) increase of the total EDSS score. EDSS overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.
Time frame: Baseline up to Week 24
Population: Intent-to-treat (ITT) population included all randomized subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atacicept 25 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | 1 Relapse | 0 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | 3 Relapse | 0 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | Greater than or equal to (>=) 4 Relapse | 0 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | 2 Relapse | 0 Subjects |
| Atacicept 25 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | No Relapse | 16 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | No Relapse | 16 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | Greater than or equal to (>=) 4 Relapse | 0 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | 1 Relapse | 3 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | 2 Relapse | 0 Subjects |
| Atacicept 75 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | 3 Relapse | 0 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | 2 Relapse | 0 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | Greater than or equal to (>=) 4 Relapse | 0 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | No Relapse | 15 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | 3 Relapse | 0 Subjects |
| Atacicept 150 mg (With Loading) | Number of Subjects With Clinical Attacks/Relapses | 1 Relapse | 2 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Clinical Attacks/Relapses | Greater than or equal to (>=) 4 Relapse | 0 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Clinical Attacks/Relapses | 2 Relapse | 0 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Clinical Attacks/Relapses | No Relapse | 21 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Clinical Attacks/Relapses | 1 Relapse | 1 Subjects |
| Atacicept 150 mg (Without Loading) | Number of Subjects With Clinical Attacks/Relapses | 3 Relapse | 0 Subjects |
Secondary
Pharmacogenetics/Pharmacogenomics Analysis
Gene expression profiling and gene polymorphism identification were to be used to identify putative markers for response to treatment. * Genome-wide gene polymorphism characterization by genome-wide scan. * Targeted gene polymorphism identification of B-Lymphocyte Stimulator (BLyS) , APRIL, (receptor for B cell activating factor of the tumor necrosis factor \[TNF\] family) BAFF-R, (Transmembrane Activator) TACI and (B Cell Maturation Antigen) BCMA and HLA-DRB1 by direct genotyping or sequencing .
Time frame: Day 1 and Week 36
Population: Genetic/genomic analysis was not performed as the trial was terminated early.