Sickle Cell Disease (SCD)
Conditions
Keywords
SEG101, Sickle cell disease, SCD, crizanlizumab, pediatric, pharmacokinetic, P-selectin, Covid-19, Coronavirus disease 2019
Brief summary
The purpose of this study was to confirm and to establish appropriate dosing and to evaluate the safety in pediatric participants ages 2 to \<18 years with a history of Vaso-Occlusive Crisis (VOC) with or without Hydroxyurea/Hydroxycarbamide (HU/HC), receiving crizanlizumab for 2 years. The efficacy and safety of crizanlizumab was previously demonstrated in adults with sickle cell disease. The approach was to extrapolate from the pharmacokinetics (PK)/pharmacodynamics (PD) already established in the adult population. The study was designed as a Phase II, multicenter, open-label study.
Detailed description
This was an open-label, single-arm study of crizanlizumab in sickle-cell disease (SCD) pediatric participants. This study consisted of 2 parts, Part A and Part B. In Part A, the dose for 3 age groups (see groups below), was first confirmed on the basis of single and multiple dose (steady state) PK data and key safety data from an initial subgroup of participants. In Part B, safety and efficacy were collected from additional participants from 6 to \<18 years (Groups 1 and 2, only). At least 100 participants were planned to be enrolled in the trial in total, split in 3 age groups: * Group 1 (age 12 to \<18 years): at least 26 participants (≥8 in Part A and ≥18 in Part B), * Group 2 (age 6 to \<12 years): at least 26 participants (≥8 in Part A and ≥18 in Part B), * Group 3 (age 2 to \<6 years): at least 8 participants (≥8 Part A). Crizanlizumab was administered every 4 weeks with a loading dose 2 weeks after the first dosing (i.e., by i.v. infusion) on Week 1 Day 1, Week 3 Day 1, and then day 1 of every fourth week) for up to 2 years. The initial dose of crizanlizumab was 5 mg/kg dose for Group 1 and Group 2 Part A. It was later adjusted to 8.5 mg/kg for Group 2 and 3 based on final dose confirmation from emerging PK data analysis and safety considerations determined in Part A of the study.
Interventions
DRUGCrizanlizumab
Crizanlizumab (SEG101) is a concentrate for solution for infusion, i.v. use. Supplied in single use 10 mL vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients ages 2 to \<18 years 2. Confirmed diagnosis of SCD (any genotype including HbSS, HbSC, HbSβ0-thalassemia, HbSβ+-thalassemia patients, and others) by hemoglobin electrophoresis or/and high-performance liquid chromatography (HPLC) \[performed locally\]. Confirmation of diagnosis by two accepted methods is recommended. 3. Experienced at least 1 VOC within the preceding 12 months prior to screening, as determined by medical history. Prior VOC must have resolved at least 7 days prior to the first dose in the study and must include all the following: a.the occurrence of appropriate symptoms (see VOC definition in Section 7.2.1.1), b.either a visit to a medical facility or healthcare professional, c.receipt of oral/parenteral opioid or parenteral NSAIDs 4. If receiving HU/HC, L-glutamine or erythropoietin stimulating agent, must have been receiving the drug consistently for at least 6 months prior to screening and plan to continue taking it at the same dose and schedule during the trial. Patients who have not been receiving such drugs must have been off them for at least 6 months prior to screening. . Dose alterations of HU/HC, L-glutamine or erythropoietin stimulating agent during Part A are not allowed, and if this occurs, the participant will enter directly to Part B. 5. Received standard age-appropriate care for SCD, including penicillin prophylaxis, pneumococcal immunization, and parental education. 6. Performance status: Karnofsky ≥ 50% for patients \>10 years of age, and Lansky ≥ 50 for patients ≤ 10 years of age. 7. Patient must meet the following laboratory values prior to Week 1 Day 1: Absolute Neutrophil Count ≥1.0 x 109/L , Platelets ≥75 x 109/L, Hemoglobin (Hgb) \> 5.5 g/dL 8. Patient must have adequate renal and hepatic function as defined:Estimated Glomerular filtration rate (eGFR) ≥ 75 mL/min/1.73 m2 using Schwartz formula, Direct (conjugated) bilirubin ≤ 2.0 x ULN, Alanine transaminase (ALT) ≤ 3.0 x ULN, 9. Transcranial Doppler (TCD) for patients aged 2 to \< 16 years at time of screening, with HbSS, HbSβ0-thalassemia, and HbSD disease indicating low risk for stroke (per investigator). Please refer to Section 7.2.2.6 for details 10. Written informed consent/assent, according to local guidelines, signed by the patient and / or by the parents or legal guardian prior to any study related screening procedures are performed. 11. Female of non-childbearing potential or with negative serum pregnancy test on Screening and a negative urine pregnancy test (dipstick) prior to dosing on Day 1.
Exclusion criteria
1. History of stem cell transplant. 2. Received any blood products within 30 days prior to Week 1 Day 1 dosing. 3. Plan to participate in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) or undergo exchange transfusions/plasmapheresis during the study. Patients requiring episodic transfusion (simple or exchange) in response to worsened anemia or VOC are permitted. 4. Patients with bleeding disorders 6.Contraindication or hypersensitivity to any drug from similar class as study drug or to any excipients of the study drug formulation. 7.History of severe hypersensitivity reaction to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction 8.Received a monoclonal antibody or immunoglobulin-based therapy within 6 months of Screening, or has documented immunogenicity to a prior monoclonal antibody. 9.Received active treatment on another investigational trial within 30 days (or 5 half -lives of that agent, whichever is greater) prior to Screening or plans to participate in another investigational drug trial. 10.Pregnant females or females who have given birth within the past 90 days or who are breastfeeding. 11\. Any documented history of a clinical stroke or intracranial hemorrhage, or an uninvestigated neurologic finding within the past 12 months. Silent infarcts (only present on imaging) are not excluding patients from study participation 12.Any abnormal TCD within the past 12 months. 13.Use of therapeutic anticoagulation (prophylactic doses permitted) or antiplatelet therapy (other than aspirin) within the 10 days prior to Week 1 Day 1 dosing. 14.Hospitalized within 7 days prior to Week 1 Day 1 dosing. 15.Planning to undergo a major surgical procedure during the duration of the study. 16.Planning to initiate or terminate HU/HC or L-glutamine while on study (except if needed to terminate for safety reasons). 17.Patient with active human immunodeficiency virus (HIV) infection (detectable viral load). 18.Patients with known active Hepatitis B infection. 19.Patients with known Hepatitis C history. 20.Significant active infection or immune deficiency (including chronic use of immunosuppressive drugs) in the opinion of the investigator. 21.Malignant disease. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; any completely resected carcinoma in situ. 22.Has a serious mental or physical illness, which, in the opinion of the Investigator would compromise participation in the study. 23.Any condition which, in the opinion of the investigator, is likely to interfere with the successful collection of the measurements required for the study 24.Resting QTcF ≥450 msec at pretreatment (baseline) for patients under 12 years of age and ≥450 msec for males and ≥460 msec for female patients 12 years and older. 25.Cardiac or cardiac repolarization abnormality, including any of the following: a. History of myocardial infarction (MI), uncontrolled congestive heart failure, unstable angina, or coronary bypass graft (CABG) within 6 months prior to starting study treatment, b. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (bifascicular block, Mobitz Type II, and third degree AV block), c. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome ( Risk factors for Torsade de Pointes (TdP), including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/ symptomatic bradycardia, Inability to determine the QTcF). 26\. Sexually active females who are unwilling to comply with reliable method of birth control until 15 weeks following last dose of study drug. 28.Not able to understand and to comply with study instructions and requirements. 29.Patients who are an employee of the sponsor or investigator or otherwise dependent on them. 30.Patients who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities. 31.Patients who received prior crizanlizumab treatment and/or other selectin targeting agents are not allowed 32.Patients having taken voxelotor less than 30 days prior to Screening, or planning to take voxelotor while on study are not allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): AUCd15 of Crizanlizumab After First Dose - Part A | Day 1 to Day 15 | The area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) following the first dose. AUCd15 was calculated based on serum concentrations of crizanlizumab. |
| Pharmacokinetics (PK) - AUCtau for Serum Crizanlizumab After Multiple Doses - Part A - Steady State | Week 15 - Steady state | The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1). |
| Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State | Week 1 (after first dose) and Week 15 (steady state) | The maximum (peak) observed, serum, drug concentration after single or multiple dose administration (mass x volume-1) |
| Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab After First Dose - Part A - AUCd15 | Day 1 to Day 15 | The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) following the first dose. AUCd15 was calculated based on P-selectin inhibition curves. |
| Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab - Part A - AUCtau After Multiple Dose - Steady State | Week 15 - Steady state | The AUC of %inhibition calculated to the end of a dosing interval (tau) after multiple dose. AUCtau was calculated based on P-selectin inhibition curves. |
| Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Adverse events are reported from the first dose of study treatment until end of study treatment Week 103 plus 105 days post-treatment follow-up, up to a maximum timeframe of approximately 2 years and 3.25 months. | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Splenic Sequestration | Up to Year 2 | VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B) Splenic sequestration if defined on the basis of findings of left upper quadrant pain, an enlarged spleen, and an acute decrease in hemoglobin concentration (e.g., a decrease in hemoglobin of \ 2 g/dL). Acute splenic sequestration will be considered resolved when left upper quadrant pain has returned to baseline (pre-event) levels and hemoglobin has been stable for 24 hrs. |
| Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Priapism | Up to Year 2 | VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B) Priapism is defined as an unwanted or painful penile erection lasting at least 30 minutes. The end of an acute priapism event will be when the unwanted erection has resolved for at least 2 hours. |
| Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related) | Up to Year 2 | VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This rate was calculated by multiplying the number of hospitalizations and ER visits (VOC-related) by 365 and dividing by the number of days in the observation period. Units would be something like: hospitalizations and ER visits per year. (Parts A and B) |
| Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total) | Up to Year 2 | VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. The baseline annualized rate of VOC was defined as the number of VOCs leading to healthcare visit occurring within the last 12 months prior to screening until first dose. This rate was calculated by multiplying the number of hospitalizations and ER visits (VOC-related) by 365 and dividing by the number of days in the observation period. Units would be something like: hospitalizations and ER visits per year. (Parts A and B) |
| Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Years 1 and 2 | VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. The baseline annualized rate of VOC was defined as the number of VOCs leading to healthcare visit occurring within the last 12 months prior to screening until first dose. This rate was calculated by multiplying the number of days of ER/hospitalizations (both overall and VOC-related) by 365 and dividing by the number of days in the observation period. (Parts A and B) |
| Absolute Change From Baseline in Hemoglobin | Baseline, Week 27, Year 2 | Hemoglobin is a protein that carries oxygen through the body. It attaches to red blood cells, delivers oxygen throughout the body, and transports carbon dioxide back to the lungs. In sickle cell disease, red blood cells are crescent or sickle-shaped due to a genetic mutation, and those sickled red blood cells can clog blood flow, causing debilitating pain and even organ damage. |
| Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | up to Year 2 | Anti-drug antibodies (ADA) are antibodies elicited from therapeutics and they are used to measure immunogenicity. |
| Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Baseline, Year 1 and Year 2 | VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. The baseline annualized rate of VOC was defined as the number of VOCs leading to healthcare visit occurring within the last 12 months prior to screening until first dose. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B) |
| Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Female Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Week 51 | As assessed per Tanner criteria. The number of Participants Analyzed row refer to participants who have not started puberty and have not had delayed puberty prior to start date of study treatment. Delayed puberty in females is defined as failure to attain Tanner Stage 2 (for both breast development and pubic hair) by age 13, or absence of menarche by age 15 or within 5 years of attainment of Tanner Stage 2. |
| Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Week 51 | As assessed per Tanner criteria. The number of Participants Analyzed row refer to participants who have not started puberty and have not had delayed puberty prior to start date of study treatment. Delayed puberty in males is defined as failure to attain Tanner Stage 2 (for both genitalia and pubic hair) by age 14. |
| PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 3, Week 7, Week 11, Week 15, Week 19, Week 23, Week 27, Week 31, Week 35, Week 39, Week 43, Week 47 and Week 51 (Day 1, 0 hr (pre-dose)) | — |
| PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 3, Week 7, Week 11, Week 15, Week 19, Week 23, Week 27, Week 31, Week 35, Week 39, Week 43, Week 47 and Week 51 (0 hr (pre-dose)) | — |
| Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Weeks 3, 7, 11,15, 19, 23, 27, 31, 35, 39, 43,47,51 (Day 1, 0 hr (pre-dose)) | A PD marker of crizanlizumab is the ex vivo P-selectin inhibition measured by a surface plasmon resonance assay using human serum samples. Crizanlizumab in serum samples binds to spiked Psel-Ig (P-selectin coupled to Ig) and inhibits its binding to a PSGL1 peptide. |
| Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Weeks 3, 7, 11,15, 19, 23, 27, 31, 35, 39, 43,47,51 (Day 1, 0 hr (pre-dose)) | A PD marker of crizanlizumab is the ex vivo P-selectin inhibition measured by a surface plasmon resonance assay using human serum samples. Crizanlizumab in serum samples binds to spiked Psel-Ig (P-selectin coupled to Ig) and inhibits its binding to a PSGL1 peptide. |
| Adverse Events by Preferred Term Related to Study Treatment | Adverse events are reported from the first dose of study treatment until end of study treatment Week 103 plus 105 days post-treatment follow-up, up to a maximum timeframe of approximately 2 years and 3.25 months. | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject |
| Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | Baseline, up to Year 2 | QTcF = QT interval corrected by Fridericia's formula QTcB = Corrected QT interval Bazett's Formula QT = QT interval PR = PR interval QRS = QRS interval RR = RR interval HR = heart rate |
| Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient) | Up to Year 2 | VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B) |
| Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Uncomplicated Pain Crisis | Up to Year 2 | VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B) Uncomplicated pain crisis is defined as an acute episode of pain with no known cause for pain other than a vaso-occlusive event; and requiring treatment with a parenteral or oral opioids or other parenteral analgesic; but is NOT classified as an acute chest syndrome, hepatic sequestration, splenic sequestration or priapism. The end of an uncomplicated pain crisis will be considered the resolution of acute pain, such that residual pain (or absence of any pain) is considered to be chronic, and the current pain medication regimen is considered to be for this chronic pain. |
| Annualized Rate of Dactylitis Events | On Treatment, up to Year 2 | Dactylitis, also known as 'hand-foot syndrome', is a complication of acute vaso-occlusive disease characterized by pain and edema of the digits as well as the dorsum of the hands or feet, or both simultaneously, often accompanied by increased local temperature and erythema. There were no patients with dactylitis events. Therefore, there were no observations which met the report criteria. |
| Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Acute Chest Syndrome | Up to Year 2 | VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B) Acute Chest Syndrome (ACS) is defined on the basis of the finding of a new pulmonary infiltrate involving at least one complete lung segment that was consistent with alveolar consolidation, but excluding atelectasis (as indicated by chest X-ray). At least one of the following additional signs or symptoms needs to be present as well: chest pain, a temperature of more than 38.5°C, tachypnea, wheezing or cough. ACS will be considered resolved when the patient is no longer hospitalized (unless for reason other than the ACS episode) and none of the additional signs or symptoms above are present (unless for reason other than the ACS). |
| Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient) - Hepatic Sequestration | Up to Year 2 | VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B) Hepatic sequestration is defined on the basis of findings of right upper quadrant pain, an enlarged liver, and an acute decrease in hemoglobin concentration (e.g. a decrease in hemoglobin of \ 2 g/dL). Acute hepatic sequestration will be considered resolved when right upper quadrant pain has returned to baseline (pre-event) levels and hemoglobin has been stable for 24 hrs. There were no patients with VOC events of hepatic sequestration treated at home. Therefore, there were no observations which met the report criteria. |
Countries
Belgium, Brazil, Canada, Colombia, France, Germany, India, Italy, Lebanon, Oman, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Age 12 to <18 Years, 5 mg/kg Age 12 to \<18 years, 5 mg/kg | 50 |
| Age 6 to <12 Years, 5 mg/kg Age 6 to \<12 years, 5 mg/kg | 13 |
| Age 6 to <12 Years, 8.5 mg/kg Age 6 to \<12 years, 8.5 mg/kg | 40 |
| Age 2 to <6 Years, 8.5 mg/kg Age 2 to \<6 years, 8.5 mg/kg | 14 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 1 |
| Overall Study | Death | 1 | 0 | 0 | 0 |
| Overall Study | Guardian Decision | 4 | 2 | 7 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Participant Decision | 7 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 3 | 1 | 2 | 0 |
| Overall Study | Pregnancy | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Age 12 to <18 Years, 5 mg/kg | Age 6 to <12 Years, 5 mg/kg | Age 6 to <12 Years, 8.5 mg/kg | Age 2 to <6 Years, 8.5 mg/kg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 50 Participants | 13 Participants | 40 Participants | 14 Participants | 117 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 15.00 Years STANDARD_DEVIATION 1.921 | 8.87 Years STANDARD_DEVIATION 1.745 | 9.29 Years STANDARD_DEVIATION 1.614 | 4.81 Years STANDARD_DEVIATION 0.868 | 11.15 Years STANDARD_DEVIATION 3.983 |
| Age, Customized 0 - <28 d | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 12 y - <18 y | 50 Participants | 0 Participants | 0 Participants | 0 Participants | 50 Participants |
| Age, Customized 28 d - <2 y | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 2 y - <12 y | 0 Participants | 13 Participants | 40 Participants | 14 Participants | 67 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 0 Participants | 3 Participants | 0 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 7 Participants | 19 Participants | 8 Participants | 66 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 4 Participants | 13 Participants | 2 Participants | 30 Participants |
| Sex: Female, Male Female | 29 Participants | 5 Participants | 17 Participants | 5 Participants | 56 Participants |
| Sex: Female, Male Male | 21 Participants | 8 Participants | 23 Participants | 9 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 50 | 0 / 13 | 0 / 40 | 0 / 14 | 1 / 117 |
| other Total, other adverse events | 46 / 50 | 13 / 13 | 36 / 40 | 13 / 14 | 108 / 117 |
| serious Total, serious adverse events | 18 / 50 | 9 / 13 | 20 / 40 | 12 / 14 | 59 / 117 |
Outcome results
Primary
Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject
Time frame: Adverse events are reported from the first dose of study treatment until end of study treatment Week 103 plus 105 days post-treatment follow-up, up to a maximum timeframe of approximately 2 years and 3.25 months.
Population: Safety analysis set - all treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs -Treatment-related | 16 Participants |
| Age 12 to <18 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs requiring additional therapy | 45 Participants |
| Age 12 to <18 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Serious Adverse events (SAEs) | 18 Participants |
| Age 12 to <18 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Adverse events (AEs) | 47 Participants |
| Age 12 to <18 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs leading to dose interruption/reduction | 17 Participants |
| Age 12 to <18 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Fatal SAEs | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Fatal SAEs-Treatment-related | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | SAEs -Treatment-related | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs -Treatment-related | 5 Participants |
| Age 6 to <12 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Serious Adverse events (SAEs) | 9 Participants |
| Age 6 to <12 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs leading to dose interruption/reduction | 6 Participants |
| Age 6 to <12 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs requiring additional therapy | 13 Participants |
| Age 6 to <12 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Adverse events (AEs) | 13 Participants |
| Age 6 to <12 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | SAEs -Treatment-related | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Fatal SAEs | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Fatal SAEs-Treatment-related | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Fatal SAEs-Treatment-related | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Fatal SAEs | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | SAEs -Treatment-related | 2 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs leading to dose interruption/reduction | 10 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Serious Adverse events (SAEs) | 20 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs requiring additional therapy | 37 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs -Treatment-related | 14 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Adverse events (AEs) | 38 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Fatal SAEs-Treatment-related | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs leading to dose interruption/reduction | 7 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Serious Adverse events (SAEs) | 12 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | SAEs -Treatment-related | 1 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Adverse events (AEs) | 14 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | Fatal SAEs | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs -Treatment-related | 4 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability | AEs requiring additional therapy | 14 Participants |
Primary
Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab After First Dose - Part A - AUCd15
The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) following the first dose. AUCd15 was calculated based on P-selectin inhibition curves.
Time frame: Day 1 to Day 15
Population: Pharmacodynamic analysis set 1 - for treated participants with a valid measurement above the limit of quantitation without a protocol deviation with impact and for measurements that were above the limit of quantitation. (Age 2 to \<6 years, 8.5 mg/kg has n = '0' since the values were below the limit of quantitation (BLQ).)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab After First Dose - Part A - AUCd15 | 33700 hr*{Percent} inhibition P-selectin | Standard Deviation 2440 |
| Age 6 to <12 Years, 5 mg/kg | Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab After First Dose - Part A - AUCd15 | 34400 hr*{Percent} inhibition P-selectin | Standard Deviation 3660 |
| Age 6 to <12 Years, 8.5 mg/kg | Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab After First Dose - Part A - AUCd15 | 33200 hr*{Percent} inhibition P-selectin | Standard Deviation 3410 |
Primary
Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab - Part A - AUCtau After Multiple Dose - Steady State
The AUC of %inhibition calculated to the end of a dosing interval (tau) after multiple dose. AUCtau was calculated based on P-selectin inhibition curves.
Time frame: Week 15 - Steady state
Population: Pharmacokinetic analysis set 1 - for treated participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab - Part A - AUCtau After Multiple Dose - Steady State | 66700 hr*{Percent} inhibition P-selectin | Standard Deviation 9560 |
| Age 6 to <12 Years, 5 mg/kg | Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab - Part A - AUCtau After Multiple Dose - Steady State | 64800 hr*{Percent} inhibition P-selectin | Standard Deviation 3550 |
| Age 6 to <12 Years, 8.5 mg/kg | Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab - Part A - AUCtau After Multiple Dose - Steady State | 68600 hr*{Percent} inhibition P-selectin | Standard Deviation 9210 |
| Age 2 to <6 Years, 8.5 mg/kg | Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab - Part A - AUCtau After Multiple Dose - Steady State | 66300 hr*{Percent} inhibition P-selectin | Standard Deviation 5710 |
Primary
Pharmacokinetics (PK): AUCd15 of Crizanlizumab After First Dose - Part A
The area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) following the first dose. AUCd15 was calculated based on serum concentrations of crizanlizumab.
Time frame: Day 1 to Day 15
Population: Pharmacokinetic analysis set 1 - for treated participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Pharmacokinetics (PK): AUCd15 of Crizanlizumab After First Dose - Part A | 10500 hr*ug/mL | Standard Deviation 2290 |
| Age 6 to <12 Years, 5 mg/kg | Pharmacokinetics (PK): AUCd15 of Crizanlizumab After First Dose - Part A | 8180 hr*ug/mL | Standard Deviation 1620 |
| Age 6 to <12 Years, 8.5 mg/kg | Pharmacokinetics (PK): AUCd15 of Crizanlizumab After First Dose - Part A | 20600 hr*ug/mL | Standard Deviation 4530 |
| Age 2 to <6 Years, 8.5 mg/kg | Pharmacokinetics (PK): AUCd15 of Crizanlizumab After First Dose - Part A | 14400 hr*ug/mL | Standard Deviation 3990 |
Primary
Pharmacokinetics (PK) - AUCtau for Serum Crizanlizumab After Multiple Doses - Part A - Steady State
The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).
Time frame: Week 15 - Steady state
Population: Pharmacokinetic analysis set 1 - for treated participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Pharmacokinetics (PK) - AUCtau for Serum Crizanlizumab After Multiple Doses - Part A - Steady State | 15800 hr*ug/mL | Standard Deviation 2080 |
| Age 6 to <12 Years, 5 mg/kg | Pharmacokinetics (PK) - AUCtau for Serum Crizanlizumab After Multiple Doses - Part A - Steady State | 14800 hr*ug/mL | Standard Deviation 3770 |
| Age 6 to <12 Years, 8.5 mg/kg | Pharmacokinetics (PK) - AUCtau for Serum Crizanlizumab After Multiple Doses - Part A - Steady State | 35700 hr*ug/mL | Standard Deviation 8100 |
| Age 2 to <6 Years, 8.5 mg/kg | Pharmacokinetics (PK) - AUCtau for Serum Crizanlizumab After Multiple Doses - Part A - Steady State | 22100 hr*ug/mL | Standard Deviation 6200 |
Primary
Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State
The maximum (peak) observed, serum, drug concentration after single or multiple dose administration (mass x volume-1)
Time frame: Week 1 (after first dose) and Week 15 (steady state)
Population: Pharmacokinetic analysis set 1 - for treated participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State | PK Single Dose (Week 1) (n=11,11,13,10) | 80.5 ug/mL | Standard Deviation 17.7 |
| Age 12 to <18 Years, 5 mg/kg | Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State | PK Multiple Dose - Week 15 (Steady state) (n=7,8,12,12) | 95.6 ug/mL | Standard Deviation 26.6 |
| Age 6 to <12 Years, 5 mg/kg | Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State | PK Multiple Dose - Week 15 (Steady state) (n=7,8,12,12) | 77.5 ug/mL | Standard Deviation 19 |
| Age 6 to <12 Years, 5 mg/kg | Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State | PK Single Dose (Week 1) (n=11,11,13,10) | 65.9 ug/mL | Standard Deviation 11.3 |
| Age 6 to <12 Years, 8.5 mg/kg | Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State | PK Single Dose (Week 1) (n=11,11,13,10) | 175 ug/mL | Standard Deviation 36 |
| Age 6 to <12 Years, 8.5 mg/kg | Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State | PK Multiple Dose - Week 15 (Steady state) (n=7,8,12,12) | 171 ug/mL | Standard Deviation 35.3 |
| Age 2 to <6 Years, 8.5 mg/kg | Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State | PK Single Dose (Week 1) (n=11,11,13,10) | 110 ug/mL | Standard Deviation 37.3 |
| Age 2 to <6 Years, 8.5 mg/kg | Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State | PK Multiple Dose - Week 15 (Steady state) (n=7,8,12,12) | 111 ug/mL | Standard Deviation 27.4 |
Secondary
Absolute Change From Baseline in Hemoglobin
Hemoglobin is a protein that carries oxygen through the body. It attaches to red blood cells, delivers oxygen throughout the body, and transports carbon dioxide back to the lungs. In sickle cell disease, red blood cells are crescent or sickle-shaped due to a genetic mutation, and those sickled red blood cells can clog blood flow, causing debilitating pain and even organ damage.
Time frame: Baseline, Week 27, Year 2
Population: Safety analysis set - for treated participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Absolute Change From Baseline in Hemoglobin | Week 27 | -1.26 g/L | Standard Deviation 11.472 |
| Age 12 to <18 Years, 5 mg/kg | Absolute Change From Baseline in Hemoglobin | End Of Treatment / Year 2 (n=24,6,11,2) | -5.38 g/L | Standard Deviation 11.088 |
| Age 6 to <12 Years, 5 mg/kg | Absolute Change From Baseline in Hemoglobin | End Of Treatment / Year 2 (n=24,6,11,2) | 2.33 g/L | Standard Deviation 7.941 |
| Age 6 to <12 Years, 5 mg/kg | Absolute Change From Baseline in Hemoglobin | Week 27 | 2.33 g/L | Standard Deviation 6.856 |
| Age 6 to <12 Years, 8.5 mg/kg | Absolute Change From Baseline in Hemoglobin | Week 27 | -0.33 g/L | Standard Deviation 7.015 |
| Age 6 to <12 Years, 8.5 mg/kg | Absolute Change From Baseline in Hemoglobin | End Of Treatment / Year 2 (n=24,6,11,2) | -1.18 g/L | Standard Deviation 11.677 |
| Age 2 to <6 Years, 8.5 mg/kg | Absolute Change From Baseline in Hemoglobin | Week 27 | 1.55 g/L | Standard Deviation 9.905 |
| Age 2 to <6 Years, 8.5 mg/kg | Absolute Change From Baseline in Hemoglobin | End Of Treatment / Year 2 (n=24,6,11,2) | 15.00 g/L | Standard Deviation 1.414 |
Secondary
Adverse Events by Preferred Term Related to Study Treatment
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject
Time frame: Adverse events are reported from the first dose of study treatment until end of study treatment Week 103 plus 105 days post-treatment follow-up, up to a maximum timeframe of approximately 2 years and 3.25 months.
Population: Safety analysis set - all treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Malaise | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Sacral pain | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Abdominal pain | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Hot flush | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Agitation | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Number of participants with at least one event | 16 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Hypersensitivity | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Alopecia | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Anaemia | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Blood creatine phosphokinase increased | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Fatigue | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Dyspnoea | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Infusion related reaction | 5 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Vascular access complication | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pyrexia | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Back pain | 3 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Vomiting | 2 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Nausea | 3 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pain in extremity | 2 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Asthenia | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pruritus | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Sickle cell anaemia with crisis | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Spinal pain | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Paraesthesia | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Arthralgia | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Blood bilirubin increased | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Conjunctivitis | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Dizziness | 2 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Neck pain | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Headache | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Infusion site pain | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Muscle fatigue | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Myalgia | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pain | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Neutropenia | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pruritus | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Vascular access complication | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Dizziness | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pain in extremity | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Abdominal pain | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Sacral pain | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Hypersensitivity | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Myalgia | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Agitation | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Fatigue | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Sickle cell anaemia with crisis | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Paraesthesia | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Alopecia | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Number of participants with at least one event | 5 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Hot flush | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Headache | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Anaemia | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Asthenia | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Vomiting | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pyrexia | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Blood creatine phosphokinase increased | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Muscle fatigue | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Arthralgia | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Dyspnoea | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Malaise | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Infusion related reaction | 2 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Neck pain | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pain | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Conjunctivitis | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Back pain | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Infusion site pain | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Blood bilirubin increased | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Neutropenia | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Nausea | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Spinal pain | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pruritus | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Infusion site pain | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Anaemia | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Blood creatine phosphokinase increased | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Fatigue | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Number of participants with at least one event | 14 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Infusion related reaction | 3 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Back pain | 4 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Nausea | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pain in extremity | 2 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Sickle cell anaemia with crisis | 2 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Arthralgia | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Conjunctivitis | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Dizziness | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Headache | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Myalgia | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Neutropenia | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pain | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Vomiting | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Abdominal pain | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Agitation | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Alopecia | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Asthenia | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Blood bilirubin increased | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Dyspnoea | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Hot flush | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Hypersensitivity | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Malaise | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Muscle fatigue | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Neck pain | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Paraesthesia | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pyrexia | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Sacral pain | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Spinal pain | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Vascular access complication | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Myalgia | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Asthenia | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Malaise | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Infusion site pain | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Headache | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Anaemia | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Muscle fatigue | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Dizziness | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Arthralgia | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Vascular access complication | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Neck pain | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Sickle cell anaemia with crisis | 1 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Conjunctivitis | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Spinal pain | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Paraesthesia | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pain in extremity | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Nausea | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Back pain | 2 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pruritus | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Infusion related reaction | 1 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Number of participants with at least one event | 4 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Vomiting | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pyrexia | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Fatigue | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Blood bilirubin increased | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Dyspnoea | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Blood creatine phosphokinase increased | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Alopecia | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Pain | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Hot flush | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Agitation | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Abdominal pain | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Sacral pain | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Hypersensitivity | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Adverse Events by Preferred Term Related to Study Treatment | Neutropenia | 1 Participants |
Secondary
Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related)
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. The baseline annualized rate of VOC was defined as the number of VOCs leading to healthcare visit occurring within the last 12 months prior to screening until first dose. This rate was calculated by multiplying the number of days of ER/hospitalizations (both overall and VOC-related) by 365 and dividing by the number of days in the observation period. (Parts A and B)
Time frame: Years 1 and 2
Population: Full analysis set - for treated participants with a valid measurement without a protocol deviation with impact who had ER/hospitalizations.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 2 - VOC related (n=32,10,11, 10) | 10.50 Days per year |
| Age 12 to <18 Years, 5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 1 - VOC related (n=42,11,12, 12) | 7.00 Days per year |
| Age 12 to <18 Years, 5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 1 - Total (n=42,11,12, 12) | 7.00 Days per year |
| Age 12 to <18 Years, 5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization on treatment - Total (up to Year 2) | 12.37 Days per year |
| Age 12 to <18 Years, 5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization on treatment - VOC related (up to Year 2) | 6.74 Days per year |
| Age 12 to <18 Years, 5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 2 - Total (n=32,10,11, 10) | 13.00 Days per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 1 - Total (n=42,11,12, 12) | 2.00 Days per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization on treatment - VOC related (up to Year 2) | 0.98 Days per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization on treatment - Total (up to Year 2) | 5.41 Days per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 2 - VOC related (n=32,10,11, 10) | 0.00 Days per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 2 - Total (n=32,10,11, 10) | 2.00 Days per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 1 - VOC related (n=42,11,12, 12) | 0.00 Days per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 1 - Total (n=42,11,12, 12) | 11.00 Days per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 2 - VOC related (n=32,10,11, 10) | 2.00 Days per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization on treatment - Total (up to Year 2) | 9.03 Days per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization on treatment - VOC related (up to Year 2) | 5.36 Days per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 2 - Total (n=32,10,11, 10) | 3.00 Days per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 1 - VOC related (n=42,11,12, 12) | 5.00 Days per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 1 - VOC related (n=42,11,12, 12) | 0.00 Days per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization on treatment - Total (up to Year 2) | 10.48 Days per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization on treatment - VOC related (up to Year 2) | 2.20 Days per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 1 - Total (n=42,11,12, 12) | 6.50 Days per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 2 - VOC related (n=32,10,11, 10) | 3.00 Days per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related) | Annualized days of ER/Hospitalization Year 2 - Total (n=32,10,11, 10) | 10.50 Days per year |
Secondary
Annualized Rate of Dactylitis Events
Dactylitis, also known as 'hand-foot syndrome', is a complication of acute vaso-occlusive disease characterized by pain and edema of the digits as well as the dorsum of the hands or feet, or both simultaneously, often accompanied by increased local temperature and erythema. There were no patients with dactylitis events. Therefore, there were no observations which met the report criteria.
Time frame: On Treatment, up to Year 2
Population: Safety analysis set - all treated participants who had dactylitis events. There were no observations which met the report criteria.
Secondary
Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total)
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. The baseline annualized rate of VOC was defined as the number of VOCs leading to healthcare visit occurring within the last 12 months prior to screening until first dose. This rate was calculated by multiplying the number of hospitalizations and ER visits (VOC-related) by 365 and dividing by the number of days in the observation period. Units would be something like: hospitalizations and ER visits per year. (Parts A and B)
Time frame: Up to Year 2
Population: Full analysis set - for treated participants with a valid measurement without a protocol deviation with impact who had hospitalizations and ER visits.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total) | Annualized rate of hospitalizations and ER visits Year 1 (n=42,11,35,12) | 2.00 hospitalizations and ER visits per year |
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total) | Annualized rate of hospitalizations and ER visits Year 2 (n=32,10,27,10) | 2.50 hospitalizations and ER visits per year |
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total) | Annualized rate of hospitalizations and ER visits (up to Year 2) | 2.68 hospitalizations and ER visits per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total) | Annualized rate of hospitalizations and ER visits Year 2 (n=32,10,27,10) | 1.00 hospitalizations and ER visits per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total) | Annualized rate of hospitalizations and ER visits Year 1 (n=42,11,35,12) | 1.00 hospitalizations and ER visits per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total) | Annualized rate of hospitalizations and ER visits (up to Year 2) | 1.46 hospitalizations and ER visits per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total) | Annualized rate of hospitalizations and ER visits Year 2 (n=32,10,27,10) | 1.00 hospitalizations and ER visits per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total) | Annualized rate of hospitalizations and ER visits (up to Year 2) | 1.59 hospitalizations and ER visits per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total) | Annualized rate of hospitalizations and ER visits Year 1 (n=42,11,35,12) | 2.00 hospitalizations and ER visits per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total) | Annualized rate of hospitalizations and ER visits (up to Year 2) | 1.74 hospitalizations and ER visits per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total) | Annualized rate of hospitalizations and ER visits Year 1 (n=42,11,35,12) | 2.00 hospitalizations and ER visits per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total) | Annualized rate of hospitalizations and ER visits Year 2 (n=32,10,27,10) | 2.00 hospitalizations and ER visits per year |
Secondary
Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related)
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This rate was calculated by multiplying the number of hospitalizations and ER visits (VOC-related) by 365 and dividing by the number of days in the observation period. Units would be something like: hospitalizations and ER visits per year. (Parts A and B)
Time frame: Up to Year 2
Population: Full analysis set - for treated participants with a valid measurement without a protocol deviation with impact who had hospitalizations and ER visits (VOC-related).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related) | Annualized rate of hospitalizations and ER visits (up to Year 2) | 1.78 hospitalizations and ER visits per year |
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related) | Annualized rate of hospitalizations and ER visits Year 2 (n=32,10,27,10) | 2.00 hospitalizations and ER visits per year |
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related) | Annualized rate of hospitalizations and ER visits Year 1 (n=42,11,35,12) | 2.00 hospitalizations and ER visits per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related) | Annualized rate of hospitalizations and ER visits Year 1 (n=42,11,35,12) | 0.00 hospitalizations and ER visits per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related) | Annualized rate of hospitalizations and ER visits Year 2 (n=32,10,27,10) | 0.00 hospitalizations and ER visits per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related) | Annualized rate of hospitalizations and ER visits (up to Year 2) | 0.50 hospitalizations and ER visits per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related) | Annualized rate of hospitalizations and ER visits Year 2 (n=32,10,27,10) | 1.00 hospitalizations and ER visits per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related) | Annualized rate of hospitalizations and ER visits (up to Year 2) | 1.01 hospitalizations and ER visits per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related) | Annualized rate of hospitalizations and ER visits Year 1 (n=42,11,35,12) | 1.00 hospitalizations and ER visits per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related) | Annualized rate of hospitalizations and ER visits (up to Year 2) | 0.74 hospitalizations and ER visits per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related) | Annualized rate of hospitalizations and ER visits Year 2 (n=32,10,27,10) | 1.00 hospitalizations and ER visits per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related) | Annualized rate of hospitalizations and ER visits Year 1 (n=42,11,35,12) | 0.00 hospitalizations and ER visits per year |
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Acute Chest Syndrome
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B) Acute Chest Syndrome (ACS) is defined on the basis of the finding of a new pulmonary infiltrate involving at least one complete lung segment that was consistent with alveolar consolidation, but excluding atelectasis (as indicated by chest X-ray). At least one of the following additional signs or symptoms needs to be present as well: chest pain, a temperature of more than 38.5°C, tachypnea, wheezing or cough. ACS will be considered resolved when the patient is no longer hospitalized (unless for reason other than the ACS episode) and none of the additional signs or symptoms above are present (unless for reason other than the ACS).
Time frame: Up to Year 2
Population: Full analysis set - for treated participants with acute chest syndrome without a protocol deviation with impact who had VOC events leading to healthcare visit - acute chest syndrome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Acute Chest Syndrome | 0.49 VOC events per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Acute Chest Syndrome | 0.64 VOC events per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Acute Chest Syndrome | 0.49 VOC events per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Acute Chest Syndrome | 0.49 VOC events per year |
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. The baseline annualized rate of VOC was defined as the number of VOCs leading to healthcare visit occurring within the last 12 months prior to screening until first dose. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Time frame: Baseline, Year 1 and Year 2
Population: Full analysis set - for treated participants with a valid measurement without a protocol deviation with impact who had VOC events leading to healthcare visit in clinic/ER/hospital.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Baseline annualized rate of VOC | 3.00 VOC events per year |
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Annualized rate of VOC on treatment Year 1 (n=42,11,35,12) | 2.00 VOC events per year |
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Annualized rate of VOC on treatment (up to Year 2) | 1.80 VOC events per year |
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Annualized rate of VOC on treatment Year 2 (n=32,10,27,10) | 2.00 VOC events per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Baseline annualized rate of VOC | 1.00 VOC events per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Annualized rate of VOC on treatment Year 2 (n=32,10,27,10) | 0.00 VOC events per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Annualized rate of VOC on treatment (up to Year 2) | 0.79 VOC events per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Annualized rate of VOC on treatment Year 1 (n=42,11,35,12) | 0.00 VOC events per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Annualized rate of VOC on treatment Year 2 (n=32,10,27,10) | 1.00 VOC events per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Annualized rate of VOC on treatment Year 1 (n=42,11,35,12) | 1.00 VOC events per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Annualized rate of VOC on treatment (up to Year 2) | 1.48 VOC events per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Baseline annualized rate of VOC | 2.00 VOC events per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Baseline annualized rate of VOC | 1.00 VOC events per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Annualized rate of VOC on treatment Year 1 (n=42,11,35,12) | 0.00 VOC events per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Annualized rate of VOC on treatment (up to Year 2) | 1.22 VOC events per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital | Annualized rate of VOC on treatment Year 2 (n=32,10,27,10) | 2.00 VOC events per year |
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Priapism
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B) Priapism is defined as an unwanted or painful penile erection lasting at least 30 minutes. The end of an acute priapism event will be when the unwanted erection has resolved for at least 2 hours.
Time frame: Up to Year 2
Population: Full analysis set - for treated participants with priapism and with a valid measurement above the limit of quantitation without a protocol deviation with impact who had VOC events leading to healthcare visit - priapism. (No patients in the 1st and 4th group met this criteria.)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Priapism | 0.49 VOC events per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Priapism | 0.00 VOC events per year |
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Splenic Sequestration
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B) Splenic sequestration if defined on the basis of findings of left upper quadrant pain, an enlarged spleen, and an acute decrease in hemoglobin concentration (e.g., a decrease in hemoglobin of \ 2 g/dL). Acute splenic sequestration will be considered resolved when left upper quadrant pain has returned to baseline (pre-event) levels and hemoglobin has been stable for 24 hrs.
Time frame: Up to Year 2
Population: Full analysis set - for treated participants with splenic sequestration with a valid measurement and without a protocol deviation with impact who had VOC events leading to healthcare visit - splenic sequestration. (No patients in the 4th group met this criteria.)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Splenic Sequestration | 0.00 VOC events per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Splenic Sequestration | 0.00 VOC events per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Splenic Sequestration | 0.00 VOC events per year |
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Uncomplicated Pain Crisis
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B) Uncomplicated pain crisis is defined as an acute episode of pain with no known cause for pain other than a vaso-occlusive event; and requiring treatment with a parenteral or oral opioids or other parenteral analgesic; but is NOT classified as an acute chest syndrome, hepatic sequestration, splenic sequestration or priapism. The end of an uncomplicated pain crisis will be considered the resolution of acute pain, such that residual pain (or absence of any pain) is considered to be chronic, and the current pain medication regimen is considered to be for this chronic pain.
Time frame: Up to Year 2
Population: Full analysis set - for treated participants with uncomplicated pain crisis without a protocol deviation with impact who had VOC events leading to healthcare visit - uncomplicated pain crisis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Uncomplicated Pain Crisis | 1.79 VOC events per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Uncomplicated Pain Crisis | 0.98 VOC events per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Uncomplicated Pain Crisis | 1.47 VOC events per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Uncomplicated Pain Crisis | 0.97 VOC events per year |
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient)
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Time frame: Up to Year 2
Population: Full analysis set - for treated participants with a valid measurement without a protocol deviation with impact who had VOC events treated at home (based on documentation by health care provider following phone contact with the patient.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient) | 0.94 VOC events per year |
| Age 6 to <12 Years, 5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient) | 2.71 VOC events per year |
| Age 6 to <12 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient) | 0.49 VOC events per year |
| Age 2 to <6 Years, 8.5 mg/kg | Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient) | 0.73 VOC events per year |
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient) - Hepatic Sequestration
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration. This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B) Hepatic sequestration is defined on the basis of findings of right upper quadrant pain, an enlarged liver, and an acute decrease in hemoglobin concentration (e.g. a decrease in hemoglobin of \ 2 g/dL). Acute hepatic sequestration will be considered resolved when right upper quadrant pain has returned to baseline (pre-event) levels and hemoglobin has been stable for 24 hrs. There were no patients with VOC events of hepatic sequestration treated at home. Therefore, there were no observations which met the report criteria.
Time frame: Up to Year 2
Population: Full analysis set - for treated participants with hepatic sequestration without a protocol deviation with impact who had VOC events treated at home (based on documentation by health care provider following phone contact with the patient) - hepatic sequestration. There were no observations which met this criteria.
Secondary
Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Female Participants at Risk of Delayed Puberty at Start Date of Study Treatment
As assessed per Tanner criteria. The number of Participants Analyzed row refer to participants who have not started puberty and have not had delayed puberty prior to start date of study treatment. Delayed puberty in females is defined as failure to attain Tanner Stage 2 (for both breast development and pubic hair) by age 13, or absence of menarche by age 15 or within 5 years of attainment of Tanner Stage 2.
Time frame: Week 51
Population: Full analysis set - only for participants at risk of delayed puberty, (i.e., excludes participants who already reached puberty at study start.)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Age 6 to <12 Years, 5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Female Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = no | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Female Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = yes | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Female Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = unknown (i.e., not applicable because pt not yet in age range for puberty) | 3 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Female Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = no | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Female Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = yes | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Female Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = unknown (i.e., not applicable because pt not yet in age range for puberty) | 12 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Female Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = yes | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Female Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = unknown (i.e., not applicable because pt not yet in age range for puberty) | 5 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Female Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = no | 0 Participants |
Secondary
Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment
As assessed per Tanner criteria. The number of Participants Analyzed row refer to participants who have not started puberty and have not had delayed puberty prior to start date of study treatment. Delayed puberty in males is defined as failure to attain Tanner Stage 2 (for both genitalia and pubic hair) by age 14.
Time frame: Week 51
Population: Full analysis set - only for participants at risk of delayed puberty, (i.e., excludes participants who already reached puberty at study start.)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = yes | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = unknown (i.e., not applicable because pt not yet in age range for puberty) | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = no | 4 Participants |
| Age 6 to <12 Years, 5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = yes | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = unknown (i.e., not applicable because pt not yet in age range for puberty) | 7 Participants |
| Age 6 to <12 Years, 5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = no | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = no | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = yes | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = unknown (i.e., not applicable because pt not yet in age range for puberty) | 18 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = yes | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = unknown (i.e., not applicable because pt not yet in age range for puberty) | 9 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment | Delayed puberty = no | 0 Participants |
Secondary
Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab
Anti-drug antibodies (ADA) are antibodies elicited from therapeutics and they are used to measure immunogenicity.
Time frame: up to Year 2
Population: Full analysis set - for treated participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Baseline - Missing | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Post-baseline - only last sample positive | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Post-baseline - Any positive | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Baseline - Positive | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Baseline - Negative | 50 Participants |
| Age 6 to <12 Years, 5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Post-baseline - only last sample positive | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Baseline - Positive | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Baseline - Missing | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Baseline - Negative | 13 Participants |
| Age 6 to <12 Years, 5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Post-baseline - Any positive | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Baseline - Negative | 39 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Baseline - Missing | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Post-baseline - Any positive | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Baseline - Positive | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Post-baseline - only last sample positive | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Post-baseline - Any positive | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Baseline - Missing | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Baseline - Positive | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Baseline - Negative | 14 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | Post-baseline - only last sample positive | 0 Participants |
Secondary
Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments
QTcF = QT interval corrected by Fridericia's formula QTcB = Corrected QT interval Bazett's Formula QT = QT interval PR = PR interval QRS = QRS interval RR = RR interval HR = heart rate
Time frame: Baseline, up to Year 2
Population: Safety analysis set - for treated participants with a valid measurement without a protocol deviation with impact
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-Increase >60 ms (n=49,13,37,12) | 2 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-New >500 ms (n=49,13,40,13) | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | HR (bpm)-Decrease >25% and HR <50 bpm (n=49,13,37,12) | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QRS (ms)-New QRS >120 ms (n=49,13,40,13) | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-New >480 to <=500 ms (n=49,13,40,13) | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | PR (ms)-New PR >200 ms (n=48,13,40,13) | 2 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-New >480 to <=500 ms (n=49,13,40,13) | 3 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)- New >480 to <=500 ms (n=49,13,40,13) | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | RR (ms)-Increase >25% and RR >1200 ms (n=49,13,37,12) | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-New >500 ms (n=49,13,40,13) | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | PR (ms)-Increase >25% and PR >200 ms (n=48,13,37,12) | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-New >450 to <=480 ms (n=40,12,35,13) | 10 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-New >450 to <=480 ms (n=49,13,40,13) | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QRS (ms)- Increase >25% and QRS >120 ms (n=49,13,37,12) | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)- Increase >60 ms (n=49,13,37,12) | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 13 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)-New >500 ms (n=49,13,40,13) | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)- New >450 to <=480 ms (n=49,13,40,13) | 3 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 12 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | HR (bpm)-Increase >25% and HR >100 bpm (n=49,12,34,7) | 1 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | RR (ms)-Decrease >25% and RR <600 ms (n=49,12,34,7) | 0 Participants |
| Age 12 to <18 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-Increase >60 ms (n=49,13,37,12) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | PR (ms)-Increase >25% and PR >200 ms (n=48,13,37,12) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-Increase >60 ms (n=49,13,37,12) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-New >500 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-New >480 to <=500 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-New >450 to <=480 ms (n=40,12,35,13) | 2 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-New >450 to <=480 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-New >480 to <=500 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-New >500 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)- New >450 to <=480 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | RR (ms)-Decrease >25% and RR <600 ms (n=49,12,34,7) | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 5 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | HR (bpm)-Decrease >25% and HR <50 bpm (n=49,13,37,12) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-Increase >60 ms (n=49,13,37,12) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QRS (ms)- Increase >25% and QRS >120 ms (n=49,13,37,12) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QRS (ms)-New QRS >120 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | RR (ms)-Increase >25% and RR >1200 ms (n=49,13,37,12) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)- New >480 to <=500 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | HR (bpm)-Increase >25% and HR >100 bpm (n=49,12,34,7) | 1 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)- Increase >60 ms (n=49,13,37,12) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | PR (ms)-New PR >200 ms (n=48,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 3 Participants |
| Age 6 to <12 Years, 5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)-New >500 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | PR (ms)-Increase >25% and PR >200 ms (n=48,13,37,12) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)- New >450 to <=480 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)-New >500 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-New >500 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 17 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-Increase >60 ms (n=49,13,37,12) | 2 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QRS (ms)-New QRS >120 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | RR (ms)-Increase >25% and RR >1200 ms (n=49,13,37,12) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 2 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)- New >480 to <=500 ms (n=49,13,40,13) | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 7 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-Increase >60 ms (n=49,13,37,12) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-New >450 to <=480 ms (n=40,12,35,13) | 14 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-New >480 to <=500 ms (n=49,13,40,13) | 1 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-New >450 to <=480 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-New >480 to <=500 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-New >500 ms (n=49,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)- Increase >60 ms (n=49,13,37,12) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | PR (ms)-New PR >200 ms (n=48,13,40,13) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QRS (ms)- Increase >25% and QRS >120 ms (n=49,13,37,12) | 0 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | RR (ms)-Decrease >25% and RR <600 ms (n=49,12,34,7) | 2 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | HR (bpm)-Increase >25% and HR >100 bpm (n=49,12,34,7) | 3 Participants |
| Age 6 to <12 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | HR (bpm)-Decrease >25% and HR <50 bpm (n=49,13,37,12) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | HR (bpm)-Decrease >25% and HR <50 bpm (n=49,13,37,12) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)-New >500 ms (n=49,13,40,13) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | HR (bpm)-Increase >25% and HR >100 bpm (n=49,12,34,7) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | PR (ms)-New PR >200 ms (n=48,13,40,13) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 1 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | PR (ms)-Increase >25% and PR >200 ms (n=48,13,37,12) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)- New >450 to <=480 ms (n=49,13,40,13) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QRS (ms)- Increase >25% and QRS >120 ms (n=49,13,37,12) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-Increase >60 ms (n=49,13,37,12) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QRS (ms)-New QRS >120 ms (n=49,13,40,13) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | RR (ms)-Increase >25% and RR >1200 ms (n=49,13,37,12) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 3 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-New >500 ms (n=49,13,40,13) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)- Increase >60 ms (n=49,13,37,12) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | RR (ms)-Decrease >25% and RR <600 ms (n=49,12,34,7) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-New >480 to <=500 ms (n=49,13,40,13) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-New >480 to <=500 ms (n=49,13,40,13) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-New >450 to <=480 ms (n=49,13,40,13) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-New >450 to <=480 ms (n=40,12,35,13) | 6 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcF (ms)- New >480 to <=500 ms (n=49,13,40,13) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QT (ms)-New >500 ms (n=49,13,40,13) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-Increase >60 ms (n=49,13,37,12) | 0 Participants |
| Age 2 to <6 Years, 8.5 mg/kg | Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments | QTcB (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 1 Participants |
Secondary
Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A
A PD marker of crizanlizumab is the ex vivo P-selectin inhibition measured by a surface plasmon resonance assay using human serum samples. Crizanlizumab in serum samples binds to spiked Psel-Ig (P-selectin coupled to Ig) and inhibits its binding to a PSGL1 peptide.
Time frame: Weeks 3, 7, 11,15, 19, 23, 27, 31, 35, 39, 43,47,51 (Day 1, 0 hr (pre-dose))
Population: Pharmacodynamic analysis set 1 - for treated participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 51 Day 1, 0 hr (pre-dose) (n=5,3,8,7) | 80.9 % inhibition P-selectin | Standard Deviation 34 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 39 Day 1, 0 hr (pre-dose) (n=7,7,8,9) | 80.8 % inhibition P-selectin | Standard Deviation 28 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 23 Day 1, 0 hr (pre-dose) (n=9,10,11,9) | 83.8 % inhibition P-selectin | Standard Deviation 28.9 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 3 Day 1, 0 hr (pre-dose) (n=11,12,13,9) | 100 % inhibition P-selectin | Standard Deviation 0.0924 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 35 Day 1, 0 hr (pre-dose) (n=5,10,8,9) | 97.2 % inhibition P-selectin | Standard Deviation 6.04 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 31 Day 1, 0 hr (pre-dose) (n=6,9,9,9) | 97.8 % inhibition P-selectin | Standard Deviation 2.83 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 47 Day 1, 0 hr (pre-dose) (n=8,2,8,8) | 87.1 % inhibition P-selectin | Standard Deviation 30.5 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 7 Day 1, 0 hr (pre-dose) (n=9,11,12,10) | 99.0 % inhibition P-selectin | Standard Deviation 1.61 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 11 Day 1, 0 hr (pre-dose) (n=9,9,12,9) | 97.7 % inhibition P-selectin | Standard Deviation 4.56 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 43 Day 1, 0 hr (pre-dose) (n=8,3,9,6) | 96.7 % inhibition P-selectin | Standard Deviation 4.19 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 15 Day 1, 0 hr (pre-dose) (n=6,8,11,10) | 96.6 % inhibition P-selectin | Standard Deviation 8.04 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 27 Day 1, 0 hr (pre-dose) (n=9,9,11,8) | 88.0 % inhibition P-selectin | Standard Deviation 25 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 19 Day 1, 0 hr (pre-dose) (n=6,9,12,10) | 88.6 % inhibition P-selectin | Standard Deviation 20.6 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 39 Day 1, 0 hr (pre-dose) (n=7,7,8,9) | 88.6 % inhibition P-selectin | Standard Deviation 25.3 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 7 Day 1, 0 hr (pre-dose) (n=9,11,12,10) | 94.2 % inhibition P-selectin | Standard Deviation 12.2 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 47 Day 1, 0 hr (pre-dose) (n=8,2,8,8) | 98.8 % inhibition P-selectin | Standard Deviation 1.77 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 23 Day 1, 0 hr (pre-dose) (n=9,10,11,9) | 91.2 % inhibition P-selectin | Standard Deviation 14 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 35 Day 1, 0 hr (pre-dose) (n=5,10,8,9) | 92.3 % inhibition P-selectin | Standard Deviation 10.6 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 27 Day 1, 0 hr (pre-dose) (n=9,9,11,8) | 90.8 % inhibition P-selectin | Standard Deviation 20.4 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 43 Day 1, 0 hr (pre-dose) (n=8,3,9,6) | 99.0 % inhibition P-selectin | Standard Deviation 1.67 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 15 Day 1, 0 hr (pre-dose) (n=6,8,11,10) | 99.8 % inhibition P-selectin | Standard Deviation 0.422 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 11 Day 1, 0 hr (pre-dose) (n=9,9,12,9) | 80.8 % inhibition P-selectin | Standard Deviation 32.4 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 31 Day 1, 0 hr (pre-dose) (n=6,9,9,9) | 88.9 % inhibition P-selectin | Standard Deviation 21 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 3 Day 1, 0 hr (pre-dose) (n=11,12,13,9) | 97.9 % inhibition P-selectin | Standard Deviation 2.97 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 51 Day 1, 0 hr (pre-dose) (n=5,3,8,7) | 95.4 % inhibition P-selectin | Standard Deviation 4.24 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 19 Day 1, 0 hr (pre-dose) (n=6,9,12,10) | 83.5 % inhibition P-selectin | Standard Deviation 34.8 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 27 Day 1, 0 hr (pre-dose) (n=9,9,11,8) | 99.4 % inhibition P-selectin | Standard Deviation 1.36 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 23 Day 1, 0 hr (pre-dose) (n=9,10,11,9) | 99.5 % inhibition P-selectin | Standard Deviation 1.24 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 31 Day 1, 0 hr (pre-dose) (n=6,9,9,9) | 99.6 % inhibition P-selectin | Standard Deviation 1.3 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 35 Day 1, 0 hr (pre-dose) (n=5,10,8,9) | 97.9 % inhibition P-selectin | Standard Deviation 3.81 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 51 Day 1, 0 hr (pre-dose) (n=5,3,8,7) | 98.9 % inhibition P-selectin | Standard Deviation 1.86 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 3 Day 1, 0 hr (pre-dose) (n=11,12,13,9) | 99.1 % inhibition P-selectin | Standard Deviation 1.41 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 7 Day 1, 0 hr (pre-dose) (n=9,11,12,10) | 98.5 % inhibition P-selectin | Standard Deviation 3.48 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 15 Day 1, 0 hr (pre-dose) (n=6,8,11,10) | 99.2 % inhibition P-selectin | Standard Deviation 1.86 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 19 Day 1, 0 hr (pre-dose) (n=6,9,12,10) | 99.2 % inhibition P-selectin | Standard Deviation 1.54 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 11 Day 1, 0 hr (pre-dose) (n=9,9,12,9) | 98.5 % inhibition P-selectin | Standard Deviation 2.93 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 39 Day 1, 0 hr (pre-dose) (n=7,7,8,9) | 99.1 % inhibition P-selectin | Standard Deviation 2.01 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 43 Day 1, 0 hr (pre-dose) (n=8,3,9,6) | 98.8 % inhibition P-selectin | Standard Deviation 2.14 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 47 Day 1, 0 hr (pre-dose) (n=8,2,8,8) | 98.1 % inhibition P-selectin | Standard Deviation 3.73 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 19 Day 1, 0 hr (pre-dose) (n=6,9,12,10) | 96.7 % inhibition P-selectin | Standard Deviation 5.51 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 15 Day 1, 0 hr (pre-dose) (n=6,8,11,10) | 91.7 % inhibition P-selectin | Standard Deviation 19.8 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 47 Day 1, 0 hr (pre-dose) (n=8,2,8,8) | 69.8 % inhibition P-selectin | Standard Deviation 44 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 39 Day 1, 0 hr (pre-dose) (n=7,7,8,9) | 87.6 % inhibition P-selectin | Standard Deviation 19.2 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 11 Day 1, 0 hr (pre-dose) (n=9,9,12,9) | 98.4 % inhibition P-selectin | Standard Deviation 2.5 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 7 Day 1, 0 hr (pre-dose) (n=9,11,12,10) | 98.9 % inhibition P-selectin | Standard Deviation 1.91 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 51 Day 1, 0 hr (pre-dose) (n=5,3,8,7) | 92.1 % inhibition P-selectin | Standard Deviation 13 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 43 Day 1, 0 hr (pre-dose) (n=8,3,9,6) | 98.8 % inhibition P-selectin | Standard Deviation 2.37 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 3 Day 1, 0 hr (pre-dose) (n=11,12,13,9) | 98.6 % inhibition P-selectin | Standard Deviation 2.54 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 35 Day 1, 0 hr (pre-dose) (n=5,10,8,9) | 67.4 % inhibition P-selectin | Standard Deviation 42.1 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 31 Day 1, 0 hr (pre-dose) (n=6,9,9,9) | 75.5 % inhibition P-selectin | Standard Deviation 37.9 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 27 Day 1, 0 hr (pre-dose) (n=9,9,11,8) | 85.4 % inhibition P-selectin | Standard Deviation 19.1 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A | Week 23 Day 1, 0 hr (pre-dose) (n=9,10,11,9) | 92.2 % inhibition P-selectin | Standard Deviation 15.7 |
Secondary
Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B
A PD marker of crizanlizumab is the ex vivo P-selectin inhibition measured by a surface plasmon resonance assay using human serum samples. Crizanlizumab in serum samples binds to spiked Psel-Ig (P-selectin coupled to Ig) and inhibits its binding to a PSGL1 peptide.
Time frame: Weeks 3, 7, 11,15, 19, 23, 27, 31, 35, 39, 43,47,51 (Day 1, 0 hr (pre-dose))
Population: Pharmacodynamic analysis set 2 - for treated participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 51 Day 1, 0 hr (pre-dose) (n=27,3,26,9) | 86.4 % inhibition P-selectin | Standard Deviation 25.8 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 23 Day 1, 0 hr (pre-dose) (n=42,11,34,9) | 86.5 % inhibition P-selectin | Standard Deviation 26.3 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 31 Day 1, 0 hr (pre-dose) (n=36,10,32,9) | 90.9 % inhibition P-selectin | Standard Deviation 18.7 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 27 Day 1, 0 hr (pre-dose) (n=37,10,33,9) | 87.6 % inhibition P-selectin | Standard Deviation 26.1 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 47 Day 1, 0 hr (pre-dose) (n=28,2,32,9) | 91.7 % inhibition P-selectin | Standard Deviation 17.7 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 3 Day 1, 0 hr (pre-dose) (n=42,12,36,11) | 99.3 % inhibition P-selectin | Standard Deviation 2.14 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 7 Day 1, 0 hr (pre-dose) (n=41,12,35,12) | 93.7 % inhibition P-selectin | Standard Deviation 17 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 39 Day 1, 0 hr (pre-dose) (n=33,8,33,11) | 85.4 % inhibition P-selectin | Standard Deviation 23.6 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 11 Day 1, 0 hr (pre-dose) (n=41,10,33,10) | 92.7 % inhibition P-selectin | Standard Deviation 17.8 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 15 Day 1, 0 hr (pre-dose) (n=39,9,33,11) | 92.6 % inhibition P-selectin | Standard Deviation 18.9 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 43 Day 1, 0 hr (pre-dose) (n=31,3,32,8) | 93.1 % inhibition P-selectin | Standard Deviation 15.4 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 35 Day 1, 0 hr (pre-dose) (n=32,11,29,10) | 93.1 % inhibition P-selectin | Standard Deviation 18 |
| Age 12 to <18 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 19 Day 1, 0 hr (pre-dose) (n=36,9,35,10) | 92.4 % inhibition P-selectin | Standard Deviation 12.3 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 35 Day 1, 0 hr (pre-dose) (n=32,11,29,10) | 92.8 % inhibition P-selectin | Standard Deviation 10.3 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 31 Day 1, 0 hr (pre-dose) (n=36,10,32,9) | 89.1 % inhibition P-selectin | Standard Deviation 19.8 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 7 Day 1, 0 hr (pre-dose) (n=41,12,35,12) | 94.6 % inhibition P-selectin | Standard Deviation 11.7 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 23 Day 1, 0 hr (pre-dose) (n=42,11,34,9) | 92.0 % inhibition P-selectin | Standard Deviation 13.5 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 51 Day 1, 0 hr (pre-dose) (n=27,3,26,9) | 95.4 % inhibition P-selectin | Standard Deviation 4.24 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 19 Day 1, 0 hr (pre-dose) (n=36,9,35,10) | 83.5 % inhibition P-selectin | Standard Deviation 34.8 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 15 Day 1, 0 hr (pre-dose) (n=39,9,33,11) | 98.9 % inhibition P-selectin | Standard Deviation 2.9 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 27 Day 1, 0 hr (pre-dose) (n=37,10,33,9) | 91.6 % inhibition P-selectin | Standard Deviation 19.4 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 11 Day 1, 0 hr (pre-dose) (n=41,10,33,10) | 82.3 % inhibition P-selectin | Standard Deviation 30.9 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 43 Day 1, 0 hr (pre-dose) (n=31,3,32,8) | 99.0 % inhibition P-selectin | Standard Deviation 1.67 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 3 Day 1, 0 hr (pre-dose) (n=42,12,36,11) | 97.9 % inhibition P-selectin | Standard Deviation 2.97 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 47 Day 1, 0 hr (pre-dose) (n=28,2,32,9) | 98.8 % inhibition P-selectin | Standard Deviation 1.77 |
| Age 6 to <12 Years, 5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 39 Day 1, 0 hr (pre-dose) (n=33,8,33,11) | 89.7 % inhibition P-selectin | Standard Deviation 23.6 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 7 Day 1, 0 hr (pre-dose) (n=41,12,35,12) | 97.1 % inhibition P-selectin | Standard Deviation 7.36 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 47 Day 1, 0 hr (pre-dose) (n=28,2,32,9) | 95.8 % inhibition P-selectin | Standard Deviation 7.45 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 51 Day 1, 0 hr (pre-dose) (n=27,3,26,9) | 92.5 % inhibition P-selectin | Standard Deviation 19.3 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 3 Day 1, 0 hr (pre-dose) (n=42,12,36,11) | 98.3 % inhibition P-selectin | Standard Deviation 3.74 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 11 Day 1, 0 hr (pre-dose) (n=41,10,33,10) | 97.5 % inhibition P-selectin | Standard Deviation 6.08 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 15 Day 1, 0 hr (pre-dose) (n=39,9,33,11) | 96.8 % inhibition P-selectin | Standard Deviation 8.46 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 19 Day 1, 0 hr (pre-dose) (n=36,9,35,10) | 96.8 % inhibition P-selectin | Standard Deviation 7.36 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 23 Day 1, 0 hr (pre-dose) (n=42,11,34,9) | 94.2 % inhibition P-selectin | Standard Deviation 17.6 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 27 Day 1, 0 hr (pre-dose) (n=37,10,33,9) | 95.4 % inhibition P-selectin | Standard Deviation 10.4 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 31 Day 1, 0 hr (pre-dose) (n=36,10,32,9) | 97.3 % inhibition P-selectin | Standard Deviation 7.02 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 35 Day 1, 0 hr (pre-dose) (n=32,11,29,10) | 92.7 % inhibition P-selectin | Standard Deviation 16.4 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 39 Day 1, 0 hr (pre-dose) (n=33,8,33,11) | 92.7 % inhibition P-selectin | Standard Deviation 18.7 |
| Age 6 to <12 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 43 Day 1, 0 hr (pre-dose) (n=31,3,32,8) | 95.3 % inhibition P-selectin | Standard Deviation 11 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 31 Day 1, 0 hr (pre-dose) (n=36,10,32,9) | 75.5 % inhibition P-selectin | Standard Deviation 37.9 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 15 Day 1, 0 hr (pre-dose) (n=39,9,33,11) | 92.5 % inhibition P-selectin | Standard Deviation 19 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 11 Day 1, 0 hr (pre-dose) (n=41,10,33,10) | 98.3 % inhibition P-selectin | Standard Deviation 2.39 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 51 Day 1, 0 hr (pre-dose) (n=27,3,26,9) | 93.8 % inhibition P-selectin | Standard Deviation 11.8 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 35 Day 1, 0 hr (pre-dose) (n=32,11,29,10) | 70.6 % inhibition P-selectin | Standard Deviation 41 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 7 Day 1, 0 hr (pre-dose) (n=41,12,35,12) | 97.3 % inhibition P-selectin | Standard Deviation 5.92 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 3 Day 1, 0 hr (pre-dose) (n=42,12,36,11) | 97.6 % inhibition P-selectin | Standard Deviation 3.71 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 43 Day 1, 0 hr (pre-dose) (n=31,3,32,8) | 99.1 % inhibition P-selectin | Standard Deviation 2.08 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 39 Day 1, 0 hr (pre-dose) (n=33,8,33,11) | 89.8 % inhibition P-selectin | Standard Deviation 17.9 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 27 Day 1, 0 hr (pre-dose) (n=37,10,33,9) | 87.0 % inhibition P-selectin | Standard Deviation 18.5 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 23 Day 1, 0 hr (pre-dose) (n=42,11,34,9) | 92.2 % inhibition P-selectin | Standard Deviation 15.7 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 19 Day 1, 0 hr (pre-dose) (n=36,9,35,10) | 96.7 % inhibition P-selectin | Standard Deviation 5.51 |
| Age 2 to <6 Years, 8.5 mg/kg | Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B | Week 47 Day 1, 0 hr (pre-dose) (n=28,2,32,9) | 73.1 % inhibition P-selectin | Standard Deviation 42.4 |
Secondary
PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A
Time frame: Week 3, Week 7, Week 11, Week 15, Week 19, Week 23, Week 27, Week 31, Week 35, Week 39, Week 43, Week 47 and Week 51 (Day 1, 0 hr (pre-dose))
Population: Pharmacokinetic analysis set 1 - for treated participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 11 Day 1, 0 hr (pre-dose) (n=9,11,12,11) | 10.2 µg/mL | Standard Deviation 4.92 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 3 Day 1, 0 hr (pre-dose) (n=11,12,13,10) | 16.8 µg/mL | Standard Deviation 4.4 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 7 Day 1, 0 hr (pre-dose) (n=9,12,12,12) | 10.7 µg/mL | Standard Deviation 3.3 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 15 Day 1, 0 hr (pre-dose) (n=7,9,11,12) | 9.42 µg/mL | Standard Deviation 6.47 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 19 Day 1, 0 hr (pre-dose) (n=6,9,12,11) | 6.77 µg/mL | Standard Deviation 4.53 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 23 Day 1, 0 hr (pre-dose) (n=9,12,12,10) | 6.17 µg/mL | Standard Deviation 3.92 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 27 Day 1, 0 hr (pre-dose) (n=9,10,12,10) | 8.05 µg/mL | Standard Deviation 5.32 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 31 Day 1, 0 hr (pre-dose) (n=6,10,11,10) | 9.46 µg/mL | Standard Deviation 4.34 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 35 Day 1, 0 hr (pre-dose) (n=5,11,10,9) | 12.0 µg/mL | Standard Deviation 6.04 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 39 Day 1, 0 hr (pre-dose) (n=7,11,10,11) | 4.93 µg/mL | Standard Deviation 3 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 43 Day 1, 0 hr (pre-dose) (n=8,10,11,8) | 9.23 µg/mL | Standard Deviation 4.73 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 47 Day 1, 0 hr (pre-dose) (n=8,8,10,10) | 7.32 µg/mL | Standard Deviation 3.84 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 51 Day 1, 0 hr (pre-dose) (n=5,9,10,8) | 9.78 µg/mL | Standard Deviation 6.61 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 15 Day 1, 0 hr (pre-dose) (n=7,9,11,12) | 8.45 µg/mL | Standard Deviation 2.93 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 3 Day 1, 0 hr (pre-dose) (n=11,12,13,10) | 14.1 µg/mL | Standard Deviation 5.61 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 7 Day 1, 0 hr (pre-dose) (n=9,12,12,12) | 8.70 µg/mL | Standard Deviation 5.32 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 31 Day 1, 0 hr (pre-dose) (n=6,10,11,10) | 8.57 µg/mL | Standard Deviation 6.17 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 11 Day 1, 0 hr (pre-dose) (n=9,11,12,11) | 6.02 µg/mL | Standard Deviation 4.43 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 51 Day 1, 0 hr (pre-dose) (n=5,9,10,8) | 9.44 µg/mL | Standard Deviation 8.22 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 39 Day 1, 0 hr (pre-dose) (n=7,11,10,11) | 7.04 µg/mL | Standard Deviation 5.75 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 35 Day 1, 0 hr (pre-dose) (n=5,11,10,9) | 6.88 µg/mL | Standard Deviation 3.04 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 23 Day 1, 0 hr (pre-dose) (n=9,12,12,10) | 7.15 µg/mL | Standard Deviation 5.23 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 19 Day 1, 0 hr (pre-dose) (n=6,9,12,11) | 7.75 µg/mL | Standard Deviation 4.92 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 43 Day 1, 0 hr (pre-dose) (n=8,10,11,8) | 7.45 µg/mL | Standard Deviation 5.66 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 47 Day 1, 0 hr (pre-dose) (n=8,8,10,10) | 10.4 µg/mL | Standard Deviation 7.29 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 27 Day 1, 0 hr (pre-dose) (n=9,10,12,10) | 7.70 µg/mL | Standard Deviation 5.93 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 43 Day 1, 0 hr (pre-dose) (n=8,10,11,8) | 18.0 µg/mL | Standard Deviation 8.07 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 15 Day 1, 0 hr (pre-dose) (n=7,9,11,12) | 20.4 µg/mL | Standard Deviation 7.22 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 19 Day 1, 0 hr (pre-dose) (n=6,9,12,11) | 18.8 µg/mL | Standard Deviation 5.28 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 51 Day 1, 0 hr (pre-dose) (n=5,9,10,8) | 12.8 µg/mL | Standard Deviation 10.6 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 23 Day 1, 0 hr (pre-dose) (n=9,12,12,10) | 20.0 µg/mL | Standard Deviation 6.74 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 27 Day 1, 0 hr (pre-dose) (n=9,10,12,10) | 22.4 µg/mL | Standard Deviation 8.71 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 47 Day 1, 0 hr (pre-dose) (n=8,8,10,10) | 14.6 µg/mL | Standard Deviation 8.22 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 31 Day 1, 0 hr (pre-dose) (n=6,10,11,10) | 19.3 µg/mL | Standard Deviation 6.36 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 35 Day 1, 0 hr (pre-dose) (n=5,11,10,9) | 17.9 µg/mL | Standard Deviation 8.03 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 39 Day 1, 0 hr (pre-dose) (n=7,11,10,11) | 19.9 µg/mL | Standard Deviation 5.21 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 3 Day 1, 0 hr (pre-dose) (n=11,12,13,10) | 30.1 µg/mL | Standard Deviation 6.17 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 7 Day 1, 0 hr (pre-dose) (n=9,12,12,12) | 22.1 µg/mL | Standard Deviation 8.09 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 11 Day 1, 0 hr (pre-dose) (n=9,11,12,11) | 20.1 µg/mL | Standard Deviation 9.36 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 39 Day 1, 0 hr (pre-dose) (n=7,11,10,11) | 12.8 µg/mL | Standard Deviation 7.98 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 31 Day 1, 0 hr (pre-dose) (n=6,10,11,10) | 9.68 µg/mL | Standard Deviation 8.29 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 27 Day 1, 0 hr (pre-dose) (n=9,10,12,10) | 11.8 µg/mL | Standard Deviation 9.3 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 15 Day 1, 0 hr (pre-dose) (n=7,9,11,12) | 10.3 µg/mL | Standard Deviation 5.84 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 3 Day 1, 0 hr (pre-dose) (n=11,12,13,10) | 19.8 µg/mL | Standard Deviation 5.62 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 23 Day 1, 0 hr (pre-dose) (n=9,12,12,10) | 10.6 µg/mL | Standard Deviation 5.24 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 19 Day 1, 0 hr (pre-dose) (n=6,9,12,11) | 10.2 µg/mL | Standard Deviation 5.93 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 11 Day 1, 0 hr (pre-dose) (n=9,11,12,11) | 11.0 µg/mL | Standard Deviation 3.8 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 7 Day 1, 0 hr (pre-dose) (n=9,12,12,12) | 13.4 µg/mL | Standard Deviation 3.21 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 35 Day 1, 0 hr (pre-dose) (n=5,11,10,9) | 8.43 µg/mL | Standard Deviation 6.78 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 51 Day 1, 0 hr (pre-dose) (n=5,9,10,8) | 10.3 µg/mL | Standard Deviation 3.21 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 47 Day 1, 0 hr (pre-dose) (n=8,8,10,10) | 10.5 µg/mL | Standard Deviation 9.26 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A | Week 43 Day 1, 0 hr (pre-dose) (n=8,10,11,8) | 12.8 µg/mL | Standard Deviation 4.95 |
Secondary
PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B
Time frame: Week 3, Week 7, Week 11, Week 15, Week 19, Week 23, Week 27, Week 31, Week 35, Week 39, Week 43, Week 47 and Week 51 (0 hr (pre-dose))
Population: Pharmacokinetic analysis set 2 - for treated participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 27 Day 1, 0 hr (pre-dose) (n=40,10,34,10) | 7.07 µg/mL | Standard Deviation 4.26 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 31 Day 1, 0 hr (pre-dose) (n=39,10,35,10) | 7.30 µg/mL | Standard Deviation 4.8 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 51 Day 1, 0 hr (pre-dose) | 8.48 µg/mL | Standard Deviation 5.48 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 39 Day 1, 0 hr (pre-dose) (n=38,11,35,12) | 7.69 µg/mL | Standard Deviation 5.46 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 35 Day 1, 0 hr (pre-dose) (n=35,11,32,10) | 8.96 µg/mL | Standard Deviation 4.94 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 11 Day 1, 0 hr (pre-dose)(n=45,11,33,11) | 9.18 µg/mL | Standard Deviation 5.57 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 3 Day 1, 0 hr (pre-dose) (n=45,12,36,11) | 16.6 µg/mL | Standard Deviation 4.4 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 47 Day 1, 0 hr (pre-dose) | 8.99 µg/mL | Standard Deviation 5.76 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 15 Day 1, 0 hr (pre-dose) (n=39,9,33,12) | 8.65 µg/mL | Standard Deviation 5.73 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 19 Day 1, 0 hr (pre-dose) (n=38,9,35,11) | 8.13 µg/mL | Standard Deviation 5.65 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 7 Day 1, 0 hr (pre-dose) (n=44,12,35,13) | 10.3 µg/mL | Standard Deviation 5.49 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 43 Day 1, 0 hr (pre-dose) (n=35,10,34,9) | 8.68 µg/mL | Standard Deviation 4.5 |
| Age 12 to <18 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 23 Day 1, 0 hr (pre-dose) (n=43,12,35,10) | 7.09 µg/mL | Standard Deviation 4.45 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 27 Day 1, 0 hr (pre-dose) (n=40,10,34,10) | 7.70 µg/mL | Standard Deviation 5.93 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 3 Day 1, 0 hr (pre-dose) (n=45,12,36,11) | 14.1 µg/mL | Standard Deviation 5.61 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 39 Day 1, 0 hr (pre-dose) (n=38,11,35,12) | 7.04 µg/mL | Standard Deviation 5.75 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 15 Day 1, 0 hr (pre-dose) (n=39,9,33,12) | 8.45 µg/mL | Standard Deviation 2.93 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 31 Day 1, 0 hr (pre-dose) (n=39,10,35,10) | 8.57 µg/mL | Standard Deviation 6.17 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 51 Day 1, 0 hr (pre-dose) | 9.44 µg/mL | Standard Deviation 8.22 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 43 Day 1, 0 hr (pre-dose) (n=35,10,34,9) | 7.45 µg/mL | Standard Deviation 5.66 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 23 Day 1, 0 hr (pre-dose) (n=43,12,35,10) | 7.15 µg/mL | Standard Deviation 5.23 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 35 Day 1, 0 hr (pre-dose) (n=35,11,32,10) | 6.88 µg/mL | Standard Deviation 3.04 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 19 Day 1, 0 hr (pre-dose) (n=38,9,35,11) | 7.75 µg/mL | Standard Deviation 4.92 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 11 Day 1, 0 hr (pre-dose)(n=45,11,33,11) | 6.02 µg/mL | Standard Deviation 4.43 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 7 Day 1, 0 hr (pre-dose) (n=44,12,35,13) | 8.70 µg/mL | Standard Deviation 5.32 |
| Age 6 to <12 Years, 5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 47 Day 1, 0 hr (pre-dose) | 10.4 µg/mL | Standard Deviation 7.29 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 39 Day 1, 0 hr (pre-dose) (n=38,11,35,12) | 14.2 µg/mL | Standard Deviation 7.79 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 3 Day 1, 0 hr (pre-dose) (n=45,12,36,11) | 23.6 µg/mL | Standard Deviation 7.54 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 7 Day 1, 0 hr (pre-dose) (n=44,12,35,13) | 16.3 µg/mL | Standard Deviation 7.5 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 11 Day 1, 0 hr (pre-dose)(n=45,11,33,11) | 15.3 µg/mL | Standard Deviation 7.78 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 15 Day 1, 0 hr (pre-dose) (n=39,9,33,12) | 16.7 µg/mL | Standard Deviation 7.34 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 19 Day 1, 0 hr (pre-dose) (n=38,9,35,11) | 17.5 µg/mL | Standard Deviation 5.93 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 23 Day 1, 0 hr (pre-dose) (n=43,12,35,10) | 16.6 µg/mL | Standard Deviation 6.9 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 27 Day 1, 0 hr (pre-dose) (n=40,10,34,10) | 16.5 µg/mL | Standard Deviation 8.45 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 31 Day 1, 0 hr (pre-dose) (n=39,10,35,10) | 16.1 µg/mL | Standard Deviation 7.57 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 35 Day 1, 0 hr (pre-dose) (n=35,11,32,10) | 13.6 µg/mL | Standard Deviation 7.75 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 43 Day 1, 0 hr (pre-dose) (n=35,10,34,9) | 14.8 µg/mL | Standard Deviation 6.94 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 47 Day 1, 0 hr (pre-dose) | 13.8 µg/mL | Standard Deviation 6.8 |
| Age 6 to <12 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 51 Day 1, 0 hr (pre-dose) | 13.4 µg/mL | Standard Deviation 7.9 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 23 Day 1, 0 hr (pre-dose) (n=43,12,35,10) | 10.6 µg/mL | Standard Deviation 5.24 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 39 Day 1, 0 hr (pre-dose) (n=38,11,35,12) | 13.4 µg/mL | Standard Deviation 7.89 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 19 Day 1, 0 hr (pre-dose) (n=38,9,35,11) | 10.2 µg/mL | Standard Deviation 5.93 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 15 Day 1, 0 hr (pre-dose) (n=39,9,33,12) | 10.3 µg/mL | Standard Deviation 5.84 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 3 Day 1, 0 hr (pre-dose) (n=45,12,36,11) | 20.0 µg/mL | Standard Deviation 5.37 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 43 Day 1, 0 hr (pre-dose) (n=35,10,34,9) | 13.6 µg/mL | Standard Deviation 5.15 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 11 Day 1, 0 hr (pre-dose)(n=45,11,33,11) | 11.0 µg/mL | Standard Deviation 3.8 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 51 Day 1, 0 hr (pre-dose) | 11.6 µg/mL | Standard Deviation 4.9 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 47 Day 1, 0 hr (pre-dose) | 10.5 µg/mL | Standard Deviation 9.26 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 7 Day 1, 0 hr (pre-dose) (n=44,12,35,13) | 14.4 µg/mL | Standard Deviation 4.57 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 35 Day 1, 0 hr (pre-dose) (n=35,11,32,10) | 10.0 µg/mL | Standard Deviation 8.11 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 31 Day 1, 0 hr (pre-dose) (n=39,10,35,10) | 9.68 µg/mL | Standard Deviation 8.29 |
| Age 2 to <6 Years, 8.5 mg/kg | PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B | Week 27 Day 1, 0 hr (pre-dose) (n=40,10,34,10) | 11.8 µg/mL | Standard Deviation 9.3 |