A Phase 2 interventional study of Crizanlizumab in Sickle Cell Disease (SCD), sponsored by Novartis Pharmaceuticals. Completed at 35 sites in 14 countries. Open to participants aged 2 Years to 17 Years. Per ClinicalTrials.gov, last updated 2025-10-16.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 2, Interventional, and Treatment
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Among 10 studies testing crizanlizumab in Anemia, Sickle Cell — 3 open to participants now, 4 under way, 2 of them phase 3. crizanlizumab · Anemia, Sickle Cell.
Among the 10 studies testing crizanlizumab in Anemia, Sickle Cell, this one is the 6th largest by enrollment, is the only one that started in 2018, is one of 5 in phase 2, and was the 3rd registered.
1,134 studies on the registry are indexed under Anemia, Sickle Cell; 238 are open to participants now.
Browse Anemia, Sickle Cell studies →3 of the 10 studies testing crizanlizumab in Anemia, Sickle Cell are open now, in 12 countries. Recruiting first, the newest first:
Novartis Pharmaceuticals · Sites in United States, Brazil, Colombia and 2 more countries
Ages 12–100
Novartis Pharmaceuticals · Sites in United States, Belgium, Brazil and 8 more countries
Ages 6 mo–100 yrs
Children's Hospital Los Angeles
Ages 16+
By country, each count listing its studies:
crizanlizumab: first FDA approval 2019 (ADAKVEO), first EMA approval 2020. What it is approved for, and how studies give it, is on its page →
Of the 177 Anemia, Sickle Cell studies recruiting now, 64 (36%) set no upper age limit and 97 (55%) stop at 75 or younger; 127 take children under 18; 29 take healthy volunteers.
This study: 2 Years to 17 Years · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
10 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 1 · Phase 2 6 · Phase 3 2 · Phase 4 2
First in 2013; this study’s year is marked. 1 started in 2018.
This study's enrollment of 117 is above the median of 40 across 769 interventional studies indexed under Anemia, Sickle Cell.
Median enrollment 124 across the 10 interventional studies. Of the 6 that completed or were terminated, 6 (100%) have results posted.
This tab as a report to print or save as PDF → With an account.
9 of 10 have an industry lead sponsor. The 3 most frequent:
This study is registered under Novartis Pharmaceuticals, one of the names counted as Novartis. Under that name alone:
Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
25 studies in Anemia, Sickle Cell by Novartis: 3 open now, 5 under way, 2 of them phase 3. Of 19 finished, 9 (47%) have results posted.
Among the 25 studies in Anemia, Sickle Cell by Novartis, this one is the 10th largest by enrollment of the 16 interventional ones that give a count, is the only one that started in 2018, is one of 8 in phase 2, and was the 9th registered.
Novartis’s Anemia, Sickle Cell studies by the year they started, since 2003.
None of the studies under way reaches primary completion within a year.
Among the 10 studies testing crizanlizumab in Anemia, Sickle Cell, from their registry updates:
Nothing recorded among them since 2026-09-25.
Among Novartis’s 25 in Anemia, Sickle Cell:
Nothing recorded among them since 2026-09-25.
This tab as a report to print or save as PDF → With an account.
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.
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:
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
6. or to any drug from similar class as study drug or to any 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 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 (HIV) infection (detectable viral load).
18.Patients with known active infection. 19.Patients with known history. 20.Significant active infection or immune deficiency (including chronic use of drugs) in the opinion of the investigator.
21.Malignant disease. Exceptions to this exclusion include the following: 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 ≥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. 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 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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The protein in red blood cells that carries oxygen. A low level is anemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorized to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colors or preservatives.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorized to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colors or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
SEG101 (crizanlizumab) 5 mg/kg or 8 mg/kg i.v. administered on Week 1 Day 1, Week3 Day 1 and Day 1 of every 4-week cycle 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.
Drug: Crizanlizumab
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.
Also known as: SEG101
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
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
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)
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
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
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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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))
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))
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))
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))
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.
| Milestone | 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 |
|---|---|---|---|---|
| Started | 50 | 13 | 40 | 14 |
| Completed | 33 | 10 | 29 | 11 |
| Not completed | 17 | 3 | 11 | 3 |
| Withdrew: Pregnancy | 1 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 | 0 |
| Withdrew: Death | 1 | 0 | 0 | 0 |
| Withdrew: Adverse event | 1 | 0 | 0 | 1 |
| Withdrew: Physician decision | 3 | 1 | 2 | 0 |
| Withdrew: Participant decision | 7 | 0 | 1 | 0 |
| Withdrew: Guardian decision | 4 | 2 | 7 | 2 |
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.
| hr*ug/mL | 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 |
|---|---|---|---|---|
| Pharmacokinetics (PK): AUCd15 of Crizanlizumab After First Dose - Part A | 10500 ± 2290 | 8180 ± 1620 | 20600 ± 4530 | 14400 ± 3990 |
The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).
| hr*ug/mL | 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 |
|---|---|---|---|---|
| Pharmacokinetics (PK) - AUCtau for Serum Crizanlizumab After Multiple Doses - Part A - Steady State | 15800 ± 2080 | 14800 ± 3770 | 35700 ± 8100 | 22100 ± 6200 |
The maximum (peak) observed, serum, drug concentration after single or multiple dose administration (mass x volume-1)
| ug/mL | 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 |
|---|---|---|---|---|
| PK Single Dose (Week 1) (n=11,11,13,10) | 80.5 ± 17.7 | 65.9 ± 11.3 | 175 ± 36.0 | 110 ± 37.3 |
| PK Multiple Dose - Week 15 (Steady state) (n=7,8,12,12) | 95.6 ± 26.6 | 77.5 ± 19.0 | 171 ± 35.3 | 111 ± 27.4 |
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.
| hr*{Percent} inhibition P-selectin | 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 |
|---|---|---|---|---|
| Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab After First Dose - Part A - AUCd15 | 33700 ± 2440 | 34400 ± 3660 | 33200 ± 3410 | — |
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.
| hr*{Percent} inhibition P-selectin | 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 |
|---|---|---|---|---|
| Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab - Part A - AUCtau After Multiple Dose - Steady State | 66700 ± 9560 | 64800 ± 3550 | 68600 ± 9210 | 66300 ± 5710 |
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
| Participants | 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 |
|---|---|---|---|---|
| Adverse events (AEs) | 47 | 13 | 38 | 14 |
| AEs -Treatment-related | 16 | 5 | 14 | 4 |
| Serious Adverse events (SAEs) | 18 | 9 | 20 | 12 |
| SAEs -Treatment-related | 1 | 1 | 2 | 1 |
| Fatal SAEs | 1 | 0 | 0 | 0 |
| Fatal SAEs-Treatment-related | 0 | 0 | 0 | 0 |
| AEs leading to dose interruption/reduction | 17 | 6 | 10 | 7 |
| AEs requiring additional therapy | 45 | 13 | 37 | 14 |
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)
| VOC events per year | 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 |
|---|---|---|---|---|
| Baseline annualized rate of VOC | 3.00 (1.0 to 26.0) | 1.00 (0.0 to 6.0) | 2.00 (1.0 to 13.0) | 1.00 (1.0 to 5.0) |
| Annualized rate of VOC on treatment (up to Year 2) | 1.80 (0.0 to 14.5) | 0.79 (0.0 to 10.4) | 1.48 (0.0 to 8.7) | 1.22 (0.0 to 5.3) |
| Annualized rate of VOC on treatment Year 1 (n=42,11,35,12) | 2.00 (0.0 to 14.0) | 0.00 (0.0 to 4.0) | 1.00 (0.0 to 6.0) | 0.00 (0.0 to 3.0) |
| Annualized rate of VOC on treatment Year 2 (n=32,10,27,10) | 2.00 (0.0 to 8.0) | 0.00 (0.0 to 5.0) | 1.00 (0.0 to 9.0) | 2.00 (0.0 to 4.0) |
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)
| VOC events per year | 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 |
|---|---|---|---|---|
| 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 (0.5 to 3.9) | 2.71 (0.5 to 4.9) | 0.49 (0.49 to 3.0) | 0.73 (0.5 to 1.0) |
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.
| VOC events per year | 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 |
|---|---|---|---|---|
| Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Uncomplicated Pain Crisis | 1.79 (0.0 to 14.5) | 0.98 (0.0 to 10.4) | 1.47 (0.0 to 8.7) | 0.97 (0.0 to 5.3) |
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).
| VOC events per year | 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 |
|---|---|---|---|---|
| Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Acute Chest Syndrome | 0.49 (0.0 to 3.7) | 0.64 (0.0 to 1.5) | 0.49 (0.0 to 1.0) | 0.49 (0.0 to 1.9) |
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.
No measurements were reported for this outcome.
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.
| VOC events per year | 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 |
|---|---|---|---|---|
| Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Splenic Sequestration | 0.00 (0.0 to 0.5) | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) | — |
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.
| VOC events per year | 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 |
|---|---|---|---|---|
| Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Priapism | — | 0.49 (0.49 to 0.49) | 0.00 (0.0 to 0.0) | — |
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)
| hospitalizations and ER visits per year | 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 |
|---|---|---|---|---|
| Annualized rate of hospitalizations and ER visits (up to Year 2) | 1.78 (0.0 to 13.5) | 0.50 (0.0 to 10.4) | 1.01 (0.0 to 9.6) | 0.74 (0.0 to 5.3) |
| Annualized rate of hospitalizations and ER visits Year 1 (n=42,11,35,12) | 2.00 (0.0 to 14.0) | 0.00 (0.0 to 5.0) | 1.00 (0.0 to 6.0) | 0.00 (0.0 to 3.0) |
| Annualized rate of hospitalizations and ER visits Year 2 (n=32,10,27,10) | 2.00 (0.0 to 9.0) | 0.00 (0.0 to 5.0) | 1.00 (0.0 to 10.0) | 1.00 (0.0 to 3.0) |
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)
| hospitalizations and ER visits per year | 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 |
|---|---|---|---|---|
| Annualized rate of hospitalizations and ER visits (up to Year 2) | 2.68 (0.0 to 15.5) | 1.46 (0.0 to 11.4) | 1.59 (0.0 to 11.7) | 1.74 (0.0 to 7.7) |
| Annualized rate of hospitalizations and ER visits Year 1 (n=42,11,35,12) | 2.00 (0.0 to 16.0) | 1.00 (0.0 to 5.0) | 2.00 (0.0 to 7.0) | 2.00 (0.0 to 8.0) |
| Annualized rate of hospitalizations and ER visits Year 2 (n=32,10,27,10) | 2.50 (0.0 to 10.0) | 1.00 (0.0 to 8.0) | 1.00 (0.0 to 10.0) | 2.00 (0.0 to 4.0) |
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)
| Days per year | 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 |
|---|---|---|---|---|
| Annualized days of ER/Hospitalization on treatment - VOC related (up to Year 2) | 6.74 (0.0 to 87.0) | 0.98 (0.0 to 59.2) | 5.36 (0.0 to 40.0) | 2.20 (0.0 to 42.7) |
| Annualized days of ER/Hospitalization on treatment - Total (up to Year 2) | 12.37 (0.0 to 87.0) | 5.41 (0.0 to 59.2) | 9.03 (0.0 to 57.5) | 10.48 (0.0 to 42.7) |
| Annualized days of ER/Hospitalization Year 1 - VOC related (n=42,11,12, 12) | 7.00 (0.0 to 60.3) | 0.00 (0.0 to 23.0) | 5.00 (0.0 to 37.0) | 0.00 (0.0 to 29.0) |
| Annualized days of ER/Hospitalization Year 1 - Total (n=42,11,12, 12) | 7.00 (0.0 to 60.3) | 2.00 (0.0 to 24.0) | 11.00 (0.0 to 37.0) | 6.50 (0.0 to 34.0) |
| Annualized days of ER/Hospitalization Year 2 - VOC related (n=32,10,11, 10) | 10.50 (0.0 to 71.0) | 0.00 (0.0 to 48.0) | 2.00 (0.0 to 40.0) | 3.00 (0.0 to 19.0) |
| Annualized days of ER/Hospitalization Year 2 - Total (n=32,10,11, 10) | 13.00 (0.0 to 71.0) | 2.00 (0.0 to 64.0) | 3.00 (0.0 to 40.0) | 10.50 (0.0 to 37.0) |
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.
No measurements were reported for this outcome.
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.
| g/L | 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 |
|---|---|---|---|---|
| Week 27 | -1.26 ± 11.472 | 2.33 ± 6.856 | -0.33 ± 7.015 | 1.55 ± 9.905 |
| End Of Treatment / Year 2 (n=24,6,11,2) | -5.38 ± 11.088 | 2.33 ± 7.941 | -1.18 ± 11.677 | 15.00 ± 1.414 |
Anti-drug antibodies (ADA) are antibodies elicited from therapeutics and they are used to measure immunogenicity.
| Participants | 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 |
|---|---|---|---|---|
| Baseline - Negative | 50 | 13 | 39 | 14 |
| Baseline - Positive | 0 | 0 | 0 | 0 |
| Baseline - Missing | 0 | 0 | 1 | 0 |
| Post-baseline - Any positive | 0 | 1 | 1 | 0 |
| Post-baseline - only last sample positive | 0 | 0 | 0 | 0 |
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
| Participants | 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 |
|---|---|---|---|---|
| QTcF (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 1 | 1 | 2 | 1 |
| QTcF (ms)- Increase >60 ms (n=49,13,37,12) | 0 | 0 | 0 | 0 |
| QTcF (ms)- New >450 to <=480 ms (n=49,13,40,13) | 3 | 0 | 0 | 0 |
| QTcF (ms)- New >480 to <=500 ms (n=49,13,40,13) | 0 | 0 | 1 | 0 |
| QTcF (ms)-New >500 ms (n=49,13,40,13) | 0 | 0 | 0 | 0 |
| QTcB (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 12 | 3 | 7 | 1 |
| QTcB (ms)-Increase >60 ms (n=49,13,37,12) | 0 | 0 | 0 | 0 |
| QTcB (ms)-New >450 to <=480 ms (n=40,12,35,13) | 10 | 2 | 14 | 6 |
| QTcB (ms)-New >480 to <=500 ms (n=49,13,40,13) | 3 | 0 | 1 | 0 |
| QTcB (ms)-New >500 ms (n=49,13,40,13) | 0 | 0 | 0 | 0 |
| QT (ms)-Increase >30 to <=60 ms (n=49,13,37,12) | 13 | 5 | 17 | 3 |
| QT (ms)-Increase >60 ms (n=49,13,37,12) | 2 | 0 | 2 | 0 |
| QT (ms)-New >450 to <=480 ms (n=49,13,40,13) | 0 | 0 | 0 | 0 |
| QT (ms)-New >480 to <=500 ms (n=49,13,40,13) | 0 | 0 | 0 | 0 |
| QT (ms)-New >500 ms (n=49,13,40,13) | 0 | 0 | 0 | 0 |
| PR (ms)-Increase >25% and PR >200 ms (n=48,13,37,12) | 0 | 0 | 0 | 0 |
| PR (ms)-New PR >200 ms (n=48,13,40,13) | 2 | 0 | 0 | 0 |
| QRS (ms)- Increase >25% and QRS >120 ms (n=49,13,37,12) | 0 | 0 | 0 | 0 |
| QRS (ms)-New QRS >120 ms (n=49,13,40,13) | 0 | 0 | 0 | 0 |
| RR (ms)-Increase >25% and RR >1200 ms (n=49,13,37,12) | 1 | 0 | 0 | 0 |
| RR (ms)-Decrease >25% and RR <600 ms (n=49,12,34,7) | 0 | 1 | 2 | 0 |
| HR (bpm)-Increase >25% and HR >100 bpm (n=49,12,34,7) | 1 | 1 | 3 | 0 |
| HR (bpm)-Decrease >25% and HR <50 bpm (n=49,13,37,12) | 0 | 0 | 0 | 0 |
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.
| Participants | 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 |
|---|---|---|---|---|
| Delayed puberty = yes | — | 0 | 0 | 0 |
| Delayed puberty = no | — | 0 | 0 | 0 |
| Delayed puberty = unknown (i.e., not applicable because pt not yet in age range for puberty) | — | 3 | 12 | 5 |
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.
| Participants | 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 |
|---|---|---|---|---|
| Delayed puberty = yes | 0 | 0 | 0 | 0 |
| Delayed puberty = no | 4 | 0 | 0 | 0 |
| Delayed puberty = unknown (i.e., not applicable because pt not yet in age range for puberty) | 0 | 7 | 18 | 9 |
| µg/mL | 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 |
|---|---|---|---|---|
| Week 3 Day 1, 0 hr (pre-dose) (n=11,12,13,10) | 16.8 ± 4.40 | 14.1 ± 5.61 | 30.1 ± 6.17 | 19.8 ± 5.62 |
| Week 7 Day 1, 0 hr (pre-dose) (n=9,12,12,12) | 10.7 ± 3.30 | 8.70 ± 5.32 | 22.1 ± 8.09 | 13.4 ± 3.21 |
| Week 11 Day 1, 0 hr (pre-dose) (n=9,11,12,11) | 10.2 ± 4.92 | 6.02 ± 4.43 | 20.1 ± 9.36 | 11.0 ± 3.80 |
| Week 15 Day 1, 0 hr (pre-dose) (n=7,9,11,12) | 9.42 ± 6.47 | 8.45 ± 2.93 | 20.4 ± 7.22 | 10.3 ± 5.84 |
| Week 19 Day 1, 0 hr (pre-dose) (n=6,9,12,11) | 6.77 ± 4.53 | 7.75 ± 4.92 | 18.8 ± 5.28 | 10.2 ± 5.93 |
| Week 23 Day 1, 0 hr (pre-dose) (n=9,12,12,10) | 6.17 ± 3.92 | 7.15 ± 5.23 | 20.0 ± 6.74 | 10.6 ± 5.24 |
| Week 27 Day 1, 0 hr (pre-dose) (n=9,10,12,10) | 8.05 ± 5.32 | 7.70 ± 5.93 | 22.4 ± 8.71 | 11.8 ± 9.30 |
| Week 31 Day 1, 0 hr (pre-dose) (n=6,10,11,10) | 9.46 ± 4.34 | 8.57 ± 6.17 | 19.3 ± 6.36 | 9.68 ± 8.29 |
| Week 35 Day 1, 0 hr (pre-dose) (n=5,11,10,9) | 12.0 ± 6.04 | 6.88 ± 3.04 | 17.9 ± 8.03 | 8.43 ± 6.78 |
| Week 39 Day 1, 0 hr (pre-dose) (n=7,11,10,11) | 4.93 ± 3.00 | 7.04 ± 5.75 | 19.9 ± 5.21 | 12.8 ± 7.98 |
| Week 43 Day 1, 0 hr (pre-dose) (n=8,10,11,8) | 9.23 ± 4.73 | 7.45 ± 5.66 | 18.0 ± 8.07 | 12.8 ± 4.95 |
| Week 47 Day 1, 0 hr (pre-dose) (n=8,8,10,10) | 7.32 ± 3.84 | 10.4 ± 7.29 | 14.6 ± 8.22 | 10.5 ± 9.26 |
| Week 51 Day 1, 0 hr (pre-dose) (n=5,9,10,8) | 9.78 ± 6.61 | 9.44 ± 8.22 | 12.8 ± 10.6 | 10.3 ± 3.21 |
| µg/mL | 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 |
|---|---|---|---|---|
| Week 3 Day 1, 0 hr (pre-dose) (n=45,12,36,11) | 16.6 ± 4.40 | 14.1 ± 5.61 | 23.6 ± 7.54 | 20.0 ± 5.37 |
| Week 7 Day 1, 0 hr (pre-dose) (n=44,12,35,13) | 10.3 ± 5.49 | 8.70 ± 5.32 | 16.3 ± 7.50 | 14.4 ± 4.57 |
| Week 11 Day 1, 0 hr (pre-dose)(n=45,11,33,11) | 9.18 ± 5.57 | 6.02 ± 4.43 | 15.3 ± 7.78 | 11.0 ± 3.80 |
| Week 15 Day 1, 0 hr (pre-dose) (n=39,9,33,12) | 8.65 ± 5.73 | 8.45 ± 2.93 | 16.7 ± 7.34 | 10.3 ± 5.84 |
| Week 19 Day 1, 0 hr (pre-dose) (n=38,9,35,11) | 8.13 ± 5.65 | 7.75 ± 4.92 | 17.5 ± 5.93 | 10.2 ± 5.93 |
| Week 23 Day 1, 0 hr (pre-dose) (n=43,12,35,10) | 7.09 ± 4.45 | 7.15 ± 5.23 | 16.6 ± 6.90 | 10.6 ± 5.24 |
| Week 27 Day 1, 0 hr (pre-dose) (n=40,10,34,10) | 7.07 ± 4.26 | 7.70 ± 5.93 | 16.5 ± 8.45 | 11.8 ± 9.30 |
| Week 31 Day 1, 0 hr (pre-dose) (n=39,10,35,10) | 7.30 ± 4.80 | 8.57 ± 6.17 | 16.1 ± 7.57 | 9.68 ± 8.29 |
| Week 35 Day 1, 0 hr (pre-dose) (n=35,11,32,10) | 8.96 ± 4.94 | 6.88 ± 3.04 | 13.6 ± 7.75 | 10.0 ± 8.11 |
| Week 39 Day 1, 0 hr (pre-dose) (n=38,11,35,12) | 7.69 ± 5.46 | 7.04 ± 5.75 | 14.2 ± 7.79 | 13.4 ± 7.89 |
| Week 43 Day 1, 0 hr (pre-dose) (n=35,10,34,9) | 8.68 ± 4.50 | 7.45 ± 5.66 | 14.8 ± 6.94 | 13.6 ± 5.15 |
| Week 47 Day 1, 0 hr (pre-dose) | 8.99 ± 5.76 | 10.4 ± 7.29 | 13.8 ± 6.80 | 10.5 ± 9.26 |
| Week 51 Day 1, 0 hr (pre-dose) | 8.48 ± 5.48 | 9.44 ± 8.22 | 13.4 ± 7.90 | 11.6 ± 4.90 |
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.
| % inhibition P-selectin | 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 |
|---|---|---|---|---|
| Week 3 Day 1, 0 hr (pre-dose) (n=11,12,13,9) | 100 ± 0.0924 | 97.9 ± 2.97 | 99.1 ± 1.41 | 98.6 ± 2.54 |
| Week 7 Day 1, 0 hr (pre-dose) (n=9,11,12,10) | 99.0 ± 1.61 | 94.2 ± 12.2 | 98.5 ± 3.48 | 98.9 ± 1.91 |
| Week 11 Day 1, 0 hr (pre-dose) (n=9,9,12,9) | 97.7 ± 4.56 | 80.8 ± 32.4 | 98.5 ± 2.93 | 98.4 ± 2.50 |
| Week 15 Day 1, 0 hr (pre-dose) (n=6,8,11,10) | 96.6 ± 8.04 | 99.8 ± 0.422 | 99.2 ± 1.86 | 91.7 ± 19.8 |
| Week 19 Day 1, 0 hr (pre-dose) (n=6,9,12,10) | 88.6 ± 20.6 | 83.5 ± 34.8 | 99.2 ± 1.54 | 96.7 ± 5.51 |
| Week 23 Day 1, 0 hr (pre-dose) (n=9,10,11,9) | 83.8 ± 28.9 | 91.2 ± 14.0 | 99.5 ± 1.24 | 92.2 ± 15.7 |
| Week 27 Day 1, 0 hr (pre-dose) (n=9,9,11,8) | 88.0 ± 25.0 | 90.8 ± 20.4 | 99.4 ± 1.36 | 85.4 ± 19.1 |
| Week 31 Day 1, 0 hr (pre-dose) (n=6,9,9,9) | 97.8 ± 2.83 | 88.9 ± 21.0 | 99.6 ± 1.30 | 75.5 ± 37.9 |
| Week 35 Day 1, 0 hr (pre-dose) (n=5,10,8,9) | 97.2 ± 6.04 | 92.3 ± 10.6 | 97.9 ± 3.81 | 67.4 ± 42.1 |
| Week 39 Day 1, 0 hr (pre-dose) (n=7,7,8,9) | 80.8 ± 28.0 | 88.6 ± 25.3 | 99.1 ± 2.01 | 87.6 ± 19.2 |
| Week 43 Day 1, 0 hr (pre-dose) (n=8,3,9,6) | 96.7 ± 4.19 | 99.0 ± 1.67 | 98.8 ± 2.14 | 98.8 ± 2.37 |
| Week 47 Day 1, 0 hr (pre-dose) (n=8,2,8,8) | 87.1 ± 30.5 | 98.8 ± 1.77 | 98.1 ± 3.73 | 69.8 ± 44.0 |
| Week 51 Day 1, 0 hr (pre-dose) (n=5,3,8,7) | 80.9 ± 34.0 | 95.4 ± 4.24 | 98.9 ± 1.86 | 92.1 ± 13.0 |
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.
| % inhibition P-selectin | 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 |
|---|---|---|---|---|
| Week 3 Day 1, 0 hr (pre-dose) (n=42,12,36,11) | 99.3 ± 2.14 | 97.9 ± 2.97 | 98.3 ± 3.74 | 97.6 ± 3.71 |
| Week 7 Day 1, 0 hr (pre-dose) (n=41,12,35,12) | 93.7 ± 17.0 | 94.6 ± 11.7 | 97.1 ± 7.36 | 97.3 ± 5.92 |
| Week 11 Day 1, 0 hr (pre-dose) (n=41,10,33,10) | 92.7 ± 17.8 | 82.3 ± 30.9 | 97.5 ± 6.08 | 98.3 ± 2.39 |
| Week 15 Day 1, 0 hr (pre-dose) (n=39,9,33,11) | 92.6 ± 18.9 | 98.9 ± 2.90 | 96.8 ± 8.46 | 92.5 ± 19.0 |
| Week 19 Day 1, 0 hr (pre-dose) (n=36,9,35,10) | 92.4 ± 12.3 | 83.5 ± 34.8 | 96.8 ± 7.36 | 96.7 ± 5.51 |
| Week 23 Day 1, 0 hr (pre-dose) (n=42,11,34,9) | 86.5 ± 26.3 | 92.0 ± 13.5 | 94.2 ± 17.6 | 92.2 ± 15.7 |
| Week 27 Day 1, 0 hr (pre-dose) (n=37,10,33,9) | 87.6 ± 26.1 | 91.6 ± 19.4 | 95.4 ± 10.4 | 87.0 ± 18.5 |
| Week 31 Day 1, 0 hr (pre-dose) (n=36,10,32,9) | 90.9 ± 18.7 | 89.1 ± 19.8 | 97.3 ± 7.02 | 75.5 ± 37.9 |
| Week 35 Day 1, 0 hr (pre-dose) (n=32,11,29,10) | 93.1 ± 18.0 | 92.8 ± 10.3 | 92.7 ± 16.4 | 70.6 ± 41.0 |
| Week 39 Day 1, 0 hr (pre-dose) (n=33,8,33,11) | 85.4 ± 23.6 | 89.7 ± 23.6 | 92.7 ± 18.7 | 89.8 ± 17.9 |
| Week 43 Day 1, 0 hr (pre-dose) (n=31,3,32,8) | 93.1 ± 15.4 | 99.0 ± 1.67 | 95.3 ± 11.0 | 99.1 ± 2.08 |
| Week 47 Day 1, 0 hr (pre-dose) (n=28,2,32,9) | 91.7 ± 17.7 | 98.8 ± 1.77 | 95.8 ± 7.45 | 73.1 ± 42.4 |
| Week 51 Day 1, 0 hr (pre-dose) (n=27,3,26,9) | 86.4 ± 25.8 | 95.4 ± 4.24 | 92.5 ± 19.3 | 93.8 ± 11.8 |
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
| Participants | 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 |
|---|---|---|---|---|
| Number of participants with at least one event | 16 | 5 | 14 | 4 |
| Infusion related reaction | 5 | 2 | 3 | 1 |
| Back pain | 3 | 0 | 4 | 2 |
| Nausea | 3 | 0 | 1 | 0 |
| Pain in extremity | 2 | 0 | 2 | 0 |
| Sickle cell anaemia with crisis | 0 | 0 | 2 | 1 |
| Arthralgia | 0 | 1 | 1 | 0 |
| Conjunctivitis | 1 | 1 | 0 | 0 |
| Dizziness | 2 | 0 | 0 | 0 |
| Headache | 1 | 0 | 1 | 0 |
| Infusion site pain | 1 | 0 | 1 | 0 |
| Myalgia | 1 | 1 | 0 | 0 |
| Neutropenia | 0 | 0 | 1 | 1 |
| Pain | 1 | 1 | 0 | 0 |
| Vomiting | 2 | 0 | 0 | 0 |
| Abdominal pain | 0 | 1 | 0 | 0 |
| Agitation | 1 | 0 | 0 | 0 |
| Alopecia | 0 | 0 | 1 | 0 |
| Anaemia | 0 | 0 | 1 | 0 |
| Asthenia | 0 | 0 | 1 | 0 |
| Blood bilirubin increased | 1 | 0 | 0 | 0 |
| Blood creatine phosphokinase increased | 1 | 0 | 0 | 0 |
| Dyspnoea | 0 | 1 | 0 | 0 |
| Fatigue | 1 | 0 | 0 | 0 |
| Hot flush | 1 | 0 | 0 | 0 |
| Hypersensitivity | 0 | 0 | 1 | 0 |
| Malaise | 0 | 1 | 0 | 0 |
| Muscle fatigue | 1 | 0 | 0 | 0 |
| Neck pain | 1 | 0 | 0 | 0 |
| Paraesthesia | 0 | 0 | 1 | 0 |
| Pruritus | 0 | 1 | 0 | 0 |
| Pyrexia | 0 | 1 | 0 | 0 |
| Sacral pain | 0 | 0 | 1 | 0 |
| Spinal pain | 0 | 0 | 1 | 0 |
| Vascular access complication | 0 | 1 | 0 | 0 |
Collected over 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.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Age 12 to < 18 Years, 5 mg/kg | 1/50 (2%) | 18/50 (36%) | 46/50 (92%) |
| Age 6 to < 12 Years, 5 mg/kg | 0/13 (0%) | 9/13 (69.2%) | 13/13 (100%) |
| Age 6 to < 12 Years, 8.5 mg/kg | 0/40 (0%) | 20/40 (50%) | 36/40 (90%) |
| Age 2 to < 6 Years, 8.5 mg/kg | 0/14 (0%) | 12/14 (85.7%) | 13/14 (92.9%) |
| All Participants | 1/117 (0.9%) | 59/117 (50.4%) | 108/117 (92.3%) |
| Event | 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 | All Participants |
|---|---|---|---|---|---|
| PyrexiaGeneral disorders | 2/50 | 2/13 | 1/40 | 4/14 | 9/117 |
| PainGeneral disorders | 1/50 | 0/13 | 2/40 | 3/14 | 6/117 |
| PneumoniaInfections and infestations | 1/50 | 1/13 | 4/40 | 3/14 | 9/117 |
| Back painMusculoskeletal and connective tissue disorders | 1/50 | 0/13 | 0/40 | 3/14 | 4/117 |
| CholecystitisHepatobiliary disorders | 0/50 | 2/13 | 0/40 | 0/14 | 2/117 |
| COVID-19Infections and infestations | 4/50 | 0/13 | 1/40 | 2/14 | 7/117 |
| AnaemiaBlood and lymphatic system disorders | 2/50 | 1/13 | 5/40 | 1/14 | 9/117 |
| Bone marrow failureBlood and lymphatic system disorders | 0/50 | 1/13 | 0/40 | 0/14 | 1/117 |
| ConstipationGastrointestinal disorders | 0/50 | 1/13 | 0/40 | 0/14 | 1/117 |
| VomitingGastrointestinal disorders | 0/50 | 1/13 | 0/40 | 0/14 | 1/117 |
| Event | 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 | All Participants |
|---|---|---|---|---|---|
| PyrexiaGeneral disorders | 12/50 | 5/13 | 16/40 | 5/14 | 38/117 |
| Abdominal painGastrointestinal disorders | 10/50 | 5/13 | 12/40 | 1/14 | 28/117 |
| HeadacheNervous system disorders | 19/50 | 4/13 | 10/40 | 3/14 | 36/117 |
| CoughRespiratory, thoracic and mediastinal disorders | 5/50 | 2/13 | 9/40 | 5/14 | 21/117 |
| Upper respiratory tract infectionInfections and infestations | 9/50 | 1/13 | 2/40 | 4/14 | 16/117 |
| Back painMusculoskeletal and connective tissue disorders | 11/50 | 2/13 | 9/40 | 4/14 | 26/117 |
| VomitingGastrointestinal disorders | 14/50 | 2/13 | 4/40 | 1/14 | 21/117 |
| Pain in extremityMusculoskeletal and connective tissue disorders | 11/50 | 3/13 | 10/40 | 3/14 | 27/117 |
| SARS-CoV-2 test negativeInvestigations | 12/50 | 3/13 | 0/40 | 0/14 | 15/117 |
| ConstipationGastrointestinal disorders | 9/50 | 3/13 | 6/40 | 2/14 | 20/117 |
| Age, Categorical(Participants) | 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 |
|---|---|---|---|---|---|
| <=18 years | 50 | 13 | 40 | 14 | 117 |
| Between 18 and 65 years | 0 | 0 | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 | 0 | 0 |
| Age, Continuous(Years) | 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 |
|---|---|---|---|---|---|
| Mean | 15.00 ± 1.921 | 8.87 ± 1.745 | 9.29 ± 1.614 | 4.81 ± 0.868 | 11.15 ± 3.983 |
| Age, Customized(Participants) | 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 |
|---|---|---|---|---|---|
| 0 - <28 d | 0 | 0 | 0 | 0 | 0 |
| 28 d - <2 y | 0 | 0 | 0 | 0 | 0 |
| 2 y - <12 y | 0 | 13 | 40 | 14 | 67 |
| 12 y - <18 y | 50 | 0 | 0 | 0 | 50 |
| Sex: Female, Male(Participants) | 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 |
|---|---|---|---|---|---|
| Female | 29 | 5 | 17 | 5 | 56 |
| Male | 21 | 8 | 23 | 9 | 61 |
| Race (NIH/OMB)(Participants) | 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 |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 3 | 4 | 7 |
| Asian | 7 | 0 | 3 | 0 | 10 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 32 | 7 | 19 | 8 | 66 |
| White | 11 | 4 | 13 | 2 | 30 |
| More than one race | 0 | 2 | 2 | 0 | 4 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Data sharing details ↗ · www.clinicalstudydatarequest.com
Ran from Oct 2018 to primary completion in Nov 2024, 73 months.
Results were first posted in Jul 2025, 8 months after primary completion.
Of 34 industry-sponsored phase 2 interventional studies under Anemia, Sickle Cell, half reached primary completion within 28 months of starting (the median), counting those still running; a quarter within 16 and three quarters within 41. This study's 73 months is above that.
Counting every sponsor, half of 93 studies reached it within 46 months; a quarter within 24 and three quarters within 73.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Oct 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Crizanlizumab