Crizanlizumab for Pediatric Sickle Cell Disease

No longer recruiting at 87 trial locations

Overseen By Novartis Pharmaceuticals

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must be taking: HU/HC, L-glutamine

Must not be taking: Monoclonal antibodies, Voxelotor

Disqualifiers: Stem cell transplant, Bleeding disorders, HIV, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 107

Duration: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of crizanlizumab, a treatment for sickle cell disease, to assist children with the condition, especially those who have experienced a Vaso-Occlusive Crisis (VOC)—painful blockages in blood vessels—at least once in the past year. The goal is to determine the right dose and ensure safety for children, as it has already proven successful in adults. Children aged 2 to under 18 with sickle cell disease and a history of VOC might be suitable candidates, particularly if they have been on consistent medication like Hydroxyurea. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

If you are taking Hydroxyurea/Hydroxycarbamide, L-glutamine, or erythropoietin stimulating agents, you must have been on them for at least 6 months before the trial and continue at the same dose during the trial. If you are not on these medications, you must have been off them for at least 6 months before the trial. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that crizanlizumab is likely to be safe for pediatric patients?

Research shows that crizanlizumab is generally safe for people with sickle cell disease. Studies involving patients aged 12 to under 18 years found that a 5 mg/kg dose of crizanlizumab was well tolerated. These patients experienced no unexpected side effects, supporting its safety. Crizanlizumab has already been used in adults with sickle cell disease, where it proved safe and effective. This information helps predict its potential effectiveness in younger patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

Crizanlizumab is unique because it targets P-selectin, a protein that plays a crucial role in causing the blockages in blood vessels associated with sickle cell disease. Unlike standard treatments such as hydroxyurea, which works by increasing fetal hemoglobin, crizanlizumab helps to prevent red blood cells from sticking to vessel walls, thereby reducing pain crises. Researchers are excited about crizanlizumab because it offers a novel approach and has the potential to significantly decrease the frequency of these painful episodes in children with sickle cell disease.

What evidence suggests that crizanlizumab might be an effective treatment for sickle cell disease in pediatric patients?

Research has shown that crizanlizumab, which participants in this trial may receive, can reduce the number of painful episodes, known as vaso-occlusive crises, in people with sickle cell disease. Studies have found that this treatment significantly lessens these painful events. Specifically, evidence from adults and older children indicates that crizanlizumab improves symptoms safely. It also has a good safety record, meaning most patients tolerate it well. Overall, past research results are promising for using crizanlizumab to manage sickle cell disease. ^{1 3 4 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for pediatric patients aged 6 months to <18 years with sickle cell disease who've had at least one pain crisis in the past year. They must have been stable on certain medications if used, and have proper organ function. Those with recent blood transfusions, bleeding disorders, or severe illnesses are excluded.

Inclusion Criteria

I have been on the same dose of my medication for at least 6 months and plan to keep it the same during the trial.

I have been diagnosed with Sickle Cell Disease through blood tests.

My kidney and liver functions are within the required range.

Exclusion Criteria

I have had a stem cell transplant.

I have not received any blood products in the last 30 days.

I have an active Hepatitis B infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive crizanlizumab with or without hydroxyurea/hydroxycarbamide for 2 years

2 years

Visits on Week 1 Day 1, Week 3 Day 1, and Day 1 of every 4-week cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Post-treatment follow-up (last infusion +105 days)

What Are the Treatments Tested in This Trial?

Interventions

• Crizanlizumab

Trial Overview The study tests Crizanlizumab's dosing and safety in children with sickle cell disease over two years. It builds on adult trials by adjusting doses based on kids' responses. This open-label Phase II trial does not use a placebo group.

How Is the Trial Designed?

Group I: Crizanlizumab Experimental Treatment 1 Intervention

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.

Crizanlizumab is already approved in United States for the following indications:

Approved in United States as Adakveo for:

• Prevention of recurrent vaso-occlusive crises in sickle cell disease patients aged 16 years and older

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8255978/

Crizanlizumab for the Prevention of Vaso-Occlusive Pain ... Conclusion: Crizanlizumab appears to be an efficacious therapy for patients with sickle cell disease to reduce the frequency of vaso-occlusive crises. Concerns ...

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/180/530345/Pharmacokinetics-Pharmacodynamics-Safety-and

Pharmacokinetics/Pharmacodynamics, Safety, and Efficacy of ... The initial data from the 2-year analysis of 50 patients with SCD aged 12 to <18 years showed that crizanlizumab 5.0 mg/kg was safe and well ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03474965

NCT03474965 | Study of Dose Confirmation and Safety ... 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 ...

4. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00384-3/abstract

Crizanlizumab with or without hydroxyurea in patients ... Crizanlizumab 5·0 mg/kg exhibits a favorable safety profile in patients with sickle cell disease: pooled data from two phase II studies

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/761128s006lbl.pdf

ADAKVEO® (crizanlizumab-tmca) injection, for intravenous use ADAKVEO® is indicated to reduce the frequency of vaso-occlusive crises (VOCs) in adults and pediatric patients aged. 16 years and older with sickle cell disease ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8812070/

S122: SAFETY AND EFFICACY OF CRIZANLIZUMAB IN ... In this initial analysis, crizanlizumab 5 mg/kg was safe and well tolerated in patients with SCD aged 12–<18 years, consistent with the established profile of ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0268960X25000438

Review Evidence and gaps in clinical outcomes of novel ... In the SUSTAIN study, a 5-mg/kg dose of crizanlizumab reduced the occurrence of vaso-occlusive crises (VOCs) and hospitalizations by 45 % and 41 %, respectively ...