Study of Ravulizumab in Pediatric Participants With HSCT-TMA

Study Overview
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Brief Summary
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This study will evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab administered by intravenous infusion to pediatric participants, from 1 month to < 18 years of age, with HSCT-TMA. The treatment period is 26 weeks, followed by a 26-week off-treatment follow-up period.

Official Title
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A Phase 3, Open-label, Single Arm, Multicenter Study of Ravulizumab in Addition to Best Supportive Care in Pediatric Participants With Thrombotic Microangiopathy (TMA) After Hematopoietic Stem Cell Transplantation (HSCT)

Conditions
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Thrombotic Microangiopathy

Intervention / Treatment
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* Drug: Ravulizumab
* Other: Best Supportive Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 28 days of age up to < 18 years of age at the time of signing the informed consent. Received HSCT within the past 12 months. Diagnosis of TMA that persists for at least 72 hours despite initial management. A TMA diagnosis based on meeting the select criteria during the Screening Period and/or <=14 days prior to the Screening Period. Body weight ≥ 5 kilograms at Screening or ≤7 days prior to the start of the Screening Period (date of consent). Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception. Participants must be vaccinated against meningococcal infections if clinically feasible. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis. Participants or their legally authorized representative must be capable of giving signed informed consent or assent Exclusion Criteria: Thrombotic thrombocytopenic purpura (TTP) evidenced by ADAMTS13 deficiency. Shiga toxin producing Escherichia coli infection. Positive direct Coombs test Clinical diagnosis of disseminated intravascular coagulation (DIC) Known bone marrow/graft failure. Diagnosis of veno-occlusive disease (VOD), regardless of severity. Human immunodeficiency virus (HIV) infection Unresolved meningococcal disease. Presence or suspicion of sepsis (treated or untreated). Pregnancy or breastfeeding. Respiratory failure requiring mechanical ventilation Previously or currently treated with a complement inhibitor Participation in an interventional treatment study of any therapy for TMA

Ages Eligible for Study
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Minimum Age: 28 Days
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ravulizumab plus Best Supportive Care<br>Participants will receive ravulizumab plus Best Supportive Care as background therapy. | Drug: Ravulizumab<br>* Weight-based doses of ravulizumab will be administered intravenously as a loading dose regimen followed by maintenance dosing every 4 or 8 weeks, depending upon weight.<br>* Other names: Ultomiris;Other: Best Supportive Care<br>* Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TMA Response |  | 26 weeks (treatment period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time To TMA Response |  | 26 weeks (treatment period) and through 52 weeks (includes treatment period and off-treatment follow- up period) | 
| TMA Relapse |  | Follow Up period (183-365 Days after start of study medication) | 
| Overall Survival |  | 26 weeks and 52 weeks | 
| Hematologic Response | Hematologic Response as assessed by blood tests to measure lactate dehydrogenase (LDH) and platelet count. If baseline platelet count ≤ 50,000/mm3, all of the following criteria must be met: - Absolute platelet count > 50,000/mm3 without platelet transfusion support during the prior 7 days [or] If baseline platelet count > 50,000/mm3, all of the following criteria must be met: - ≥ 50% increase in platelet count compared to baseline value Normalization of LDH and absence of schistocytes | 26 weeks and 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombotic Microangiopathy (TMA), Ultomiris, Ravulizumab, Hematopoietic Stem Cell Transplant