Study of Ravulizumab in Pediatric Participants With HSCT-TMA

Phase 3

Active, not recruiting

• Conditions: Thrombotic Microangiopathy
• Interventions: Drug: Ravulizumab; Other: Best Supportive Care

• Registration Number: NCT04557735
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-02
• Study First Submitted QC: 2020-09-18
• Study First Posted: 2020-09-22
• Study Start: 2020-12-07
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-12
• Last Update Posted: 2024-08-15
• Primary Completion: 2024-11-29
• Study Completion: 2025-05-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

1. ≥ 28 days of age up to < 18 years of age at the time of signing the informed consent.
2. Received HSCT within the past 12 months.
3. Diagnosis of TMA that persists for at least 72 hours after initial management of any triggering agent/condition.
4. A TMA diagnosis based on meeting the laboratory-based criteria during the Screening Period and/or ≤14 days prior to the Screening Period.
5. Body weight ≥ 5 kilograms at Screening or ≤7 days prior to the start of the Screening Period (date of consent).
6. Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception.
7. Participants must be vaccinated against meningococcal infections if clinically feasible. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis. Participants <18 years of age must be re-vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae if clinically feasible.
8. Participants or their legally authorized representative must be capable of giving signed informed consent or assent.

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Exclusion Criteria

1. Thrombotic thrombocytopenic purpura (TTP) evidenced by ADAMTS13 deficiency.
2. Known Shiga toxin-related hemolytic uremic syndrome as demonstrated by positive test.
3. Positive direct Coombs test indicative of a clinically significant immune-mediated hemolysis not due to TMA.
4. Clinical diagnosis of disseminated intravascular coagulation (DIC).
5. Known bone marrow/graft failure for the current HSCT.
6. Diagnosis of veno-occlusive disease (VOD) which is unresolved at the time of Screening.
7. Human immunodeficiency virus (HIV) infection.
8. Unresolved meningococcal disease.
9. Presence of sepsis requiring vasopressor support.
10. Pregnancy or breastfeeding.
11. Hypersensitivity to murine proteins or to 1 of the excipients of Ravulizumab.
12. Any ongoing or history of medical or psychological conditions unrelated to HSCT-TMA that could increase the risk to the participant or confound the outcome of the study.
13. Respiratory failure requiring mechanical ventilation.
14. Previously or currently treated with a complement inhibitor.
15. Participation in an interventional treatment study of any therapy for TMA.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ravulizumab plus Best Supportive Care	Best Supportive Care	Participants will receive ravulizumab plus Best Supportive Care as background therapy.
Ravulizumab plus Best Supportive Care	Ravulizumab	Participants will receive ravulizumab plus Best Supportive Care as background therapy.

Primary Outcome Measures

Name	Time	Method
TMA Response	26 weeks (treatment period)

Secondary Outcome Measures

Name	Time	Method
Proportion of Participants with Hematologic Response	26 weeks (treatment period)	Hematologic Response is measured by improvement in TMA markers (LDH, platelets, and schistocytes).
Time to Hematologic Response	26 weeks (treatment period)
Proportion of Participants with Hemoglobin Response	26 weeks (treatment period)	Hemoglobin Response is measured by stability of hemoglobin confirmed by two laboratory assessments at least 24h apart, after the lack of need for RBC transfusion for at least 7 days.
Time To TMA Response	26 weeks (treatment period)
Duration of TMA Response	26 weeks (treatment period) and 52 weeks
TMA Relapse	52 weeks (follow-up period)
Non-relapse mortality	26 weeks (treatment period) and 52 weeks
Proportion of Participants with Loss of TMA Response	26 weeks (treatment period)	Loss of TMA Response is measured in participants who met TMA Response criteria but no longer meet these criteria.
Proportion of Participants with Changes from Baseline in Selected Laboratory Tests	26 weeks (treatment period) and 52 weeks	Changes from baseline in haptoglobin are measured by blood tests assessing haptoglobin levels.; Changes from baseline in platelets are measured by blood tests assessing platelet counts.; Changes from baseline in LDH are measured by blood tests assessing LDH levels. Changes from baseline in hemoglobin are measured by blood tests assessing hemoglobin levels.
Overall Survival	26 weeks (treatment period) and 52 weeks
Proportion of Participants with Platelet Response	26 weeks (treatment period)	Platelet Response is determined by improvement in platelet count without the need for platelet transfusion.
Proportion of Participants with Change from Baseline in TMA-associated Organ Dysfunction	26 weeks (treatment period) and 52 weeks	Changes from baseline in the renal system are measured by improvements in laboratory tests (eGFR, protein/creatinine ratio, and serum creatinine).; Changes from baseline in the cardiovascular and pulmonary systems are measured by vital signs, Chest X-ray and/or Chest-CT, ECG, echocardiography, and changes in requirement for ventilatory/respiratory support.; Changes from baseline in the CNS are measured by posterior reversible encephalopathy syndrome (PRES) status.; Changes from baseline in the GI system are measured by reported AEs with GI involvement.
Time to TMA Response for each individual component of TMA Response for Participants who Demonstrate TMA Response	26 weeks (treatment period)	Time to TMA Response is measured by monitoring the time it takes to meet the criteria for TMA Response, based on lab assessment for TMA markers.
Proportion of Participants with Partial Response	26 weeks (treatment period)	Partial response is when the participant meets at least one of the TMA Response criteria, but not all.

Trial Locations

Locations (1)

Research Site; 🇬🇧 Newcastle Upon Tyne, United Kingdom