Study of Ravulizumab in Pediatric Participants With HSCT-TMA

NCT04557735 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: ALXN1210-TMA-3142020-000761-16
• Study Type: interventional
• Target: 41
• Locations: 7 countries
• Sites: 26

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.

Conditions

Thrombotic Microangiopathy

Keywords

Thrombotic Microangiopathy (TMA); Ultomiris; Ravulizumab; Hematopoietic Stem Cell Transplant

Outcome Measures

Primary Outcomes (1)

• Participants With Thrombotic Microangiopathy (TMA) Response

  The criteria for TMA response were: 1. Normalization of platelet count (defined as platelet count ≥ 50000 mm\^3 or \>=50% increase in platelet count) without transfusion support during the prior 7 days. 2. Normalization of lactate dehydrogenase (LDH, defined as LDH ≤ upper limit of normal \[ULN\]) and absence of schistocytes. 3. At least 50% reduction in protein/creatinine ratio from baseline. Participants must meet each TMA criterion at 2 separate assessments obtained at least 24 hours apart, with no criteria failures or more than 1 missed scheduled visit in between. Additionally, all intervals in which the criteria were met must overlap for at least 1 day.

  Up to Week 26

Secondary Outcomes (11)

• Time to TMA Response During the 26-Week Treatment Period

  Day 1 through Week 26

• Participants With Hematologic Response

  Up to Week 26

• Time to Hematologic Response During the 26-Week Treatment Period

  Day 1 through Week 26

• Participants With Hemoglobin Response

  Up to Week 26

• Participants With Platelet Response

  Up to Week 26

Study Arms (1)

Ravulizumab plus Best Supportive Care

EXPERIMENTAL

Participants will receive ravulizumab plus Best Supportive Care as background therapy.

Drug: Ravulizumab; Other: Best Supportive Care

Interventions

Ravulizumab DRUG

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.

Also known as: Ultomiris

Ravulizumab plus Best Supportive Care

Best Supportive Care OTHER

Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).

Ravulizumab plus Best Supportive Care

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• ≥ 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 after initial management of any triggering agent/condition.
• A TMA diagnosis based on meeting the laboratory-based 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 \<18 years of age must be re-vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae if clinically feasible.
• Participants or their legally authorized representative must be capable of giving signed informed consent or assent.

You may not qualify if:

• Thrombotic thrombocytopenic purpura (TTP) evidenced by ADAMTS13 deficiency.
• Known Shiga toxin-related hemolytic uremic syndrome as demonstrated by positive test.
• Positive direct Coombs test indicative of a clinically significant immune-mediated hemolysis not due to TMA.
• Clinical diagnosis of disseminated intravascular coagulation (DIC).
• Known bone marrow/graft failure for the current HSCT.
• Diagnosis of veno-occlusive disease (VOD) which is unresolved at the time of Screening.
• Human immunodeficiency virus (HIV) infection.
• Unresolved meningococcal disease.
• Presence of sepsis requiring vasopressor support.
• Pregnancy or breastfeeding.
• Hypersensitivity to murine proteins or to 1 of the excipients of Ravulizumab.
• 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.
• Respiratory failure requiring mechanical ventilation.
• Previously or currently treated with a complement inhibitor.
• Participation in an interventional treatment study of any therapy for TMA.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (26)

Research Site

Tucson, Arizona, 85724, United States

Location

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Aurora, Colorado, 80045, United States

Location

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Atlanta, Georgia, 30322, United States

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Chicago, Illinois, 60611, United States

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Portland, Oregon, 97239, United States

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Dallas, Texas, 75235, United States

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Salt Lake City, Utah, 84108, United States

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Madison, Wisconsin, 53792, United States

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Haifa, 91096, Israel

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Jerusalem, 91120, Israel

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Petah Tikva, 4920235, Israel

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Ramat Gan, 5265601, Israel

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Roma, 00165, Italy

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Fukushima, 960-1295, Japan

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Kobe, 650-0047, Japan

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Nagoya, 466-8560, Japan

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Osaka, 534-0021, Japan

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Seoul, 03080, South Korea

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Seoul, 5505, South Korea

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Barcelona, 08041, Spain

Location

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Esplugues de Llobregat, 8950, Spain

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Madrid, 28046, Spain

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Salamanca, 37007, Spain

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Birmingham, B4 6NH, United Kingdom

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Bristol, BS2 8BJ, United Kingdom

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Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Thrombotic Microangiopathies

Interventions

ravulizumab

Condition Hierarchy (Ancestors)

Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Results Point of Contact

• Title: Alexion Pharmaceuticals, Inc.
• Organization: Alexion Pharmaceuticals, Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2020
• First Posted: September 22, 2020
• Study Start: December 7, 2020
• Primary Completion: November 26, 2024
• Study Completion: May 27, 2025
• Last Updated: January 12, 2026
• Results First Posted: January 12, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IL (4); JP (4); KR (2); ES (4); GB (3); US (8); IT (1)