Study of Ravulizumab in Pediatric Participants With HSCT-TMA

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)

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.

Study Overview

• Status: Completed
• Conditions: Thrombotic Microangiopathy
• Intervention / Treatment: Other: Best Supportive Care; Drug: Ravulizumab

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 91096
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
  • Petah Tikva, Israel, 4920235
    • Research Site
  • Ramat Gan, Israel, 5265601
    • Research Site
• Italy
  • Roma, Italy, 00165
    • Research Site
• Japan
  • Fukushima, Japan, 960-1295
    • Research Site
  • Kobe, Japan, 650-0047
    • Research Site
  • Nagoya, Japan, 466-8560
    • Research Site
  • Osaka, Japan, 534-0021
    • Research Site
• South Korea
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 5505
    • Research Site
• Spain
  • Barcelona, Spain, 08041
    • Research Site
  • Esplugues de Llobregat, Spain, 8950
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Salamanca, Spain, 37007
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Research Site
  • Bristol, United Kingdom, BS2 8BJ
    • Research Site
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Research Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75235
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 13 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ravulizumab plus Best Supportive Care; Participants will receive ravulizumab plus Best Supportive Care as background therapy.

Other: Best Supportive Care; Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).; Drug: Ravulizumab; 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.; Other Names: Ultomiris

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to TMA Response During the 26-Week Treatment Period	Time to TMA response was defined as the time from first infusion to the first time point at which all criteria for TMA response was met. Participants were assigned as responders at the time of their TMA response and were censored at the earlier of last assessment with all 3 TMA response components available (including measurements collected after treatment discontinuation), or death if they did not respond by then. TMA response required the following: 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 LDH (defined as LDH ≤ULN) and absence of schistocytes. 3. At least 50% reduction in protein/creatinine ratio from baseline.	Day 1 through Week 26
Participants With Hematologic Response	Hematologic response required the following: (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 and (2) Normalization of LDH (defined as LDH ≤ULN) and absence of schistocytes.	Up to Week 26
Time to Hematologic Response During the 26-Week Treatment Period	Time to Hematologic response was defined as the time from first infusion to the first time point at which all criteria for hematologic response was met. Participants were assigned as responders at the time of their response and were censored at their discontinuation time or at the end of available follow-up if they did not respond by then. Hematologic response required the following: (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 and (2) Normalization of LDH (defined as LDH ≤ULN) and absence of schistocytes.	Day 1 through Week 26
Participants With Hemoglobin Response	Hemoglobin response was defined as the ability to maintain hemoglobin ≥ 10 g/dL without RBC transfusion support. The criterion must have been met at 2 separate assessments obtained at least 24 hours apart, and any measurement in between, and without RBC transfusion support during the prior 7 days.	Up to Week 26
Participants With Platelet Response	Normalization of platelet count was defined as baseline platelet count ≤ 50000 mm^3 or > 50000 mm^3, absolute platelet count > 50000 mm^3 or >=50% increase in platelet count without transfusion support during the prior 7 days.	Up to Week 26
Participants With Partial TMA Response	Partial response was defined as a participant meeting at least 1, but not all, criteria for TMA response. TMA response required the following: 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 LDH, (defined as LDH ≤ULN) and absence of schistocytes. 3. At least 50% reduction in protein/creatinine ratio from baseline.	Up to Week 26
Participants With Loss of TMA Response	Loss of response occurred when a participant who had previously achieved a TMA response failed to meet criteria for one or more components of TMA response at a subsequent visit in treatment period. At least one parameter must fail to meet response criteria at 2 separate assessments obtained at least 24 hours apart, and any measurement in between. TMA response required the following: 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 LDH (defined as LDH ≤ULN) and absence of schistocytes. 3. At least 50% reduction in protein/creatinine ratio from baseline.	Up to Week 26
Duration of TMA Response Through Week 52	This analysis includes data for each participant after TMA response through final follow-up. Participants with TMA response who do not experience these events are censored at their end of study date. TMA response required following: 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 LDH (defined as LDH ≤ULN) and absence of schistocytes. 3. At least 50% reduction in protein/creatinine ratio from baseline. The estimate is calculated based on Kaplan-Meier method.	Day 1 through Week 52
Participants With TMA Relapse	For participants that meet criteria for TMA response during 26-week Treatment Period, TMA relapse is defined as evidence of worsening hematologic and renal dysfunction due to TMA during post-treatment Follow-up Period that requires treatment intervention, as determined by Investigator. TMA response required the following: 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 LDH (defined as LDH ≤ULN) and absence of schistocytes. 3. At least 50% reduction in protein/creatinine ratio from baseline.	Up to Week 52
Overall Survival	The Kaplan-Meier method was used to measure overall survival estimate. Overall survival was calculated from date of treatment start to date of a documented death event (death due to any cause) or date of censoring. Participants who survived were censored at the earliest of an additional hematopoietic stem cell transplant (HSCT), Week 52, or their last known date alive.	Day 1 through Week 52
Non-relapse Mortality During the 52-Week Treatment Period	Cumulative incidence was estimated using a competing risk model. Non-relapse mortality was defined as a participant's death due to any cause during the study, with the exception of death due to underlying disease progression or relapse.	Day 1 through Week 52

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2020
• Primary Completion (Actual): November 26, 2024
• Study Completion (Actual): May 27, 2025

Study Registration Dates

• First Submitted: September 2, 2020
• First Submitted That Met QC Criteria: September 18, 2020
• First Posted (Actual): September 22, 2020

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Hematopoietic Stem Cell Transplant; Ravulizumab; Thrombotic Microangiopathy (TMA); Ultomiris
• Additional Relevant MeSH Terms: Cytopenia; Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Complement Inactivating Agents; ravulizumab
• Other Study ID Numbers: ALXN1210-TMA-314; 2020-000761-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No