Ravulizumab in Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Ravulizumab in Adult and Adolescent Participants Who Have Thrombotic Microangiopathy (TMA) After Hematopoietic Stem Cell Transplant (HSCT)

This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ravulizumab in adult and adolescent participants with hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA). In Stage 1, an open-label, single-arm period, the dosing regimen will be confirmed. In Stage 2, participants will be randomized to receive either blinded ravulizumab plus best supportive care or matching placebo plus best supportive care. The treatment period is 26 weeks (open-label for Stage 1, and randomized, double-blind, and placebo-controlled for Stage 2) followed by a 26-week follow-up period.

Study Overview

• Status: Completed
• Conditions: Thrombotic Microangiopathy
• Intervention / Treatment: Other: Placebo; Biological: Ravulizumab; Other: Best supportive care

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Parkville, Australia, 3050
    • Research Site
• Belgium
  • Bruges, Belgium, 8000
    • Research Site
  • Brussels, Belgium, 1200
    • Research Site
  • Chênée, Belgium, 4032
    • Research Site
  • Yvoir, Belgium, 5530
    • Research Site
• Brazil
  • Cerqueira César, Brazil, 05403-000
    • Research Site
  • Florianópolis, Brazil, 88034-000
    • Research Site
  • Jaú, Brazil, 17210-080
    • Research Site
  • Porto Alegre, Brazil, 90110-270
    • Research Site
  • Porto Alegre, Brazil, 90035-903
    • Research Site
  • Rio de Janeiro, Brazil, 20230-130
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
  • São Paulo, Brazil, 05.403-010
    • Research Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • Research Site
• China
  • Suzhou, China, 215006
    • Research Site
  • Tianjin, China, 300020
    • Research Site
• France
  • Angers, France, 49033
    • Research Site
  • La Tronche, France, 38043
    • Research Site
  • Nice, France, 06200
    • Research Site
• Germany
  • Hamburg, Germany, 20246
    • Research Site
  • Ulm, Germany, 89081
    • Research Site
• Greece
  • Athens, Greece, 12462
    • Research Site
  • Pátrai, Greece, 26504
    • Research Site
  • Thessaloniki, Greece, 57010
    • Research Site
• Israel
  • Halfa, Israel, 31096
    • Research Site
  • Ramat Gan, Israel, 52621
    • Research Site
• Italy
  • Roma, Italy, 00168
    • Research Site
  • Udine, Italy, 33100
    • Research Site
• Japan
  • Akita, Japan, 010-8543
    • Research Site
  • Anjo, Japan, 446-8602
    • Research Site
  • Chiba, Japan, 260-8677
    • Research Site
  • Fukushima, Japan, 960-1295
    • Research Site
  • Isehara-shi, Japan, 259-1193
    • Research Site
  • Kurashiki-shi, Japan, 710-8602
    • Research Site
  • Minatoku, Japan, 105-8470
    • Research Site
  • Okayama, Japan, 700-8558
    • Research Site
  • Osaka, Japan, 545-8586
    • Research Site
  • Osakasayama-shi, Japan, 589-8511
    • Research Site
  • Sapporo, Japan, 060-8638
    • Research Site
  • Suita-shi, Japan, 565-0871
    • Research Site
  • Tsukuba, Japan, 305-8576
    • Research Site
  • Wakayama, Japan, 641-8510
    • Research Site
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Research Site
• South Korea
  • Goyang-si, South Korea, 10408
    • Research Site
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 06351
    • Research Site
• Spain
  • Barcelona, Spain, 08036
    • Research Site
  • Granada, Spain, 18014
    • Research Site
  • L'Hospitalet de Llobregat, Spain, 08908
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Pamplona, Spain, 31008
    • Research Site
  • Salamanca, Spain, 37007
    • Research Site
  • Seville, Spain, 41013
    • Research Site
• Sweden
  • Huddinge, Sweden, 141 57
    • Research Site
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Research Site
  • Nottingham, United Kingdom, NG5 1PB
    • Research Site
• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Research Site
  • Michigan
    • Grosse Pointe Farms, Michigan, United States, 48236
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98109
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 12 years of age or older at time of consent/assent.
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 ≥ 30 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 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 one 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. Acute and/or chronic heart failure with an ejection fraction ≤ 40%.
15. Previously or currently treated with a complement inhibitor.
16. Participation in an interventional treatment study of any therapy for TMA.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ravulizumab; In Stage 1, all participants will receive open-label ravulizumab plus Best Supportive Care (BSC). In Stage 2, participants will receive blinded ravulizumab plus Best Supportive Care (BSC).	Biological: Ravulizumab; Weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 8 weeks.; Other Names: Ultomiris, ALXN1210; Other: Best supportive care; Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).
Placebo Comparator: Placebo; In Stage 2, participants randomized to the placebo arm will receive matching placebo plus BSC.	Other: Placebo; Matching placebo; Other: Best supportive care; Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival	Event free survival during the 26 weeks treatment period defined as the time from randomization until the first of the two following events: death and clinical worsening.	26 weeks (treatment period)

Secondary Outcome Measures

Outcome Measure	Time Frame
Time To TMA Response	26 weeks (treatment period)
Change from Baseline in eGFR	26 weeks (treatment period) and 52 weeks
Overall Survival	Day 100, 26 weeks (treatment period), and 52 weeks
Non-relapse Mortality	Day 100, 26 weeks (treatment period), and 52 weeks
Hematologic Response	26 weeks (treatment period)
TMA response and time to response for each individual component of TMA	26 weeks (treatment period)
Time to Hematologic Response	26 weeks (treatment period)
Hemoglobin Response	26 weeks (treatment period)
Partial Response	26 weeks (treatment period)
Loss of TMA Response	26 weeks (treatment period)
Duration of TMA Response	26 weeks (treatment period) and 52 weeks
Changes from Baseline in Haptoglobin, Platelets, LDH, and Hemoglobin	26 weeks (treatment period) and 52 weeks
Modified TMA Response	26 weeks (treatment period)
Change from baseline in TMA-associated organ dysfunction in renal system, cardiovascular system, pulmonary system, CNS, and GI system	26 weeks (treatment period) and 52 weeks
TMA Relapse	Follow-up Period
Platelet Response	26 weeks (treatment period)

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2020
• Primary Completion (Actual): September 19, 2025
• Study Completion (Actual): March 20, 2026

Study Registration Dates

• First Submitted: August 17, 2020
• First Submitted That Met QC Criteria: September 2, 2020
• First Posted (Actual): September 10, 2020

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Thrombotic Microangiopathy (TMA) Ultomiris; Ravulizumab; Hematopoietic Stem Cell Transplant (HSCT) Transplant-associated TMA; HSCT-TMA
• Additional Relevant MeSH Terms: Cytopenia; Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Substandard Drugs; Pharmaceutical Preparations; ravulizumab
• Other Study ID Numbers: ALXN1210-TMA-313; 2020-000144-61 (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