Study of Ravulizumab in Pediatric Participants With HSCT-TMA

February 16, 2024 updated by: Alexion Pharmaceuticals, Inc.

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

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Bron, France
        • Recruiting
        • Clinical Trial Site
      • Nantes, France
        • Recruiting
        • Clinical Trial Site
      • Paris, France
        • Recruiting
        • Clinical Trial Site
      • Strasbourg, France
        • Recruiting
        • Clinical Trial Site
      • Vandœuvre-lès-Nancy, France
        • Recruiting
        • Clinical Trial Site
  • Germany
      • Berlin, Germany
        • Recruiting
        • Clinical Trial Site
      • Freiburg, Germany
        • Recruiting
        • Clinical Trial Site
      • Halle, Germany
        • Recruiting
        • Clinical Trial Site
      • Tuebingen, Germany
        • Recruiting
        • Clinical Trial Site
  • Israel
      • Jerusalem, Israel
        • Recruiting
        • Clinical Trial Site
      • Petach-Tikva, Israel
        • Recruiting
        • Clinical Trial Site
      • Ramat Gan, Israel
        • Recruiting
        • Clinical Trial Site
  • Italy
      • Bologna, Italy
        • Recruiting
        • Clinical Trial Site
      • Brescia, Italy
        • Recruiting
        • Clinical Trial Site
      • Firenze, Italy
        • Recruiting
        • Clinical Trial Site
      • Genova, Italy
        • Recruiting
        • Clinical Trial Site
      • Monza, Italy
        • Recruiting
        • Clinical Trial Site
      • Pavia, Italy
        • Recruiting
        • Clinical Trial Site
      • Rome, Italy
        • Recruiting
        • Clinical Trial Site
      • Torino, Italy
        • Recruiting
        • Clinical Trial Site
      • Verona, Italy
        • Recruiting
        • Clinical Trial Site
  • Japan
      • Fukuoka, Japan
        • Recruiting
        • Clinical Trial Site
      • Fukushima, Japan
        • Recruiting
        • Clinical Study Site
      • Kobe, Japan
        • Recruiting
        • Clinical Trial Site
      • Nagoya, Japan
        • Recruiting
        • Clinical Trial Site
      • Osaka, Japan
        • Recruiting
        • Clinical Trial Site
      • Osakasayama, Japan
        • Recruiting
        • Clinical Trial Site
      • Saitama, Japan
        • Recruiting
        • Clinical Trial Site
      • Setagaya-Ku, Japan
        • Recruiting
        • Clinical Trial Site
  • Korea, Republic of
      • Goyang, Korea, Republic of
        • Recruiting
        • Clinical Trial Site
      • Seoul, Korea, Republic of
        • Recruiting
        • Clinical Trial Site
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Clinical Trial Site
      • Esplugues De Llobregat, Spain
        • Recruiting
        • Clinical Trial Site
      • Madrid, Spain
        • Recruiting
        • Clinical Trial Site
      • Salamanca, Spain
        • Recruiting
        • Clinical Trial Site
      • Valencia, Spain
        • Recruiting
        • Clinical Trial Site
  • United Kingdom
      • Birmingham, United Kingdom
        • Recruiting
        • Clinical Trial Site
      • Bristol, United Kingdom
        • Recruiting
        • Clinical Trial Site
      • Leeds, United Kingdom
        • Recruiting
        • Clinical Trial Site
      • London, United Kingdom
        • Recruiting
        • Clinical Trial Site
      • Newcastle, United Kingdom
        • Recruiting
        • Clinical Trial Site
      • Wuerzburg, United Kingdom
        • Recruiting
        • Clinical Trial Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • Clinical Trial Site
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Recruiting
        • Clinical Trial Site
      • Tucson, Arizona, United States, 85724
        • Recruiting
        • Clinical Trial Site
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • Clinical Trial Site
      • San Francisco, California, United States, 94158
        • Recruiting
        • Clinical Trial Site
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • Clinical Trial Site
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Clinical Trial Site
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Clinical Trial Site
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • Clinical Trial Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 55414
        • Recruiting
        • Clinical Trial Site
      • Minneapolis, Minnesota, United States, 55455
        • Active, not recruiting
        • Clinical Trial Site
    • New York
      • Valhalla, New York, United States, 10595
        • Recruiting
        • Clinical Trial Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Recruiting
        • Clinical Trial Site
    • Ohio
      • Akron, Ohio, United States, 44308
        • Recruiting
        • Clinical Trial Site
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Clinical Trial Site
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Clinical Trial Site
    • Texas
      • Dallas, Texas, United States, 75235
        • Recruiting
        • Clinical Trial Site
      • Fort Worth, Texas, United States, 76104
        • Recruiting
        • Clinical Trial Site
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Clinical Trial Site
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • Clinical Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 15 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 1 month of age up to < 18 years of age at the time of signing the informed consent.
  2. Received HSCT within the past 6 months.
  3. Diagnosis of TMA that persists despite initial management of any triggering condition.
  4. Body weight ≥ 5 kilograms.
  5. Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception starting at Screening and continuing until at least 8 months after the last dose of ravulizumab.
  6. Participants must be vaccinated against meningococcal infections if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. Participants must be re-vaccinated against Haemophilus influenzae type b and Streptococcus pneumoniae if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. All participants should be administered coverage with prophylactic antibiotics according to institutional post-transplant infection prophylaxis guidances, including coverage against Neisseria meningitidis for at least 2 weeks after meningococcal vaccination. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis coverage against Neisseria meningitidis the entire Treatment Period and for 8 months following the final dose of ravulizumab.

Exclusion Criteria:

  1. Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' deficiency (activity < 5%).
  2. Known Shiga toxin-related hemolytic uremic syndrome.
  3. Positive direct Coombs test.
  4. Diagnosis or suspicion of disseminated intravascular coagulation.
  5. Known bone marrow/graft failure.
  6. Diagnosis of veno-occlusive disease (VOD).
  7. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer).
  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. Previously or currently treated with a complement inhibitor.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

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
Time Frame
TMA Response
Time Frame: 26 weeks (treatment period)
26 weeks (treatment period)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)
26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)
TMA Relapse
Time Frame: Follow Up period (183-365 Days after start of study medication)
Follow Up period (183-365 Days after start of study medication)
Time To TMA Response
Time Frame: 26 weeks (treatment period)
26 weeks (treatment period)
Hematologic Response
Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)

Hematologic Response as assessed by blood tests to measure lactate dehydrogenase (LDH) and platelet count.

  1. 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

  2. Normalization of LDH and absence of schistocytes
26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)
Proportion of Participants with Platelet Response ≥ 100,000/mm^3 without transfusion support
Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)
26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)
Number of Participants with a Change from Baseline in TMA-associated Organ Dysfunction in Renal System, Cardiovascular System, Pulmonary System, CNS, and GI System.
Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)]
26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)]
Proportion of Participants who die due to any cause during the study, with the exception of death due to underlying disease progression or relapse
Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)
26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexion Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 6, 2020

Primary Completion (Estimated)

December 30, 2024

Study Completion (Estimated)

June 30, 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)

February 21, 2024

Last Update Submitted That Met QC Criteria

February 16, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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