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Ravulizumab in Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant

Sponsor
Alexion Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04543591
Collaborator
(none)
184
Enrollment
71
Locations
2
Arms
41.4
Anticipated Duration (Months)
2.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: Ravulizumab
  • Other: Placebo
  • Other: Best supportive care
 Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
184 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date :
Sep 16, 2020
Anticipated Primary Completion Date :
Aug 31, 2023
Anticipated Study Completion Date :
Feb 29, 2024

Arms and Interventions

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).

    Outcome Measures

    Primary Outcome Measures

    1. TMA Response [26 weeks (treatment period)]

    Secondary Outcome Measures

    1. Time To TMA Response [26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)]

    2. Proportion of Participants with a Loss of TMA Response [26 weeks (treatment period)]

    3. Change from Baseline in eGFR [26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)]

    4. TMA Relapse [During the Follow-up Period (183-365 Days after start of study medication)]

    5. Overall Survival [26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)]

    6. Non-relapse Mortality [26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)]

    7. Platelet Response [26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)]

      Concentration (mm^3) of platelets compared to baseline without transfusion support prior to the 7 days.

    8. Hematologic Response [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 ≤ 50000/mm3, 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, the following criteria must be met: - ≥ 50% increase in platelet count compared to baseline value without platelet transfusion support during the prior 7 days 2) Normalization of LDH and absence of schistocytes

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 despite initial management

    4. A TMA diagnosis based on meeting the select criteria during the Screening Period and/or <=14 days prior to the Screening Period.

    5. Body weight ≥ 30 kilograms at Screening.

    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.

    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. Shiga toxin producing Escherichia coli infection

    3. Positive direct Coombs test.

    4. Clinical diagnosis of disseminated intravascular coagulation (DIC).

    5. Known bone marrow/graft failure.

    6. Diagnosis of veno-occlusive disease.

    7. Human immunodeficiency virus (HIV) infection.

    8. Unresolved meningococcal disease.

    9. Presence of sepsis requiring vasopressor support.

    10. Pregnancy or breastfeeding.

    11. Previously or currently treated with a complement inhibitor.

    12. Respiratory failure requiring mechanical ventilation.

    13. Acute and/or chronic heart failure.

    14. Participation in an interventional treatment study of any therapy for TMA.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clinical Trial Site Tampa Florida United States 33612
    2 Clinical Trial Site Atlanta Georgia United States 30322
    3 Clinical Trial Site Chicago Illinois United States 60611
    4 Clinical Trial Site Chicago Illinois United States 60611
    5 Clinical Trial Site Indianapolis Indiana United States 46237
    6 Clinical Trial Site Grosse Pointe Farms Michigan United States 48236
    7 Clinical Trial Site Valhalla New York United States 10595
    8 Clinical Trial Site Charlotte North Carolina United States 28203
    9 Clinical Trial Site Durham North Carolina United States 27705
    10 Clinical Trial Site Pittsburgh Pennsylvania United States 15232
    11 Clinical Trial Site Milwaukee Wisconsin United States 53226
    12 Clinical Trial Site Brugge Belgium
    13 Clinical Trial Site Bruxelles Belgium
    14 Clinical Trial Site Chênée Belgium
    15 Clinical Trial Site Leuven Belgium
    16 Clinical Trial Site Yvoir Belgium
    17 Clinical Trial Site Toronto Canada
    18 Clinical Trial Site Angers France
    19 Clinical Trial Site La Tronche France
    20 Clinical Trial Manager Lille France
    21 Clinical Trial Site Nice France
    22 Clinical Trial Site Paris France
    23 Clinical Trial Site Pierre-Bénite France
    24 Clinical Trial Site Toulouse France
    25 Clinical Trial Site Haifa Israel
    26 Clinical Trial Site Ramat Gan Israel
    27 Clinical Trial Site Avellino Italy
    28 Clinical Trial Site Cuneo Italy
    29 Clinical Trial Site Firenze Italy
    30 Clinical Study Site Milano Italy
    31 Clinical Trial Site Milano Italy
    32 Clinical Trial Site Roma Italy
    33 Clinical Trial Site Rome Italy
    34 Clinical Trial Site Salerno Italy
    35 Clinical Trial Site San Giovanni Rotondo Italy
    36 Clinical Trial Site Torino Italy
    37 Clinical Trial Site Udine Italy
    38 Clinical Trial Site Akita Japan
    39 Clinical Trial Site Anjo Japan
    40 Clinical Study Site Chiba Japan
    41 Clinical Study Site Fukushima Japan
    42 Clinical Trial Site Isehara Japan
    43 Clinical Study Site Kanazawa Japan
    44 Clinical Trial Site Kobe Japan
    45 Clinical Trial Site Kumamoto Japan
    46 Clinical Trial Site Kurashiki Japan
    47 Clinical Trial Site Nagaizumi-chō Japan
    48 Clinical Trial Site Okayama Japan
    49 Clinical Trial Site Osakasayama Japan
    50 Clinical Trial Site Osaka Japan
    51 Clinical Trial Site Sapporo Japan
    52 Clinical Trial Site Suita Japan
    53 Clinical Trial Site Tsukuba Japan
    54 Clinical Trial Site Wakayama Japan
    55 Clinical Trial Site Goyang Korea, Republic of
    56 Clinical Trial Site Seoul Korea, Republic of
    57 Clinical Trial Site Suwon Korea, Republic of
    58 Clinical Trial Site Gdansk Poland
    59 Clinical Trial Site Barcelona Spain
    60 Clinical Trial Site Granada Spain
    61 Clinical Trial Site Madrid Spain
    62 Clinical Trial Site Majadahonda Spain
    63 Clinical Trial Site Málaga Spain
    64 Clinical Trial Site Oviedo Spain
    65 Clinical Trial Site Palma De Mallorca Spain
    66 Clinical Trial Site Pamplona Spain
    67 Clinical Trial Site Salamanca Spain
    68 Clinical Trial Site San Sebastián Spain
    69 Clinical Trial Site Sevilla Spain
    70 Clinical Trial Site Valencia Spain
    71 Clinical Trial Site Nottingham United Kingdom

    Sponsors and Collaborators

    • Alexion Pharmaceuticals

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Alexion Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT04543591
    Other Study ID Numbers:
    • ALXN1210-TMA-313
    • 2020-000144-61
    First Posted:
    Sep 10, 2020
    Last Update Posted:
    Aug 2, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Alexion Pharmaceuticals
    Thrombotic Microangiopathy (TMA) Ultomiris
    Ravulizumab
    Hematopoietic Stem Cell Transplant (HSCT) Transplant-associated TMA
    HSCT-TMA
    Additional relevant MeSH terms:
    Vascular Diseases
    Thrombotic Microangiopathies
    Ravulizumab

    Study Results

    No Results Posted as of Aug 2, 2022