Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ravulizumab in Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04543591
Recruitment Status : Active, not recruiting
First Posted : September 10, 2020
Last Update Posted : April 22, 2022
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE August 17, 2020
First Posted Date  ICMJE September 10, 2020
Last Update Posted Date April 22, 2022
Actual Study Start Date  ICMJE September 16, 2020
Estimated Primary Completion Date August 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 2, 2020)
TMA Response [ Time Frame: 26 weeks (treatment period) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2022)
  • Time To TMA Response [ Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) ]
  • Proportion of Participants with a Loss of TMA Response [ Time Frame: 26 weeks (treatment period) ]
  • Change from Baseline in eGFR [ Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) ]
  • TMA Relapse [ Time Frame: During the Follow-up Period (183-365 Days after start of study medication) ]
  • Overall Survival [ Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) ]
  • Non-relapse Mortality [ Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) ]
  • Platelet Response [ Time Frame: 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.
  • 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 ≤ 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
Original Secondary Outcome Measures  ICMJE
 (submitted: September 2, 2020)
  • Time To TMA Response [ Time Frame: 26 weeks (treatment period) ]
  • TMA Relapse [ Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) ]
  • Overall Survival [ Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) ]
  • Non-relapse Mortality [ Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) ]
  • Platelet Response [ Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ravulizumab in Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Thrombotic Microangiopathy
Intervention  ICMJE
  • Biological: Ravulizumab
    Weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 8 weeks.
    Other Name: Ultomiris, ALXN1210
  • 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).
Study Arms  ICMJE
  • 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).

    Interventions:
    • Biological: Ravulizumab
    • Other: Best supportive care
  • Placebo Comparator: Placebo
    In Stage 2, participants randomized to the placebo arm will receive matching placebo plus BSC.
    Interventions:
    • Other: Placebo
    • Other: Best supportive care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 2, 2020)
184
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 29, 2024
Estimated Primary Completion Date August 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Israel,   Italy,   Japan,   Korea, Republic of,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04543591
Other Study ID Numbers  ICMJE ALXN1210-TMA-313
2020-000144-61 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Alexion Pharmaceuticals
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Alexion Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Alexion Pharmaceuticals
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP