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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04543591
Recruitment Status : Recruiting
First Posted : September 10, 2020
Last Update Posted : August 2, 2022
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

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
Thrombotic Microangiopathy Biological: Ravulizumab Other: Placebo Other: Best supportive care Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : September 16, 2020
Estimated Primary Completion Date : August 31, 2023
Estimated Study Completion Date : February 29, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Ravulizumab

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 Name: 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).




Primary Outcome Measures :
  1. TMA Response [ Time Frame: 26 weeks (treatment period) ]

Secondary Outcome Measures :
  1. Time To TMA Response [ Time Frame: 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 [ Time Frame: 26 weeks (treatment period) ]
  3. Change from Baseline in eGFR [ Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) ]
  4. TMA Relapse [ Time Frame: During the Follow-up Period (183-365 Days after start of study medication) ]
  5. Overall Survival [ Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) ]
  6. Non-relapse Mortality [ Time Frame: 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) ]
  7. 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.

  8. 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




Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04543591


Contacts
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Contact: Alexion Pharmaceuticals Inc. 855-752-2356 clinicaltrials@alexion.com

Locations
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Sponsors and Collaborators
Alexion Pharmaceuticals
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Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04543591    
Other Study ID Numbers: ALXN1210-TMA-313
2020-000144-61 ( EudraCT Number )
First Posted: September 10, 2020    Key Record Dates
Last Update Posted: August 2, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Vascular Diseases
Thrombotic Microangiopathies
Cardiovascular Diseases
Thrombocytopenia
Blood Platelet Disorders
Hematologic Diseases
Ravulizumab
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs