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Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger

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: NCT04743804
Recruitment Status : Recruiting
First Posted : February 8, 2021
Last Update Posted : August 2, 2022
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Brief Summary:
This study will investigate the efficacy and safety of ravulizumab compared to placebo in adult participants with thrombotic microangiopathy (TMA) associated with a trigger. Participants will be randomized to receive either ravulizumab plus best supportive care or placebo plus best supportive care. The treatment period is 26 weeks followed by a 26-week off-treatment 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 : 100 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 to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants Who Have Thrombotic Microangiopathy Associated With a Trigger
Actual Study Start Date : July 1, 2021
Estimated Primary Completion Date : January 31, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Ravulizumab

Arm Intervention/treatment
Experimental: Ravulizumab Biological: Ravulizumab
Body 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 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. Complete TMA Response [ Time Frame: 26 weeks (treatment period) ]

Secondary Outcome Measures :
  1. Time to Complete TMA Response [ Time Frame: 26 weeks (treatment period) ]
  2. Hematologic Response [ Time Frame: 26 weeks (treatment period) and through study completion, an average of 1 year ]
  3. Renal Response [ Time Frame: Through study completion, an average of 1 year ]
  4. On Dialysis [ Time Frame: Proportion of participants on dialysis at Week 26 ]
  5. Change in Kidney Function as measured by estimated glomerular filtration rate (eGFR) in mL/min/1.73m^2 [ Time Frame: 26 weeks (treatment period) and through study completion, an average of 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 18 years of age or older
  2. Body weight ≥ 30 kilograms
  3. 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
  4. TMA associated with a trigger (autoimmune disease, infection, solid organ transplant, drugs, and malignant hypertension)
  5. Vaccinated against meningococcal infection (Neisseria meningitidis), within 3 years prior to, or at the time of, randomization. Participants who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive appropriate prophylactic antibiotics for at least 2 weeks after the vaccination. If participant cannot receive the meningococcal vaccine, then participant must be willing to receive antibiotic prophylaxis coverage against N. meningitidis during the entire Treatment Period and for 8 months following the final dose of study drug. Additional vaccination (Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae) may be considered based on individual patient condition.

Exclusion Criteria:

  1. Any known gene mutation that causes atypical hemolytic uremic syndrome (aHUS)
  2. Postpartum aHUS
  3. Known chronic kidney disease
  4. TMA due to hematopoietic stem cell transplantation ≤ 12 months of Screening
  5. Primary and secondary glomerular diseases other than lupus
  6. Diagnosis of primary antiphospholipid antibody syndrome
  7. Shiga toxin-producing Escherichia coli infections including but not limited to Shiga toxin-related hemolytic uremic syndrome
  8. Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' (ADAMTS13) deficiency (activity < 5%)
  9. Positive direct Coombs test which in the judgement of the Investigator is indicative of a clinically significant immune-mediated hemolysis not due to TMA
  10. Clinical diagnosis of disseminated intravascular coagulation (DIC) in the judgement of the Investigator
  11. Presence of sepsis requiring vasopressors within 7 days prior to or during Screening
  12. Presence of monoclonal gammopathy including but not limited to multiple myeloma
  13. Known bone marrow insufficiency or failure evidenced by cytopenias
  14. Unresolved N. meningitidis infection
  15. History of malignancy within 5 years of Screening with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence
  16. Use of any complement inhibitors within the past 3 years
  17. Respiratory failure requiring mechanical ventilation

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): NCT04743804


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: NCT04743804    
Other Study ID Numbers: ALXN1210-TMA-315
First Posted: February 8, 2021    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:
Complement
Trigger
Secondary thrombotic microangiopathy
Acute kidney injury
Additional relevant MeSH terms:
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Ravulizumab
Vascular Diseases
Thrombotic Microangiopathies
Cardiovascular Diseases
Thrombocytopenia
Blood Platelet Disorders
Hematologic Diseases
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs