Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger

NCT ID: NCT04743804

Last Updated: 2024-10-01

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-29

Study Completion Date

2022-12-22

Brief Summary

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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.

Detailed Description

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Conditions

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Thrombotic Microangiopathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Ravulizumab

Group Type EXPERIMENTAL

Ravulizumab

Intervention Type BIOLOGICAL

Body weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 8 weeks.

Best Supportive Care

Intervention Type OTHER

Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Matching placebo

Best Supportive Care

Intervention Type OTHER

Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).

Interventions

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Ravulizumab

Body weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 8 weeks.

Intervention Type BIOLOGICAL

Placebo

Matching placebo

Intervention Type OTHER

Best Supportive Care

Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).

Intervention Type OTHER

Other Intervention Names

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Ultomiris ALXN1210

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Tucson, Arizona, United States

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Orange, California, United States

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Washington D.C., District of Columbia, United States

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Gainesville, Florida, United States

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Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Rochester, Minnesota, United States

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New York, New York, United States

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Valhalla, New York, United States

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Winston-Salem, North Carolina, United States

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Cleveland, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Salt Lake City, Utah, United States

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Morgantown, West Virginia, United States

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Belgium, , Belgium

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Brussels, , Belgium

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Edegem, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Belo Horizonte, , Brazil

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Botucatu, , Brazil

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Campinas, , Brazil

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Fortaleza, , Brazil

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Porto Alegre, , Brazil

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Ribeirão Preto, , Brazil

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Salvador, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Kingston, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Bordeaux, , France

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Chambéry, , France

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Lille, , France

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Montpellier, , France

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Paris, , France

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Paris, , France

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Tours, , France

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Essen, , Germany

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Hanover, , Germany

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Bergamo, , Italy

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Roma, , Italy

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Bunkyō City, , Japan

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Iruma-Gun, , Japan

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Mitaka-shi, , Japan

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Miyazaki, , Japan

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Nagoya, , Japan

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Nagoya, , Japan

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Osaka, , Japan

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Sapporo, , Japan

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Sendai, , Japan

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Shinjuku-ku, , Japan

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Amsterdam, , Netherlands

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Groningen, , Netherlands

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Maastricht, , Netherlands

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Nijmegen, , Netherlands

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Daegu, , South Korea

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Gwangju, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Barcelona, , Spain

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Granada, , Spain

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Las Palmas de Gran Canaria, , Spain

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Madrid, , Spain

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Kaohsiung City, , Taiwan

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Kaohsiung City, , Taiwan

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New Taipei City, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Bristol, , United Kingdom

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Carshalton, , United Kingdom

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Exeter, , United Kingdom

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Leicester, , United Kingdom

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Liverpool, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Newcastle upon Tyne, , United Kingdom

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Nottingham, , United Kingdom

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Oxford, , United Kingdom

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Salford, , United Kingdom

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Stevenage, , United Kingdom

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Countries

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United States Belgium Brazil Canada France Germany Italy Japan Netherlands South Korea Spain Taiwan United Kingdom

References

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Werion A, Storms P, Zizi Y, Beguin C, Bernards J, Cambier JF, Dahan K, Dierickx D, Godefroid N, Hilbert P, Lambert C, Levtchenko E, Meyskens T, Poire X, van den Heuvel L, Claes KJ, Morelle J; UCLouvain TMA/HUS Network and KU Leuven TMA/HUS Network. Epidemiology, Outcomes, and Complement Gene Variants in Secondary Thrombotic Microangiopathies. Clin J Am Soc Nephrol. 2023 Jul 1;18(7):881-891. doi: 10.2215/CJN.0000000000000182. Epub 2023 Apr 21.

Reference Type DERIVED
PMID: 37094330 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2020-005328-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALXN1210-TMA-315

Identifier Type: -

Identifier Source: org_study_id

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