Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger

NCT04743804 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: ALXN1210-TMA-3152020-005328-13
• Study Type: interventional
• Target: 16
• Locations: 13 countries
• Sites: 97

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.

Conditions

Thrombotic Microangiopathy

Keywords

Complement; Trigger; Secondary thrombotic microangiopathy; Acute kidney injury

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26

  TMA response required the following: 1) Normalization of platelet count without transfusion support during the prior 7 days. 2) Normalization of LDH. 3) Improvement in glomerular filtration rate (eGFR) of \>= 30% compared to baseline. Participants must meet each TMA criterion at 2 separate assessments obtained at least 24 hours apart, and any measurement in between.

  Week 26

Secondary Outcomes (5)

• Time to Complete TMA Response

  Baseline through Week 26

• Number of Participants With Hematologic Response at Week 26

  Week 26

• Number of Participants With Renal Response at Week 26

  Week 26

• Number of Participants On Dialysis at Week 26

  Week 26

• Change From Baseline in eGFR at Week 26

  Baseline, Week 26

Study Arms (2)

Ravulizumab

EXPERIMENTAL

Biological: Ravulizumab; Other: Best Supportive Care

Placebo

PLACEBO COMPARATOR

Other: Placebo; Other: Best Supportive Care

Interventions

Ravulizumab BIOLOGICAL

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

Also known as: Ultomiris, ALXN1210

Ravulizumab

Placebo OTHER

Matching placebo

Placebo

Best Supportive Care OTHER

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

Placebo; Ravulizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older
• Body weight ≥ 30 kilograms
• 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
• TMA associated with a trigger (autoimmune disease, infection, solid organ transplant, drugs, and malignant hypertension)
• 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.

You may not qualify if:

• Any known gene mutation that causes atypical hemolytic uremic syndrome (aHUS)
• Postpartum aHUS
• Known chronic kidney disease
• TMA due to hematopoietic stem cell transplantation ≤ 12 months of Screening
• Primary and secondary glomerular diseases other than lupus
• Diagnosis of primary antiphospholipid antibody syndrome
• Shiga toxin-producing Escherichia coli infections including but not limited to Shiga toxin-related hemolytic uremic syndrome
• Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' (ADAMTS13) deficiency (activity \< 5%)
• Positive direct Coombs test which in the judgement of the Investigator is indicative of a clinically significant immune-mediated hemolysis not due to TMA
• Clinical diagnosis of disseminated intravascular coagulation (DIC) in the judgement of the Investigator
• Presence of sepsis requiring vasopressors within 7 days prior to or during Screening
• Presence of monoclonal gammopathy including but not limited to multiple myeloma
• Known bone marrow insufficiency or failure evidenced by cytopenias
• Unresolved N. meningitidis infection
• 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

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (97)

Research Site

Tucson, Arizona, 85724, United States

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Orange, California, 92868, United States

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Washington D.C., District of Columbia, 20007, United States

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Gainesville, Florida, 32610, United States

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Lexington, Kentucky, 40536, United States

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Louisville, Kentucky, 40202, United States

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Boston, Massachusetts, 02111, United States

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Boston, Massachusetts, 02115, United States

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Boston, Massachusetts, 02118, United States

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Rochester, Minnesota, 55905, United States

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New York, New York, 10032, United States

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Valhalla, New York, 10595, United States

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Winston-Salem, North Carolina, 27103, United States

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Cleveland, Ohio, 44106, United States

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Cleveland, Ohio, 44195, United States

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Columbus, Ohio, 43203, United States

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Philadelphia, Pennsylvania, 19107, United States

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Pittsburgh, Pennsylvania, 15212, United States

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Salt Lake City, Utah, 84115, United States

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Morgantown, West Virginia, 26505, United States

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Belgium, 1200, Belgium

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Brussels, 1070, Belgium

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Edegem, 2650, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Belo Horizonte, 30150-221, Brazil

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Botucatu, 18618-687, Brazil

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Campinas, 13083-894, Brazil

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Fortaleza, 60430-375, Brazil

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Porto Alegre, 90110-270, Brazil

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Ribeirão Preto, 14051-040, Brazil

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Salvador, 41253-190, Brazil

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São Paulo, 04036-002, Brazil

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São Paulo, 05403-000, Brazil

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Kingston, Ontario, K7L 3N6, Canada

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Toronto, Ontario, M5B 1W8, Canada

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Montreal, Quebec, H2X 3E4, Canada

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Québec, Quebec, G1R 3S1, Canada

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Bordeaux, 33076, France

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Chambéry, 73011, France

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Lille, 59037, France

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Montpellier, France

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Paris, 75020, France

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Paris, 75571, France

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Tours, 37044, France

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Essen, 45147, Germany

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Hanover, 30625, Germany

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Bergamo, 24127, Italy

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Roma, 00168, Italy

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Bunkyō City, 113-8431, Japan

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Iruma-Gun, 350-0495, Japan

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Mitaka-shi, 181-8611, Japan

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Miyazaki, 889-1692, Japan

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Nagoya, 466-8560, Japan

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Nagoya, 466-8650, Japan

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Osaka, 565-0871, Japan

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Sapporo, 060-8648, Japan

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Sendai, 980-8574, Japan

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Shinjuku-ku, 162-8666, Japan

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Amsterdam, 1100 DD, Netherlands

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Groningen, 9713 GZ, Netherlands

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Maastricht, 6229 HX, Netherlands

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Nijmegen, 6500 HB, Netherlands

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Daegu, 42415, South Korea

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Gwangju, 61469, South Korea

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Seoul, 02841, South Korea

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Seoul, 03080, South Korea

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Seoul, 04401, South Korea

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Seoul, 06973, South Korea

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Seoul, 134-727, South Korea

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Seoul, 6591, South Korea

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Barcelona, 08036, Spain

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Granada, 18014, Spain

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Las Palmas de Gran Canaria, 35016, Spain

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Madrid, 28040, Spain

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Kaohsiung City, 81362, Taiwan

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Kaohsiung City, 833401, Taiwan

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New Taipei City, 23561, Taiwan

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Taichung, 40447, Taiwan

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Taichung, 40705, Taiwan

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Taipei, 11217, Taiwan

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Bristol, BS10 5NB, United Kingdom

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Carshalton, SM5 1AA, United Kingdom

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Exeter, EX2 5DW, United Kingdom

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Leicester, LE3 9QP, United Kingdom

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Liverpool, L7 8XP, United Kingdom

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London, NW1 2BH, United Kingdom

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London, NW3 2QG, United Kingdom

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London, SE1 9RT, United Kingdom

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London, SE5 9RS, United Kingdom

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London, SW17 0QT, United Kingdom

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Manchester, M13 9WL, United Kingdom

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Newcastle upon Tyne, NE1 4LP, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Oxford, OX3 9DU, United Kingdom

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Salford, M6 8HD, United Kingdom

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Stevenage, SG1 4AB, United Kingdom

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Related Publications (1)

• 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.

  PMID: 37094330 DERIVED

MeSH Terms

Conditions

Thrombotic Microangiopathies; Acute Kidney Injury

Interventions

ravulizumab

Condition Hierarchy (Ancestors)

Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Limitations and Caveats

Due to continued enrollment challenges, Alexion decided to terminate this study prematurely. There were no safety or efficacy concerns throughout the course of study. The planned interim analysis for sample size re-estimation and the planned primary analysis as specified in Protocol Amendment 2 were not conducted due to early termination of the study. No hypothesis testing or inferential statistical analysis for the purpose of treatment comparisons was performed due to small sample size.

Results Point of Contact

• Title: Alexion Pharmaceuticals, Inc.
• Organization: Alexion Pharmaceuticals, Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: February 8, 2021
• Study Start: June 29, 2021
• Primary Completion: December 22, 2022
• Study Completion: December 22, 2022
• Last Updated: October 1, 2024
• Results First Posted: December 12, 2023

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (20); TW (6); IT (2); BR (9); CA (4); FR (7); DE (2); KR (8); ES (4); BE (5); JP (10); NL (4); GB (16)