Clinical trial NCT04743804: Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Thrombotic Microangiopathy
Keywords: Complement
Trigger
Secondary thrombotic microangiopathy
Acute kidney injury
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-02-08
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Number of Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26
timeFrame: Week 26
Secondary outcomes:
measure: Time to Complete TMA Response
timeFrame: Baseline through Week 26
measure: Number of Participants With Hematologic Response at Week 26
timeFrame: Week 26
measure: Number of Participants With Renal Response at Week 26
timeFrame: Week 26
measure: Number of Participants On Dialysis at Week 26
timeFrame: Week 26
measure: Change From Baseline in eGFR at Week 26
timeFrame: Baseline, Week 26
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Orange
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: New York
country: United States
facility: Research Site
state: New York
city: Valhalla
country: United States
facility: Research Site
state: New York
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
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state: Ohio
city: Columbus
country: United States
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state: Ohio
city: Philadelphia
country: United States
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state: Pennsylvania
city: Pittsburgh
country: United States
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state: Pennsylvania
city: Salt Lake City
country: United States
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state: Utah
city: Morgantown
country: United States
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state: West Virginia
city: Belgium
country: Belgium
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Edegem
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Liege
country: Belgium
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Botucatu
country: Brazil
facility: Research Site
city: Campinas
country: Brazil
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city: Fortaleza
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
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city: Ribeirão Preto
country: Brazil
facility: Research Site
city: Salvador
country: Brazil
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city: Sao Paulo
country: Brazil
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city: São Paulo
country: Brazil
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city: Kingston
country: Canada
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state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Montreal
country: Canada
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state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Chambéry Cedex
country: France
facility: Research Site
city: Lille
country: France
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city: Montpellier
country: France
facility: Research Site
city: PARIS Cedex 12
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Tours Cedex 09
country: France
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Bergamo
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Iruma-Gun
country: Japan
facility: Research Site
city: Mitaka-shi
country: Japan
facility: Research Site
city: Miyazaki-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Nagoya
country: Japan
facility: Research Site
city: Osaka
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Maastricht
country: Netherlands
facility: Research Site
city: Nijmegen
country: Netherlands
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Granada
country: Spain
facility: Research Site
city: Las Palmas de Gran Canaria
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Kaohsiung City
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
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city: New Taipei
country: Taiwan
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city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
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city: Bristol
country: United Kingdom
facility: Research Site
city: Carshalton
country: United Kingdom
facility: Research Site
city: Exeter
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
city: Stevenage
country: United Kingdom
facility: Research Site
Study officials:
References: