Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger
Primary Purpose
Thrombotic Microangiopathy
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ravulizumab
Placebo
Best Supportive Care
Sponsored by
About this trial
This is an interventional treatment trial for Thrombotic Microangiopathy focused on measuring Complement, Trigger, Secondary thrombotic microangiopathy, Acute kidney injury
Eligibility Criteria
Inclusion Criteria:
- 18 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.
Exclusion Criteria:
- 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
- Use of any complement inhibitors within the past 3 years
- Respiratory failure requiring mechanical ventilation
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Ravulizumab
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Complete TMA Response
Secondary Outcome Measures
Time to Complete TMA Response
Hematologic Response
Renal Response
On Dialysis
Change in Kidney Function as measured by estimated glomerular filtration rate (eGFR) in mL/min/1.73m^2
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04743804
Brief Title
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
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
Recruitment Challenges
Study Start Date
July 1, 2021 (Actual)
Primary Completion Date
November 21, 2022 (Actual)
Study Completion Date
December 22, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombotic Microangiopathy
Keywords
Complement, Trigger, Secondary thrombotic microangiopathy, Acute kidney injury
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ravulizumab
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Biological
Intervention Name(s)
Ravulizumab
Other Intervention Name(s)
Ultomiris, ALXN1210
Intervention Description
Body weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 8 weeks.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Matching placebo
Intervention Type
Other
Intervention Name(s)
Best Supportive Care
Intervention Description
Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).
Primary Outcome Measure Information:
Title
Complete TMA Response
Time Frame
26 weeks (treatment period)
Secondary Outcome Measure Information:
Title
Time to Complete TMA Response
Time Frame
26 weeks (treatment period)
Title
Hematologic Response
Time Frame
26 weeks (treatment period) and through study completion, an average of 1 year
Title
Renal Response
Time Frame
Through study completion, an average of 1 year
Title
On Dialysis
Time Frame
Proportion of participants on dialysis at Week 26
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 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.
Exclusion Criteria:
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
Use of any complement inhibitors within the past 3 years
Respiratory failure requiring mechanical ventilation
Facility Information:
Facility Name
Clinical Trial Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Clinical Trial Site
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Clinical Trial Site
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Clinical Trial Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Clinical Trial Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Clinical Trial Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Clinical Trial Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Clinical Trial Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Clinical Trial Site
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Clinical Trial Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Clinical Trial Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Clinical Trial Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Clinical Trial Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Clinical Trial Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
Clinical Trial Site
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
Clinical Trial Site
City
Bruxelles
Country
Belgium
Facility Name
Clinical Trial Site
City
Leuven
Country
Belgium
Facility Name
Clinical Trial Site
City
Liege
Country
Belgium
Facility Name
Clinical Trial Site
City
Montreal
Country
Canada
Facility Name
Clinical Trial Site
City
Toronto
Country
Canada
Facility Name
Clinical Trial Site
City
Bordeaux
Country
France
Facility Name
Clinical Trial Site
City
Chambery
Country
France
Facility Name
Clinical Trial Site
City
Lille
Country
France
Facility Name
Clinical Trial Site
City
Montpellier
Country
France
Facility Name
Clinical Trial Site
City
Paris
Country
France
Facility Name
Clinical Trial Site
City
Tours
Country
France
Facility Name
Clinical Trial Site
City
Bergamo
Country
Italy
Facility Name
Clinical Trial Site
City
Rome
Country
Italy
Facility Name
Clinical Trial Site
City
Iruma-gun
Country
Japan
Facility Name
Clinical Trial Site
City
Miyagi
Country
Japan
Facility Name
Clinical Trial Site
City
Miyazaki City
Country
Japan
Facility Name
Clinical Trial Site
City
Nagoya
Country
Japan
Facility Name
Clinical Trial Site
City
Osaka
Country
Japan
Facility Name
Clinical Trial Site
City
Sapporo
Country
Japan
Facility Name
Clinical Trial Site
City
Shinjuku-ku
Country
Japan
Facility Name
Clinical Trial Site
City
Tokyo
Country
Japan
Facility Name
Clinical Trial Site
City
Daegu
Country
Korea, Republic of
Facility Name
Clinical Trial Site
City
Gwangju
Country
Korea, Republic of
Facility Name
Clinical Trial Site
City
Seoul
Country
Korea, Republic of
Facility Name
Clinical Trial Site
City
Amsterdam
Country
Netherlands
Facility Name
Clinical Trial Site
City
Nijmegen
Country
Netherlands
Facility Name
Clinical Trial Site
City
Barcelona
Country
Spain
Facility Name
Clinical Trial Site
City
Granada
Country
Spain
Facility Name
Clinical Trial Site
City
Madrid
Country
Spain
Facility Name
Clinical Trial Site
City
Kaohsiung
Country
Taiwan
Facility Name
Clinical Trial Site
City
Taichung
Country
Taiwan
Facility Name
Clinical Trial Site
City
Taipei
Country
Taiwan
Facility Name
Clinical Trial Site
City
Liverpool
Country
United Kingdom
Facility Name
Clinical Trial Site
City
London
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Newcastle
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Nottingham
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Oxford
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Salford
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger
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