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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04543591




Registration number
NCT04543591
Ethics application status
Date submitted
17/08/2020
Date registered
10/09/2020

Titles & IDs
Public title
Ravulizumab in Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant
Scientific title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Ravulizumab in Adult and Adolescent Participants Who Have Thrombotic Microangiopathy (TMA) After Hematopoietic Stem Cell Transplant (HSCT)
Secondary ID [1] 0 0
ALXN1210-TMA-313
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Thrombotic Microangiopathy 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Ravulizumab
Other interventions - Placebo
Other interventions - Best supportive care

Experimental: Ravulizumab - In Stage 1, all participants will receive open-label ravulizumab plus Best Supportive Care (BSC).

In Stage 2, participants will receive blinded ravulizumab plus Best Supportive Care (BSC).

Placebo comparator: Placebo - In Stage 2, participants randomized to the placebo arm will receive matching placebo plus BSC.


Treatment: Other: Ravulizumab
Weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 8 weeks.

Other interventions: Placebo
Matching placebo

Other interventions: Best supportive care
Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
TMA Response
Timepoint [1] 0 0
26 weeks (treatment period)
Secondary outcome [1] 0 0
Time To TMA Response
Timepoint [1] 0 0
26 weeks (treatment period)
Secondary outcome [2] 0 0
Change from Baseline in eGFR
Timepoint [2] 0 0
26 weeks (treatment period) and 52 weeks
Secondary outcome [3] 0 0
Overall Survival
Timepoint [3] 0 0
Day 100, 26 weeks (treatment period), and 52 weeks
Secondary outcome [4] 0 0
Non-relapse Mortality
Timepoint [4] 0 0
Day 100, 26 weeks (treatment period), and 52 weeks
Secondary outcome [5] 0 0
Hematologic Response
Timepoint [5] 0 0
26 weeks (treatment period)
Secondary outcome [6] 0 0
TMA response and time to response for each individual component of TMA
Timepoint [6] 0 0
26 weeks (treatment period)
Secondary outcome [7] 0 0
Time to Hematologic Response
Timepoint [7] 0 0
26 weeks (treatment period)
Secondary outcome [8] 0 0
Hemoglobin Response
Timepoint [8] 0 0
26 weeks (treatment period)
Secondary outcome [9] 0 0
Partial Response
Timepoint [9] 0 0
26 weeks (treatment period)
Secondary outcome [10] 0 0
Loss of TMA Response
Timepoint [10] 0 0
26 weeks (treatment period)
Secondary outcome [11] 0 0
Duration of TMA Response
Timepoint [11] 0 0
26 weeks (treatment period) and 52 weeks
Secondary outcome [12] 0 0
Changes from Baseline in Haptoglobin, Platelets, LDH, and Hemoglobin
Timepoint [12] 0 0
26 weeks (treatment period) and 52 weeks
Secondary outcome [13] 0 0
Modified TMA Response
Timepoint [13] 0 0
26 weeks (treatment period)
Secondary outcome [14] 0 0
Change from baseline in TMA-associated organ dysfunction in renal system, cardiovascular system, pulmonary system, CNS, and GI system
Timepoint [14] 0 0
26 weeks (treatment period) and 52 weeks
Secondary outcome [15] 0 0
TMA Relapse
Timepoint [15] 0 0
Follow-up Period
Secondary outcome [16] 0 0
Platelet Response
Timepoint [16] 0 0
26 weeks (treatment period)

Eligibility
Key inclusion criteria
1. 12 years of age or older at time of consent/assent.
2. Received HSCT within the past 12 months.
3. Diagnosis of TMA that persists for at least 72 hours after initial management of any triggering agent/condition.
4. A TMA diagnosis based on meeting the laboratory-based criteria during the Screening Period and/or =14 days prior to the Screening Period.
5. Body weight = 30 kilograms at Screening or =7 days prior to the start of the Screening Period (date of consent).
6. Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception.
7. Participants must be vaccinated against meningococcal infections if clinically feasible. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis. Participants <18 years of age must be re-vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae if clinically feasible.
8. Participants or their legally authorized representative must be capable of giving signed informed consent or assent.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Thrombotic thrombocytopenic purpura (TTP) evidenced by ADAMTS13 deficiency
2. Known Shiga toxin-related hemolytic uremic syndrome as demonstrated by positive test.
3. Positive direct Coombs test indicative of a clinically significant immune-mediated hemolysis not due to TMA.
4. Clinical diagnosis of disseminated intravascular coagulation (DIC).
5. Known bone marrow/graft failure for the current HSCT.
6. Diagnosis of veno-occlusive disease which is unresolved at the time of Screening.
7. Human immunodeficiency virus (HIV) infection.
8. Unresolved meningococcal disease.
9. Presence of sepsis requiring vasopressor support.
10. Pregnancy or breastfeeding.
11. Hypersensitivity to murine proteins or to one of the excipients of ravulizumab.
12. Any ongoing or history of medical or psychological conditions unrelated to HSCT-TMA that could increase the risk to the participant or confound the outcome of the study.
13. Respiratory failure requiring mechanical ventilation.
14. Acute and/or chronic heart failure with an ejection fraction = 40%.
15. Previously or currently treated with a complement inhibitor.
16. Participation in an interventional treatment study of any therapy for TMA.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
26/12/2025
Actual
Sample size
Target
130
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Adelaide
Recruitment hospital [2] 0 0
Research Site - Murdoch
Recruitment hospital [3] 0 0
Research Site - Parkville
Recruitment hospital [4] 0 0
Research Site - Westmead
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
6150 - Murdoch
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment outside Australia
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United States of America
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Alabama
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Madrid
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Malaga
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Sutton
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Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Alexion Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Alexion Pharmaceuticals, Inc. (Sponsor)
Address 0 0
Country 0 0
Phone 0 0
1-855-752-2356
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04543591