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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04543591




Registration number
NCT04543591
Ethics application status
Date submitted
17/08/2020
Date registered
10/09/2020
Date last updated
3/05/2024

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
Other interventions - 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.


Other interventions: 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
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)
Secondary outcome [3] 0 0
Overall Survival
Timepoint [3] 0 0
26 weeks (treatment period)
Secondary outcome [4] 0 0
Non-relapse Mortality
Timepoint [4] 0 0
26 weeks (treatment period)
Secondary outcome [5] 0 0
Hematologic Response
Timepoint [5] 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 despite initial management

4. A TMA diagnosis based on meeting the select 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.

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. Shiga toxin producing Escherichia coli infection

3. Positive direct Coombs test.

4. Clinical diagnosis of disseminated intravascular coagulation (DIC).

5. Known bone marrow/graft failure.

6. Diagnosis of veno-occlusive disease.

7. Human immunodeficiency virus (HIV) infection.

8. Unresolved meningococcal disease.

9. Presence of sepsis requiring vasopressor support.

10. Pregnancy or breastfeeding.

11. Previously or currently treated with a complement inhibitor.

12. Respiratory failure requiring mechanical ventilation.

13. Acute and/or chronic heart failure.

14. 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
1/07/2025
Actual
Sample size
Target
106
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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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alexion Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of
ravulizumab in adult and adolescent participants with hematopoietic stem cell
transplant-associated thrombotic microangiopathy (HSCT-TMA). In Stage 1, an open-label,
single-arm period, the dosing regimen will be confirmed. In Stage 2, participants will be
randomized to receive either blinded ravulizumab plus best supportive care or matching
placebo plus best supportive care. The treatment period is 26 weeks (open-label for Stage 1,
and randomized, double-blind, and placebo-controlled for Stage 2) followed by a 26-week
follow-up period.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04543591
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
clinicaltrials@alexion.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04543591