Register a trial

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
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
31/03/2026
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
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
United States of America
State/province [18] 0 0
Wisconsin
Country [19] 0 0
Belgium
State/province [19] 0 0
Antwerpen
Country [20] 0 0
Belgium
State/province [20] 0 0
Brugge
Country [21] 0 0
Belgium
State/province [21] 0 0
Bruxelles
Country [22] 0 0
Belgium
State/province [22] 0 0
Chênée
Country [23] 0 0
Belgium
State/province [23] 0 0
Leuven
Country [24] 0 0
Belgium
State/province [24] 0 0
Yvoir
Country [25] 0 0
Brazil
State/province [25] 0 0
Barretos
Country [26] 0 0
Brazil
State/province [26] 0 0
Cerqueira César
Country [27] 0 0
Brazil
State/province [27] 0 0
Florianópolis
Country [28] 0 0
Brazil
State/province [28] 0 0
Jaú
Country [29] 0 0
Brazil
State/province [29] 0 0
Porto Alegre
Country [30] 0 0
Brazil
State/province [30] 0 0
Rio de Janeiro
Country [31] 0 0
Brazil
State/province [31] 0 0
Salvador
Country [32] 0 0
Brazil
State/province [32] 0 0
Sao Jose Do Rio Preto
Country [33] 0 0
Brazil
State/province [33] 0 0
Sao Paulo
Country [34] 0 0
Brazil
State/province [34] 0 0
São Paulo
Country [35] 0 0
Canada
State/province [35] 0 0
Alberta
Country [36] 0 0
Canada
State/province [36] 0 0
Ontario
Country [37] 0 0
Canada
State/province [37] 0 0
Quebec
Country [38] 0 0
China
State/province [38] 0 0
Beijing
Country [39] 0 0
China
State/province [39] 0 0
Chengdu
Country [40] 0 0
China
State/province [40] 0 0
Guangzhou
Country [41] 0 0
China
State/province [41] 0 0
Hangzhou
Country [42] 0 0
China
State/province [42] 0 0
Hefei
Country [43] 0 0
China
State/province [43] 0 0
Shanghai
Country [44] 0 0
China
State/province [44] 0 0
Suzhou
Country [45] 0 0
China
State/province [45] 0 0
Tianjin
Country [46] 0 0
China
State/province [46] 0 0
Wuhan
Country [47] 0 0
France
State/province [47] 0 0
Angers
Country [48] 0 0
France
State/province [48] 0 0
La Tronche
Country [49] 0 0
France
State/province [49] 0 0
Lille
Country [50] 0 0
France
State/province [50] 0 0
Nice
Country [51] 0 0
France
State/province [51] 0 0
Paris
Country [52] 0 0
France
State/province [52] 0 0
Pierre Benite
Country [53] 0 0
France
State/province [53] 0 0
Toulouse
Country [54] 0 0
Germany
State/province [54] 0 0
Berlin
Country [55] 0 0
Germany
State/province [55] 0 0
Chemnitz
Country [56] 0 0
Germany
State/province [56] 0 0
Duesseldorf
Country [57] 0 0
Germany
State/province [57] 0 0
Halle (Saale)
Country [58] 0 0
Germany
State/province [58] 0 0
Hamburg
Country [59] 0 0
Germany
State/province [59] 0 0
Köln
Country [60] 0 0
Germany
State/province [60] 0 0
Mainz A. Rhein
Country [61] 0 0
Germany
State/province [61] 0 0
Muenster
Country [62] 0 0
Germany
State/province [62] 0 0
Ulm
Country [63] 0 0
Greece
State/province [63] 0 0
Athens
Country [64] 0 0
Greece
State/province [64] 0 0
Patras
Country [65] 0 0
Greece
State/province [65] 0 0
Thessaloniki
Country [66] 0 0
Israel
State/province [66] 0 0
Halfa
Country [67] 0 0
Israel
State/province [67] 0 0
Jerusalem
Country [68] 0 0
Israel
State/province [68] 0 0
Petah Tikva
Country [69] 0 0
Israel
State/province [69] 0 0
Ramat Gan
Country [70] 0 0
Italy
State/province [70] 0 0
Avellino
Country [71] 0 0
Italy
State/province [71] 0 0
Bologna
Country [72] 0 0
Italy
State/province [72] 0 0
Brescia
Country [73] 0 0
Italy
State/province [73] 0 0
Cuneo
Country [74] 0 0
Italy
State/province [74] 0 0
Firenze
Country [75] 0 0
Italy
State/province [75] 0 0
Milano
Country [76] 0 0
Italy
State/province [76] 0 0
Monza
Country [77] 0 0
Italy
State/province [77] 0 0
Napoli
Country [78] 0 0
Italy
State/province [78] 0 0
Pavia
Country [79] 0 0
Italy
State/province [79] 0 0
Roma
Country [80] 0 0
Italy
State/province [80] 0 0
Salerno
Country [81] 0 0
Italy
State/province [81] 0 0
San Giovanni Rotondo
Country [82] 0 0
Italy
State/province [82] 0 0
Torino
Country [83] 0 0
Italy
State/province [83] 0 0
Torrette Di Ancona
Country [84] 0 0
Italy
State/province [84] 0 0
Udine
Country [85] 0 0
Japan
State/province [85] 0 0
Akita-shi
Country [86] 0 0
Japan
State/province [86] 0 0
Anjo
Country [87] 0 0
Japan
State/province [87] 0 0
Chiba-shi
Country [88] 0 0
Japan
State/province [88] 0 0
Fukushima-shi
Country [89] 0 0
Japan
State/province [89] 0 0
Isehara-shi
Country [90] 0 0
Japan
State/province [90] 0 0
Kanazawa-shi
Country [91] 0 0
Japan
State/province [91] 0 0
Kobe-shi
Country [92] 0 0
Japan
State/province [92] 0 0
Kumamoto-shi
Country [93] 0 0
Japan
State/province [93] 0 0
Kurashiki-shi
Country [94] 0 0
Japan
State/province [94] 0 0
Minato-ku
Country [95] 0 0
Japan
State/province [95] 0 0
Okayama-shi
Country [96] 0 0
Japan
State/province [96] 0 0
Osaka-shi
Country [97] 0 0
Japan
State/province [97] 0 0
Osakasayama-shi
Country [98] 0 0
Japan
State/province [98] 0 0
Sapporo-shi
Country [99] 0 0
Japan
State/province [99] 0 0
Suita-shi
Country [100] 0 0
Japan
State/province [100] 0 0
Sunto-gun
Country [101] 0 0
Japan
State/province [101] 0 0
Tsukuba-shi
Country [102] 0 0
Japan
State/province [102] 0 0
Wakayama-shi
Country [103] 0 0
Korea, Republic of
State/province [103] 0 0
Goyang-si
Country [104] 0 0
Korea, Republic of
State/province [104] 0 0
Seoul
Country [105] 0 0
Korea, Republic of
State/province [105] 0 0
Suwon
Country [106] 0 0
Netherlands
State/province [106] 0 0
Groningen
Country [107] 0 0
Netherlands
State/province [107] 0 0
Maastricht
Country [108] 0 0
Poland
State/province [108] 0 0
Gdansk
Country [109] 0 0
Poland
State/province [109] 0 0
Warszawa
Country [110] 0 0
Spain
State/province [110] 0 0
Barcelona
Country [111] 0 0
Spain
State/province [111] 0 0
Granada
Country [112] 0 0
Spain
State/province [112] 0 0
L'Hospitalet de Llobregat
Country [113] 0 0
Spain
State/province [113] 0 0
Madrid
Country [114] 0 0
Spain
State/province [114] 0 0
Majadahonda
Country [115] 0 0
Spain
State/province [115] 0 0
Malaga
Country [116] 0 0
Spain
State/province [116] 0 0
Oviedo
Country [117] 0 0
Spain
State/province [117] 0 0
Palma de Mallorca
Country [118] 0 0
Spain
State/province [118] 0 0
Pamplona
Country [119] 0 0
Spain
State/province [119] 0 0
Salamanca
Country [120] 0 0
Spain
State/province [120] 0 0
San Sebastian
Country [121] 0 0
Spain
State/province [121] 0 0
Sevilla
Country [122] 0 0
Spain
State/province [122] 0 0
Valencia
Country [123] 0 0
Sweden
State/province [123] 0 0
Huddinge
Country [124] 0 0
Sweden
State/province [124] 0 0
Lund
Country [125] 0 0
United Kingdom
State/province [125] 0 0
Bristol
Country [126] 0 0
United Kingdom
State/province [126] 0 0
Glasgow
Country [127] 0 0
United Kingdom
State/province [127] 0 0
London
Country [128] 0 0
United Kingdom
State/province [128] 0 0
Manchester
Country [129] 0 0
United Kingdom
State/province [129] 0 0
Nottingham
Country [130] 0 0
United Kingdom
State/province [130] 0 0
Sutton
Country [131] 0 0
United Kingdom
State/province [131] 0 0
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
clinicaltrials@alexion.com
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