Ravulizumab in Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant

Thrombotic Microangiopathy Clinical Trial

Official 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04543591
• Other study ID #: ALXN1210-TMA-313
• Status: Recruiting
• Phase: Phase 3
• Start date: December 10, 2020
• Est. completion date: July 1, 2025

Study information

• Verified date: May 2024
• Source: Alexion Pharmaceuticals, Inc.
• Contact: Alexion Pharmaceuticals, Inc. (Sponsor)
• Phone: 1-855-752-2356
• Email: clinicaltrials[@]alexion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 106
• Est. completion date: July 1, 2025
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

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.

Related Conditions & MeSH terms

• Thrombotic Microangiopathies
• Thrombotic Microangiopathy
• Vascular Diseases

Intervention

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

Other:
• Placebo
Matching placebo
• Best supportive care
Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).

Locations

Country	Name	City	State
Australia	Research Site	Adelaide
Australia	Research Site	Murdoch
Australia	Research Site	Parkville
Australia	Research Site	Westmead
Belgium	Research Site	Antwerpen
Belgium	Research Site	Brugge
Belgium	Research Site	Bruxelles
Belgium	Research Site	Chênée
Belgium	Research Site	Leuven
Belgium	Research Site	Yvoir
Brazil	Research Site	Barretos
Brazil	Research Site	Cerqueira César
Brazil	Research Site	Florianópolis
Brazil	Research Site	Jaú
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Salvador
Brazil	Research Site	Sao Jose Do Rio Preto
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
China	Research Site	Suzhou
France	Research Site	Angers
France	Research Site	La Tronche
France	Research Site	Lille Cedex
France	Research Site	Nice
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Pierre Benite
France	Research Site	Toulouse Cedex 09
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Chemnitz
Germany	Research Site	Duesseldorf
Germany	Research Site	Halle (Saale)
Germany	Research Site	Hamburg
Germany	Research Site	Köln
Germany	Research Site	Mainz A. Rhein
Germany	Research Site	Muenster
Germany	Research Site	Ulm
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Patras
Greece	Research Site	Thessaloniki
Israel	Research Site	Halfa
Israel	Research Site	Jerusalem
Israel	Research Site	Petah Tikva
Israel	Research Site	Ramat Gan
Israel	Research Site	Ramat Gan
Italy	Research Site	Avellino
Italy	Research Site	Bologna
Italy	Research Site	Brescia
Italy	Research Site	Cuneo
Italy	Research Site	Firenze
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Monza
Italy	Research Site	Napoli
Italy	Research Site	Pavia
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Salerno
Italy	Research Site	San Giovanni Rotondo
Italy	Research Site	Torino
Italy	Research Site	Torino
Italy	Research Site	Torrette Di Ancona
Italy	Research Site	Udine
Japan	Research Site	Akita-shi
Japan	Research Site	Anjo
Japan	Research Site	Chiba-Shi
Japan	Research Site	Fukushima-shi
Japan	Research Site	Isehara-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kurashiki-shi
Japan	Research Site	Minato-ku
Japan	Research Site	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Suita-shi
Japan	Research Site	Sunto-gun
Japan	Research Site	Tsukuba-shi
Japan	Research Site	Wakayama-shi
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Netherlands	Research Site	Groningen
Netherlands	Research Site	Maastricht
Poland	Research Site	Gdansk
Poland	Research Site	Warszawa
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Granada
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Malaga
Spain	Research Site	Oviedo
Spain	Research Site	Palma de Mallorca
Spain	Research Site	Pamplona
Spain	Research Site	Salamanca
Spain	Research Site	San Sebastian
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Sweden	Research Site	Huddinge
Sweden	Research Site	Lund
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Sutton
United Kingdom	Research Site	Wirral
United States	Research Site	Atlanta	Georgia
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boston	Massachusetts
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Chicago	Illinois
United States	Research Site	Dallas	Texas
United States	Research Site	Durham	North Carolina
United States	Research Site	Fort Worth	Texas
United States	Research Site	Grosse Pointe Farms	Michigan
United States	Research Site	Hershey	Pennsylvania
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Kansas City	Kansas
United States	Research Site	Louisville	Kentucky
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Seattle	Washington
United States	Research Site	Tampa	Florida
United States	Research Site	Tucson	Arizona
United States	Research Site	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  China,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TMA Response		26 weeks (treatment period)
Secondary	Time To TMA Response		26 weeks (treatment period)
Secondary	Change from Baseline in eGFR		26 weeks (treatment period)
Secondary	Overall Survival		26 weeks (treatment period)
Secondary	Non-relapse Mortality		26 weeks (treatment period)
Secondary	Hematologic Response	Hematologic Response as assessed by blood tests to measure lactate dehydrogenase (LDH) and platelet count.; (1) If baseline platelet count = 50000/mm3, the following criteria must be met: - Absolute platelet count > 50,000/mm3 without platelet transfusion support during the prior 7 days [or]; If baseline platelet count > 50,000/mm3, the following criteria must be met: - = 50% increase in platelet count compared to baseline value without platelet transfusion support during the prior 7 days; 2) Normalization of LDH and absence of schistocytes	26 weeks (treatment period)