Study of Ravulizumab in Pediatric Participants With HSCT-TMA

Thrombotic Microangiopathy Clinical Trial

Official title:

A Phase 3, Open-label, Single Arm, Multicenter Study of Ravulizumab in Addition to Best Supportive Care in Pediatric Participants With Thrombotic Microangiopathy (TMA) After Hematopoietic Stem Cell Transplantation (HSCT)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04557735
• Other study ID #: ALXN1210-TMA-314
• Status: Recruiting
• Phase: Phase 3
• Start date: December 7, 2020
• Est. completion date: May 30, 2025

Study information

• Verified date: June 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 safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab administered by intravenous infusion to pediatric participants, from 1 month to < 18 years of age, with HSCT-TMA. The treatment period is 26 weeks, followed by a 26-week off-treatment follow-up period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: May 30, 2025
• Est. primary completion date: November 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

Inclusion Criteria:

1. 1 month of age up to < 18 years of age at the time of signing the informed consent.

2. Received HSCT within the past 12 months.

3. Diagnosis of TMA that persists despite initial management of any triggering condition.

4. Body weight = 5 kilograms.

5. 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.

6. Participants must be vaccinated against meningococcal infections if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. Participants must be re-vaccinated against Haemophilus influenzae type b and Streptococcus pneumoniae if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. All participants should be administered coverage with prophylactic antibiotics according to institutional post-transplant infection prophylaxis guidances, including coverage against Neisseria meningitidis for at least 2 weeks after meningococcal vaccination. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis coverage against Neisseria meningitidis the entire Treatment Period and for 8 months following the final dose of ravulizumab.

Exclusion Criteria:

1. Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' deficiency (activity < 5%).

2. Known Shiga toxin-related hemolytic uremic syndrome.

3. Positive direct Coombs test.

4. Diagnosis or suspicion of disseminated intravascular coagulation.

5. Known bone marrow/graft failure.

6. Diagnosis of veno-occlusive disease (VOD).

7. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer).

8. Unresolved meningococcal disease.

9. Presence of sepsis requiring vasopressor support.

10. Pregnancy or breastfeeding.

11. Hypersensitivity to murine proteins or to 1 of the excipients of Ravulizumab.

12. Previously or currently treated with a complement inhibitor.

Related Conditions & MeSH terms

• Thrombotic Microangiopathies
• Thrombotic Microangiopathy
• Vascular Diseases

Intervention

Drug:
• Ravulizumab
Weight-based doses of ravulizumab will be administered intravenously as a loading dose regimen followed by maintenance dosing every 4 or 8 weeks, depending upon weight.

Other:
• 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
France	Research Site	BRON Cedex
France	Research Site	Nantes cedex 01
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Strasbourg Cedex 2
France	Research Site	Vandoeuvre-Les-Nancy
Germany	Research Site	Berlin
Germany	Research Site	Freiburg
Germany	Research Site	Halle (Saale)
Germany	Research Site	Tuebingen
Germany	Research Site	Wuerzburg
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Petach-Tikva
Israel	Research Site	Ramat Gan
Italy	Research Site	Bologna
Italy	Research Site	Brescia
Italy	Research Site	Firenze
Italy	Research Site	Genova
Italy	Research Site	Monza
Italy	Research Site	Pavia
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Torino
Italy	Research Site	Verona
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Fukushima-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama
Japan	Research Site	Saitama-Shi
Japan	Research Site	Setagaya-ku
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
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Esplugues de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Salamanca
Spain	Research Site	Valencia
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United Kingdom	Research Site	Newcastle Upon Tyne
United States	Research Site	Akron	Ohio
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Birmingham	Alabama
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Cleveland	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Duarte	California
United States	Research Site	Fort Worth	Texas
United States	Research Site	Louisville	Kentucky
United States	Research Site	Madison	Wisconsin
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Phoenix	Arizona
United States	Research Site	Portland	Oregon
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Francisco	California
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,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Spain,  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	TMA Relapse		Follow Up period (183-365 Days after start of study medication)
Secondary	Overall Survival		26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)
Secondary	Hematologic Response	Hematologic Response as assessed by blood tests to measure lactate dehydrogenase (LDH) and platelet count.; If baseline platelet count = 50,000/mm3, all of 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, all of the following criteria must be met: - = 50% increase in platelet count compared to baseline value; Normalization of LDH and absence of schistocytes	26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)
Secondary	Proportion of Participants with Platelet Response = 100,000/mm^3 without transfusion support		26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)
Secondary	Number of Participants with a Change from Baseline in TMA-associated Organ Dysfunction in Renal System, Cardiovascular System, Pulmonary System, CNS, and GI System.		26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)]
Secondary	Proportion of Participants who die due to any cause during the study, with the exception of death due to underlying disease progression or relapse		26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)