A Phase 3, Open-label, Single Arm, Multicenter Study of Ravulizumab in Addition to Best Supportive Care in Pediatric Participants (from 1 month to <18 years of age) with Thrombotic Microangiopathy (TMA) after Hematopoietic Stem Cell Transplantation (HSCT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alexion Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

5 Feb 2021 → 27 May 2025

Decision date (initial)

2023-11-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Alexion Pharmaceuticals, Inc.

External identifiers

EU CT number

2023-507850-33-00

EudraCT number

2020-000761-16

ClinicalTrials.gov

NCT04557735

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Pharmacodynamic, Others, Therapy

To assess the efficacy of ravulizumab plus BSC in the treatment of pediatric participants with HSCT-TMA

Secondary objectives 1

1. Safety and tolerability of ALXN1210 and additional efficacy measures

Conditions and MedDRA coding

Hematopoietic stem cell transplant-associated thrombotic microangiopathy(HSCT- TMA)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001943-PIP02-20

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. ≥ 28 days of age up to < 18 years of age at the time of signing the informed consent
2. Participants who received HSCT within the past 12 months at the time of Screening
3. A TMA diagnosis, based on meeting all of the following criteria during the Screening Period and/or ≤ 14 days prior to the Screening Period : • De novo thrombocytopenia or platelet transfusion refractoriness • Any one of the following markers of hemolysis: −Lactate dehydrogenase > ULN for age, − Presence of schistocytes ≥ 2 high power field (HPF) or ≥ 1% in peripheral blood smear • Proteinuria on spot urinalysis • De novo anemia OR Presence of hypertension
4. Participants must have HSCT-TMA that persists for at least 72 hours after initial management of any triggering agent/condition
5. Body weight ≥ 5 kg at Screening or ≤7 days prior to the start of the Screening Period (date of consent)
6. Male or female contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
7. Vaccinated against meningococcal infections if clinically feasible, according to national guidelines and recommendationsfor immune reconstitution after HSCT. Participants must be re-vaccinated against Haemophilus influenzae type b (Hib) 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 posttransplant infection prophylaxis guidances including coverage against N. meningitidis for at least 2 weeks after meningococcal vaccination. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis guidance including coverage against N. meningitidis the entire Treatment Period and for 8 months following the final dose of ravulizumab.
8. Participants or their legally authorized representative must be capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent or assent form and in this protocol

Exclusion criteria 12

1. Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' (ADAMTS13) deficiency (activity < 5%)
2. Known Shiga toxin-related hemolytic uremic syndrome (ST-HUS)
3. Positive direct Coombs test
4. Clinical diagnosis or suspicion of disseminated intravascular coagulation (DIC)
5. Known bone marrow/graft failure for the current HSCT
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 within 7 days prior to enrollment
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. TMA response

Secondary endpoints 7

1. Time to TMA response
2. Change from baseline in TMA-associated organ dysfunction in renal system, cardiovascular system, pulmonary system, CNS, and GI system at 6 months and 1 year
3. TMA relapse during the follow-up period
4. Overall survival
5. Non-relapse mortality
6. Platelet response
7. Hematologic response

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alexion Pharmaceuticals Inc.

Sponsor organisation

Alexion Pharmaceuticals Inc.

Address

121 Seaport Boulevard

City

Boston

Postcode

02210-2050

Country

United States

Scientific contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Public contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Third parties 3

Locations

4 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 86 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications