Clinical trial NCT04557735: Study of Ravulizumab in Pediatric Participants With HSCT-TMA
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Thrombotic Microangiopathy
Keywords: Thrombotic Microangiopathy (TMA)
Ultomiris
Ravulizumab
Hematopoietic Stem Cell Transplant
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-22
Enrollment: 41
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

1. ≥ 28 days 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 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 ≥ 5 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.

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 (VOD) 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 1 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. Previously or currently treated with a complement inhibitor.
15. Participation in an interventional treatment study of any therapy for TMA.

Primary outcomes:
measure: TMA Response
timeFrame: 26 weeks (treatment period)
Secondary outcomes:
measure: Time To TMA Response
timeFrame: 26 weeks (treatment period)
measure: TMA Relapse
timeFrame: 52 weeks (follow-up period)
measure: Overall Survival
timeFrame: 26 weeks (treatment period) and 52 weeks
measure: Proportion of Participants with Hematologic Response
timeFrame: 26 weeks (treatment period)
measure: Proportion of Participants with Platelet Response
timeFrame: 26 weeks (treatment period)
measure: Proportion of Participants with Change from Baseline in TMA-associated Organ Dysfunction
timeFrame: 26 weeks (treatment period) and 52 weeks
measure: Non-relapse mortality
timeFrame: 26 weeks (treatment period) and 52 weeks
measure: Time to TMA Response for each individual component of TMA Response for Participants who Demonstrate TMA Response
timeFrame: 26 weeks (treatment period)
measure: Time to Hematologic Response
timeFrame: 26 weeks (treatment period)
measure: Proportion of Participants with Hemoglobin Response
timeFrame: 26 weeks (treatment period)
measure: Proportion of Participants with Partial Response
timeFrame: 26 weeks (treatment period)
measure: Proportion of Participants with Loss of TMA Response
timeFrame: 26 weeks (treatment period)
measure: Duration of TMA Response
timeFrame: 26 weeks (treatment period) and 52 weeks
measure: Proportion of Participants with Changes from Baseline in Selected Laboratory Tests
timeFrame: 26 weeks (treatment period) and 52 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Madison
country: United States
facility: Research Site
state: Wisconsin
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Petach-Tikva
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Fukushima-shi
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Esplugues de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Salamanca
country: Spain
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Research Site
Study officials:
References: