Nomacopan (rVA576) in Transplant Associated Thrombotic Microangiopathy

Phase 3

Terminated

Brief Summary: Multicentre Study of nomacopan in Paediatric Haematopoietic Stem-Cell Transplant Associated Thrombotic Microangiopathy

Detailed Description: This is an open-label, multi-centre study of two-parts, Part A and B, includes 24 weeks of treatment, safety follow up after 30 days.

Part A: dose algorithm, safety and efficacy

Part B: safety and efficacy

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Patients weighing less than 5 kg.
Patients with a positive direct Coombs' test.
Patients who do not receive nomacopan within 21 days of the initial diagnosis of TMA.
Patients having an active systemic or organ system bacterial or fungal infection or progressive severe infection at the time of diagnosis of TMA
Grade 4 Acute graft-versus-host disease (GVHD)
Received eculizumab or any other complement blocker therapy at any time.
Known hypersensitivity to the active ingredient or excipients

If an enrolled patient has a positive ADAMTS13 test (<10%) returned from their screening assessment, the patient should be withdrawn from the study

Arm && Interventions

Group	Intervention	Description
nomacopan (rVA576)	nomacopan (rVA576)	The study population will consist of paediatric patients who have undergone allogeneic or autologous haematopoietic stem cell transplantation (HSCT) and develop transplant-associated thrombotic microangiopathy (HSCT-TMA) within a year of HSCT

Primary Outcome Measures

Name	Time	Method
Number of Participants NOT Requiring a Red Blood Bell Transfusion (Transfusion Independence) for 28 Days or More OR Number of Participants With a Urine Protein Creatinine Ratio Value of ≤ 2 mg/mg Maintained for 28 Days or More.	24 weeks	Red blood cell transfusion independence for ≥28 days immediately prior to any scheduled clinical visit up to Week 24 or Urine protein creatinine ratio ≤ 2 mg/mg maintained over ≥ 28 days immediately prior to any scheduled clinical visit up to week 24 Transfusion independence is defined as no RBC transfusion attributable to, or required to manage, thrombotic microangiopathy (TMA). Transfusions required for causes other than TMA will not be considered within the evaluation of the efficacy endpoints.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With a Normalised sC5b-9 Value (Where sC5b-9 is the Same Value as the Upper Limit of Normal or Less)	24 weeks	Plasma sC5b-9 ≤ upper limit of normal (ULN)
Number of Participants With a Normalised Lactate Dehydrogenase (LDH) Value (Where LDH is the Same Value as the Upper Limit of Normal or Less)	24 weeks	Lactate dehydrogenase (LDH) ≤ULN
Normalisation of Lab Parameters	24 weeks	Number of participants with a normalised haptoglobin value (where haptoglobin is within the normal ranges)
Number of Participants Not Requiring a Platelet Transfusion (Transfusion Independence) for 28 Days or More.	24 weeks	Transfusion independence is defined as no platelet transfusion attributable to, or required to manage, thrombotic microangiopathy (TMA). Transfusions required for causes other than TMA will not be considered within the evaluation of the efficacy endpoints.

Locations (9): Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Stanford Children's Hospital
🇺🇸
Palo Alto, California, United States
Duke University Medical Center, Children's Health Center
🇺🇸
Durham, North Carolina, United States
Children's Hospitall of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
🇵🇱
Wrocław, Poland
The Royal Marsden NHS Foundation Trust
🇬🇧
London, United Kingdom
St. Georges University Hospital
🇬🇧
London, United Kingdom
Great Ormond Street Hospital (GOSH)
🇬🇧
London, United Kingdom
Royal Manchester Children's Hospital
🇬🇧
Manchester, United Kingdom
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States