Nomacopan (rVA576) in Transplant Associated Thrombotic Microangiopathy

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

Detailed Description
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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

Official Title
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Multicentre Study of Nomacopan (rVA576) in Paediatric Haematopoietic Stem-Cell Transplant Associated Thrombotic Microangiopathy

Conditions
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Thrombotic Microangiopathies

Intervention / Treatment
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* Drug: nomacopan (rVA576)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 0.5 and < 18 years at the time of diagnosis of TMA. Undergone allogeneic or autologous HSCT. TMA diagnosis within 100 days of their first allogeneic or autologous HSCT. Clinical or histological diagnosis of TMA Provision of written informed consent. Provision of informed assent Exclusion Criteria: Patients weighing less than 5 kg. Patients with a positive direct Coomb's test. Patients who do not receive nomacopan within 14 days of the initial diagnosis of TMA. Patients having an active systemic or organ system bacterial or fungal infection or progressive severe infection Grade 4 Acute GVHD Received eculizumab or any other complement blocker therapy at any time. Known hypersensitivity to the active ingredient or excipients A positive ADAMTS13 test (<10%),

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, uncontrolled, multi-centre two-part study. Part A: dose algorithm, safety and efficacy Part B: safety and efficacy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nomacopan (rVA576)<br>The study population will consist of paediatric patients who have undergone allogeneic or autologous HSCT and develop HSCT-TMA within 100 days of HSCT | Drug: nomacopan (rVA576)<br>* The study population will consist of paediatric patients who have undergone allogeneic or autologous HSCT and develop HSCT-TMA within 100 days of HSCT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RBC transfusion independence for ≥ 28 days immediately prior to any scheduled clinical visit up to Week 24 | Transfusion independence is defined as no RBC or 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 primary efficacy endpoints. | 24 weeks | 
| Urine protein creatinine ratio ≤ 2 mg/mg | Urine protein creatinine ratio ≤ 2 mg/mg | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Function Improvement | Percentage of patients who achieve the primary endpoint of urine protein creatinine ratio ≤ 2 mg/mg (the nephrotic threshold) for ≥ 28 days | 24 weeks | 
| Platelet transfusion independence | Platelet transfusion independence for ≥ 28 days within the 24 week timeframe | 24 weeks | 
| Normalisation of lab parameters | Serum sC5b-9 ≤ ULN | 24 weeks | 
| Normalisation of lab parameters | Lactate dehydrogenase (LDH) ≤ULN | 24 weeks | 
| Normalisation of lab parameters | Normalization of haptoglobin | 24 weeks | 
| Safety and tolerability of nomacopan | New or worsening AEs after dosing of investigational product will be recorded in the eCRF. | 28 weeks | 
| Safety and tolerability of nomacopan | Listings of subjects who have an SAE. | 28 weeks | 
| Safety and tolerability of nomacopan | Listings of subjects who discontinue from the study due to an AE. | 28 weeks | 
| Safety and tolerability of nomacopan | Occurrence of significant laboratory abnormalities will be summarized. | 28 weeks |