Nomacopan (rVA576) in Transplant Associated Thrombotic Microangiopathy

Phase 3

Terminated

• Conditions: Thrombotic Microangiopathies
• Interventions: Drug: nomacopan (rVA576)

• Registration Number: NCT04784455
• Lead Sponsor: AKARI Therapeutics

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

Study Timeline

• Study First Submitted: 2020-11-19
• Study Start: 2021-02-01
• Study First Submitted QC: 2021-03-04
• Study First Posted: 2021-03-05
• Primary Completion: 2024-05-15
• Study Completion: 2024-05-15
• Status Verified: 2024-06
• Last Update Submitted: 2024-07-15
• Last Update Posted: 2024-07-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Aged ≥ 0.5 and < 18 years at the time of diagnosis of TMA.
2. Undergone allogeneic or autologous HSCT.
3. TMA diagnosis within a year of their allogeneic or autologous HSCT.
4. Clinical or histological diagnosis of TMA
5. Provision of written informed consent.
6. Provision of informed assent

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Exclusion Criteria

1. Patients weighing less than 5 kg.
2. Patients with a positive direct Coombs' test.
3. Patients who do not receive nomacopan within 21 days of the initial diagnosis of TMA.
4. Patients having an active systemic or organ system bacterial or fungal infection or progressive severe infection at the time of diagnosis of TMA
5. Grade 4 Acute GVHD
6. Received eculizumab or any other complement blocker therapy at any time.
7. 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10%) returned from their screening assessment, the patient should be withdrawn from the study

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
nomacopan (rVA576)	nomacopan (rVA576)	The study population will consist of paediatric patients who have undergone allogeneic or autologous HSCT and develop HSCT-TMA within a year of HSCT

Primary Outcome Measures

Name	Time	Method
RBC 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	24 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Renal Function Improvement	24 weeks	Percentage of patients who achieve the primary endpoint of urine protein creatinine ratio ≤ 2 mg/mg (the nephrotic threshold) for ≥ 28 days
Platelet transfusion independence	24 weeks	Platelet transfusion independence for ≥ 28 days
Normalisation of lab parameters	24 weeks	Normalization of haptoglobin
Safety and tolerability of nomacopan	28 weeks	Occurrence of significant laboratory abnormalities will be summarized.

Trial Locations

Locations (9)

St. Georges University Hospital; 🇬🇧 London, United Kingdom

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Duke University Medical Center, Children's Health Center; 🇺🇸 Durham, North Carolina, United States

Stanford Children's Hospital; 🇺🇸 Palo Alto, California, 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

Great Ormond Street Hospital (GOSH); 🇬🇧 London, United Kingdom

Royal Manchester Children's Hospital; 🇬🇧 Manchester, United Kingdom