Nomacopan (rVA576) in Transplant Associated Thrombotic Microangiopathy

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

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

Study Overview

• Status: Terminated
• Conditions: Thrombotic Microangiopathies
• Intervention / Treatment: Drug: nomacopan (rVA576)

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 Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Wrocław, Poland, 50556
    • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
• United Kingdom
  • London, United Kingdom, SM25PT
    • The Royal Marsden NHS Foundation Trust
  • London, United Kingdom, SW170QT
    • St. Georges University Hospital
  • London, United Kingdom, WC1N3JH
    • Great Ormond Street Hospital (GOSH)
  • Manchester, United Kingdom, M139WL
    • Royal Manchester Children's Hospital
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Palo Alto, California, United States, 94304
      • Stanford Children's Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center, Children's Health Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospitall of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 14 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

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 graft-versus-host disease (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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Normalised sC5b-9 Value (Where sC5b-9 is the Same Value as the Upper Limit of Normal or Less)	Plasma sC5b-9 ≤ upper limit of normal (ULN)	24 weeks
Number of Participants With a Normalised Lactate Dehydrogenase (LDH) Value (Where LDH is the Same Value as the Upper Limit of Normal or Less)	Lactate dehydrogenase (LDH) ≤ULN	24 weeks
Normalisation of Lab Parameters	Number of participants with a normalised haptoglobin value (where haptoglobin is within the normal ranges)	24 weeks
Number of Participants Not Requiring a Platelet Transfusion (Transfusion Independence) for 28 Days or More.	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.	24 weeks

Collaborators and Investigators

• Sponsor: AKARI Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): May 15, 2024
• Study Completion (Actual): May 15, 2024

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: March 4, 2021
• First Posted (Actual): March 5, 2021

Study Record Updates

• Last Update Posted (Estimated): June 5, 2025
• Last Update Submitted That Met QC Criteria: May 16, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cytopenia; Cardiovascular Diseases; Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia; Vascular Diseases; Thrombotic Microangiopathies
• Other Study ID Numbers: AK901

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No