Nomacopan (rVA576) in Transplant Associated Thrombotic Microangiopathy

Thrombotic Microangiopathies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04784455
• Other study ID #: AK901
• Status: Recruiting
• Phase: Phase 3
• Start date: February 1, 2021
• Est. completion date: December 2025

Study information

• Verified date: February 2024
• Source: AKARI Therapeutics
• Contact: Wynne W Davies, MD
• Phone: 02080040268
• Email: medical.monitors[@]akaritx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 18 Years

Eligibility

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 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10%) returned from their screening assessment, the patient should be withdrawn from the study

Related Conditions & MeSH terms

• Thrombotic Microangiopathies
• Vascular Diseases

Intervention

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

Locations

Country	Name	City	State
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu	Wroclaw
United Kingdom	Great Ormond Street Hospital (GOSH)	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United States	Duke University Medical Center, Children's Health Center	Durham	North Carolina
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Stanford Children's Hospital	Palo Alto	California
United States	Children's Hospitall of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AKARI Therapeutics

Countries where clinical trial is conducted

United States,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Urine protein creatinine ratio = 2 mg/mg	Urine protein creatinine ratio = 2 mg/mg	24 weeks
Secondary	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
Secondary	Platelet transfusion independence	Platelet transfusion independence for = 28 days within the 24 week timeframe	24 weeks
Secondary	Normalisation of lab parameters	Plasma sC5b-9 = ULN	24 weeks
Secondary	Normalisation of lab parameters	Lactate dehydrogenase (LDH) =ULN	24 weeks
Secondary	Normalisation of lab parameters	Normalization of haptoglobin	24 weeks
Secondary	Safety and tolerability of nomacopan	New or worsening AEs after dosing of investigational product will be recorded in the eCRF.	28 weeks
Secondary	Safety and tolerability of nomacopan	Listings of subjects who have an SAE.	28 weeks
Secondary	Safety and tolerability of nomacopan	Listings of subjects who discontinue from the study due to an AE.	28 weeks
Secondary	Safety and tolerability of nomacopan	Occurrence of significant laboratory abnormalities will be summarized.	28 weeks