Back to resultsNomacopan (rVA576) in Transplant Associated Thrombotic Microangiopathy
Primary Purpose
Thrombotic Microangiopathies
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
nomacopan (rVA576)
Sponsored by
About this trial
This is an interventional treatment trial for Thrombotic Microangiopathies
Eligibility Criteria
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%),
Sites / Locations
- Children's Hospital Los AngelesRecruiting
- Stanford Children's HospitalRecruiting
- Duke University Medical Center, Children's Health CenterRecruiting
- Children's Hospitall of PhiladelphiaRecruiting
- Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we WroclawiuRecruiting
- Great Ormond Street Hospital (GOSH)Recruiting
- Royal Manchester Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
nomacopan (rVA576)
Arm Description
The study population will consist of paediatric patients who have undergone allogeneic or autologous HSCT and develop HSCT-TMA within 100 days of HSCT
Outcomes
Primary Outcome Measures
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.
Urine protein creatinine ratio ≤ 2 mg/mg
Urine protein creatinine ratio ≤ 2 mg/mg
Secondary Outcome Measures
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
Platelet transfusion independence
Platelet transfusion independence for ≥ 28 days within the 24 week timeframe
Normalisation of lab parameters
Serum sC5b-9 ≤ ULN
Normalisation of lab parameters
Lactate dehydrogenase (LDH) ≤ULN
Normalisation of lab parameters
Normalization of haptoglobin
Safety and tolerability of nomacopan
New or worsening AEs after dosing of investigational product will be recorded in the eCRF.
Safety and tolerability of nomacopan
Listings of subjects who have an SAE.
Safety and tolerability of nomacopan
Listings of subjects who discontinue from the study due to an AE.
Safety and tolerability of nomacopan
Occurrence of significant laboratory abnormalities will be summarized.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04784455
Brief Title
Nomacopan (rVA576) in Transplant Associated Thrombotic Microangiopathy
Official Title
Multicentre Study of Nomacopan (rVA576) in Paediatric Haematopoietic Stem-Cell Transplant Associated Thrombotic Microangiopathy
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2021 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AKARI Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombotic Microangiopathies
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
nomacopan (rVA576)
Arm Type
Experimental
Arm Description
The study population will consist of paediatric patients who have undergone allogeneic or autologous HSCT and develop HSCT-TMA within 100 days of HSCT
Intervention Type
Drug
Intervention Name(s)
nomacopan (rVA576)
Intervention Description
The study population will consist of paediatric patients who have undergone allogeneic or autologous HSCT and develop HSCT-TMA within 100 days of HSCT
Primary Outcome Measure Information:
Title
RBC transfusion independence for ≥ 28 days immediately prior to any scheduled clinical visit up to Week 24
Description
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.
Time Frame
24 weeks
Title
Urine protein creatinine ratio ≤ 2 mg/mg
Description
Urine protein creatinine ratio ≤ 2 mg/mg
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Renal Function Improvement
Description
Percentage of patients who achieve the primary endpoint of urine protein creatinine ratio ≤ 2 mg/mg (the nephrotic threshold) for ≥ 28 days
Time Frame
24 weeks
Title
Platelet transfusion independence
Description
Platelet transfusion independence for ≥ 28 days within the 24 week timeframe
Time Frame
24 weeks
Title
Normalisation of lab parameters
Description
Serum sC5b-9 ≤ ULN
Time Frame
24 weeks
Title
Normalisation of lab parameters
Description
Lactate dehydrogenase (LDH) ≤ULN
Time Frame
24 weeks
Title
Normalisation of lab parameters
Description
Normalization of haptoglobin
Time Frame
24 weeks
Title
Safety and tolerability of nomacopan
Description
New or worsening AEs after dosing of investigational product will be recorded in the eCRF.
Time Frame
28 weeks
Title
Safety and tolerability of nomacopan
Description
Listings of subjects who have an SAE.
Time Frame
28 weeks
Title
Safety and tolerability of nomacopan
Description
Listings of subjects who discontinue from the study due to an AE.
Time Frame
28 weeks
Title
Safety and tolerability of nomacopan
Description
Occurrence of significant laboratory abnormalities will be summarized.
Time Frame
28 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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%),
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wynne W Davies, MD
Phone
02080040268
Email
medical.monitors@akaritx.com
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Neena Kapoor
Email
medical.monitors@akaritx.com
First Name & Middle Initial & Last Name & Degree
Neena Kapoor
Facility Name
Stanford Children's Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Shyr
Email
medical.monitors@akaritx.com
First Name & Middle Initial & Last Name & Degree
David Shyr
Facility Name
Duke University Medical Center, Children's Health Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vinod Prasad
Email
medical.monitors@akaritx.com
First Name & Middle Initial & Last Name & Degree
Vinod Prasad
Facility Name
Children's Hospitall of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Timothy Olson
Email
medical.monitors@akaritx.com
First Name & Middle Initial & Last Name & Degree
Timothy Olson
Facility Name
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
City
Wrocław
ZIP/Postal Code
50556
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Krzysztof Kalwak
Email
medical.monitors@akaritx.com
First Name & Middle Initial & Last Name & Degree
Krzysztof Kalwak
Facility Name
Great Ormond Street Hospital (GOSH)
City
London
ZIP/Postal Code
WC1N3JH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Chiesa
Email
medical.monitors@akaritx.com
First Name & Middle Initial & Last Name & Degree
Robert Chiesa
Facility Name
Royal Manchester Children's Hospital
City
Manchester
ZIP/Postal Code
M139WL
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Wynn
Email
medical.monitors@akaritx.com
First Name & Middle Initial & Last Name & Degree
Robert Wynn
12. IPD Sharing Statement
Plan to Share IPD
No
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Nomacopan (rVA576) in Transplant Associated Thrombotic Microangiopathy
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