CClinicalTrials.gg
TerminatedNCT04784455Updated Jun 5, 2025Results posted

Nomacopan (rVA576) in Transplant Associated Thrombotic Microangiopathy

A Phase 3 interventional study of nomacopan (rVA576) in Thrombotic Microangiopathies, sponsored by AKARI Therapeutics. Terminated at 9 sites in 3 countries. Open to participants aged 6 Months to 18 Years. Per ClinicalTrials.gov, last updated 2025-06-05.

Sponsored by AKARI Therapeutics · Phase 3, Interventional, and Treatment

Why this study was terminated
The early termination of this study is a business decision following a portfolio reprioritization plan. The decision is not related to any Efficacy, Safety or Clinical concerns regarding Nomacopan/rVA576
Phase
Phase 3
Study type
Interventional
Enrollment
10
Allocation
Not applicable
Ages
6 Months to 18 Years
Sex
All
01

Study summary

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

Read the 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

02

Conditions studied

  • Thrombotic Microangiopathies
03

Who can participate

Ages eligible
6 Months to 18 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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10%) returned from their screening assessment, the patient should be withdrawn from the study

04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
10 participants (actual)

Study arms

  • 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)

Interventions

  • Drugnomacopan (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

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 24 weeks

Secondary outcomes

  1. 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)

    Time frame: 24 weeks

  2. 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

    Time frame: 24 weeks

  3. Normalisation of Lab Parameters

    Number of participants with a normalised haptoglobin value (where haptoglobin is within the normal ranges)

    Time frame: 24 weeks

  4. 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.

    Time frame: 24 weeks

06

Results

Posted May 15, 2025

Participant flow

The study population consists of paediatric patients who have undergone allogeneic or autologous haematopoietic stem cell transplantation (HSCT) and developed haematopoietic stem cell transplant associated thrombotic microangiopathy (HSCT-TMA) within a year of HSCT

Participant flow — Overall Study
MilestoneNomacopan
Started10
Completed6
Not completed4
Withdrew: Death4

Outcome measures

PrimaryNumber 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.

Time frame:
24 weeks
Reported as:
Count of participants · Participants
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.
ParticipantsNomacopan
RBC transfusion independent for ≥ 28 days2
Urine protein creatinine ratio (UPCR) ≤ 2 mg/mg for ≥ 28 days4
SecondaryNumber 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)

Time frame:
24 weeks
Reported as:
Count of participants · Participants
Number of Participants With a Normalised sC5b-9 Value (Where sC5b-9 is the Same Value as the Upper Limit of Normal or Less)
ParticipantsNomacopan
Number of Participants With a Normalised sC5b-9 Value (Where sC5b-9 is the Same Value as the Upper Limit of Normal or Less)10
SecondaryNumber 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

Time frame:
24 weeks
Reported as:
Count of participants · Participants
Number of Participants With a Normalised Lactate Dehydrogenase (LDH) Value (Where LDH is the Same Value as the Upper Limit of Normal or Less)
ParticipantsNomacopan
Number of Participants With a Normalised Lactate Dehydrogenase (LDH) Value (Where LDH is the Same Value as the Upper Limit of Normal or Less)2
SecondaryNormalisation of Lab Parameters

Number of participants with a normalised haptoglobin value (where haptoglobin is within the normal ranges)

Time frame:
24 weeks
Reported as:
Count of participants · Participants
Normalisation of Lab Parameters
ParticipantsNomacopan
Normalisation of Lab Parameters4
SecondaryNumber 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.

Time frame:
24 weeks
Reported as:
Count of participants · Participants
Number of Participants Not Requiring a Platelet Transfusion (Transfusion Independence) for 28 Days or More.
ParticipantsNomacopan
Number of Participants Not Requiring a Platelet Transfusion (Transfusion Independence) for 28 Days or More.0

Adverse events

Collected over Duration of the study (Maximum of 2 year follow-up). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Nomacopan - 1.7 mg/kg0/1 (0%)0/1 (0%)0/1 (0%)
Nomacopan - 1.3 mg/kg0/3 (0%)0/3 (0%)1/3 (33.3%)
Nomacopan - 1.0 mg/kg0/6 (0%)0/6 (0%)1/6 (16.7%)
Nomacopan - 0.30 mg/kg4/10 (40%)6/10 (60%)7/10 (70%)
Nomacopan - 0.45 mg/kg0/3 (0%)2/3 (66.7%)2/3 (66.7%)
Nomacopan - 0.60 mg/kg———
Most frequent serious events
Showing 10 of 12
Most frequent serious events
EventNomacopan - 1.7 mg/kgNomacopan - 1.3 mg/kgNomacopan - 1.0 mg/kgNomacopan - 0.30 mg/kgNomacopan - 0.45 mg/kgNomacopan - 0.60 mg/kg
Device related infectionInfections and infestations0/10/30/60/101/3—
HypoglycaemiaMetabolism and nutrition disorders0/10/30/60/101/3—
Posterior reversible encephalopathy syndromeNervous system disorders0/10/30/60/101/3—
Respiratory failureRespiratory, thoracic and mediastinal disorders0/10/30/62/101/3—
Multiple organ dysfunction syndromeGeneral disorders0/10/30/62/100/3—
Cardiac arrestCardiac disorders0/10/30/61/100/3—
CytopeniaBlood and lymphatic system disorders0/10/30/61/100/3—
Generalised oedemaGeneral disorders0/10/30/61/100/3—
Generalised tonic-clonic seizureNervous system disorders0/10/30/61/100/3—
HypertensionVascular disorders0/10/30/61/100/3—
Most frequent other events
Showing 10 of 19
Most frequent other events
EventNomacopan - 1.7 mg/kgNomacopan - 1.3 mg/kgNomacopan - 1.0 mg/kgNomacopan - 0.30 mg/kgNomacopan - 0.45 mg/kgNomacopan - 0.60 mg/kg
HyperkalaemiaMetabolism and nutrition disorders0/10/30/65/101/3—
PyrexiaGeneral disorders0/10/30/65/101/3—
AnaemiaBlood and lymphatic system disorders0/10/30/64/101/3—
LeukopeniaBlood and lymphatic system disorders0/10/30/64/101/3—
HypermagnesaemiaMetabolism and nutrition disorders0/10/30/64/101/3—
HypokalaemiaMetabolism and nutrition disorders0/10/30/63/101/3—
HypocalcaemiaMetabolism and nutrition disorders0/10/30/62/101/3—
HyponatraemiaMetabolism and nutrition disorders0/11/30/62/101/3—
HypophosphataemiaMetabolism and nutrition disorders0/10/30/62/101/3—
Blood bicarbonate decreasedInvestigations0/10/30/62/101/3—

Baseline characteristics

Age, Customized
Age, Customized(Participants)Nomacopan
≥ 0.5 to < 2 years1
≥ 2 to < 9 years3
≥ 9 to < 18 years6
Sex: Female, Male
Sex: Female, Male(Participants)Nomacopan
Female6
Male4
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Nomacopan
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American1
White9
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Nomacopan
United States1
United Kingdom9
07

Study locations

9 sites
  • Children's Hospital Los Angeles
    Los Angeles, California 90027, United States
  • Stanford Children's Hospital
    Palo Alto, California 94304, United States
  • Duke University Medical Center, Children's Health Center
    Durham, North Carolina 27710, United States
  • Children's Hospitall of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
  • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
    Wrocław, 50556, Poland
  • The Royal Marsden NHS Foundation Trust
    London, SM25PT, United Kingdom
  • St. Georges University Hospital
    London, SW170QT, United Kingdom
  • Great Ormond Street Hospital (GOSH)
    London, WC1N3JH, United Kingdom
  • Royal Manchester Children's Hospital
    Manchester, M139WL, United Kingdom
08

References and documents

Study documents

  • Study protocol · Nov 10, 2021
  • Statistical analysis plan · Feb 18, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT04784455
Lead sponsor
AKARI Therapeutics
Responsible party
Sponsor
First posted
Mar 5, 2021
Start date
Feb 1, 2021
Primary completion
May 15, 2024
Completion
May 15, 2024
Results posted
May 15, 2025
Last update
Jun 5, 2025

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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