Not provided
Not provided
Not provided
Not provided
Not provided
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
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Multicentre Study of nomacopan in Paediatric Haematopoietic Stem-Cell Transplant Associated Thrombotic Microangiopathy
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
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| nomacopan (rVA576) | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| nomacopan (rVA576) | Drug | The study population will consist of paediatric patients who have undergone allogeneic or autologous HSCT and develop HSCT-TMA within a year of HSCT |
|
| 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 |
| 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) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
If an enrolled patient has a positive ADAMTS13 test (<10%) returned from their screening assessment, the patient should be withdrawn from the study
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States | ||
| Stanford Children's Hospital |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Nomacopan | The trial was a 24-week open-label, non-comparative study in paediatric patients with HSCT-TMA. Patients will be given an ablating dose on Day 1, 12 hours apart which was determined by the child's weight on Day 1: Ablating Dose:
For children in the youngest two cohorts (≥ 0.5 to < 2 years, and ≥ 2 to < 9 years), the dose was re-calculated at the week 8 and week 16 visits using the child's new weight measured at that visit. The starting maintenance dose, administered 12 hours apart, from Day 2 until the end of treatment was 0.30 mg/kg for all 3 age groups. If required, from pre-dose Day 7 onwards, a dose escalation was permitted if the CH50 results were > 10 U Eq/mL and/or the unbound nomacopan in serum was < 55 ng/mL. Two dose escalations were permitted - an increase from the maintenance dose of 0.30 mg/kg to 0.45 mg/kg with a further increase to 0.60 mg/kg if required. Dose increases were preceded by an ablating dose as determined by age as per Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Nomacopan | The trial was a 24-week open-label, non-comparative study in paediatric patients with HSCT-TMA. Patients will be given an ablating dose on Day 1, 12 hours apart which was determined by the child's weight on Day 1: Ablating Dose:
For children in the youngest two cohorts (≥ 0.5 to < 2 years, and ≥ 2 to < 9 years), the dose was re-calculated at the week 8 and week 16 visits using the child's new weight measured at that visit. The starting maintenance dose, administered 12 hours apart, from Day 2 until the end of treatment was 0.30 mg/kg for all 3 age groups. If required, from pre-dose Day 7 onwards, a dose escalation was permitted if the CH50 results were > 10 U Eq/mL and/or the unbound nomacopan in serum was < 55 ng/mL. Two dose escalations were permitted - an increase from the maintenance dose of 0.30 mg/kg to 0.45 mg/kg with a further increase to 0.60 mg/kg if required. Dose increases were preceded by an ablating dose as determined by age as per Day 1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 24 weeks |
|
Duration of the study (Maximum of 2 year follow-up)
An ablating dose was given on Day 1, 12 hours apart which was determined by the child's age and weight on Day 1.
One patient was administered the 1.7 mg/kg ablation dose, 3 patients received the 1.3 mg/kg ablation dose and 6 patients received the 1.0 mg/kg ablation dose.
There were three maintenance dose levels - 0.3 mg/kg, 0.45 mg/kg and 0.60 mg/kg.
All ten patients started on 0.3 mg/kg. Three patients had a dose escalation to 0.45mg/kg. No patient were dose escalated to 0.60 mg/kg.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nomacopan - 1.7 mg/kg | The trial was a 24-week open-label, non-comparative study in paediatric patients with HSCT-TMA. Patients will be given an ablating dose on Day 1, 12 hours apart which was determined by the child's age and weight on Day 1: Ablating Dose:
One patient received the ablating dose of 1.7mg/kg. For children in the youngest two cohorts (≥ 0.5 to < 2 years, and ≥ 2 to < 9 years), the dose was re-calculated at the week 8 and week 16 visits using the child's new weight measured at that visit. The starting maintenance dose, administered 12 hours apart, from Day 2 until the end of treatment was 0.30 mg/kg for all 3 age groups. If required, from pre-dose Day 7 onwards, a dose escalation was permitted if the CH50 results were > 10 U Eq/mL and/or the unbound nomacopan in serum was < 55 ng/mL. Two dose escalations were permitted - an increase from the maintenance dose of 0.30 mg/kg to 0.45 mg/kg with a further increase to 0.60 mg/kg if required. Dose increases were preceded by an ablating dose as determined by age as per Day 1. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac arrest | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Scientific Officer | Akari Therapeutics | +44 208 004 0261 | miles.nunn@akaritx.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 10, 2021 | Mar 24, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 18, 2021 | Mar 24, 2025 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D057049 | Thrombotic Microangiopathies |
| ID | Term |
|---|---|
| D013921 | Thrombocytopenia |
| D001791 | Blood Platelet Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
Open-label, uncontrolled, multi-centre two-part study. Part A: dose algorithm, safety and efficacy Part B: safety and efficacy
Not provided
Not provided
Not provided
Not provided
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 |
| 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 | Wroclaw | 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 |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | 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) | Posted | Count of Participants | Participants | 24 weeks |
|
|
|
| Secondary | 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 | Posted | Count of Participants | Participants | 24 weeks |
|
|
|
| Secondary | Normalisation of Lab Parameters | Number of participants with a normalised haptoglobin value (where haptoglobin is within the normal ranges) | Posted | Count of Participants | Participants | 24 weeks |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 24 weeks |
|
|
|
| 0 |
| 1 |
| 0 |
| 1 |
| 0 |
| 1 |
| EG001 | Nomacopan - 1.3 mg/kg | The trial was a 24-week open-label, non-comparative study in paediatric patients with HSCT-TMA. Patients will be given an ablating dose on Day 1, 12 hours apart which was determined by the child's age and weight on Day 1: Ablating Dose:
Three patients received the ablating dose of 1.7mg/kg. For children in the youngest two cohorts (≥ 0.5 to < 2 years, and ≥ 2 to < 9 years), the dose was re-calculated at the week 8 and week 16 visits using the child's new weight measured at that visit. The starting maintenance dose, administered 12 hours apart, from Day 2 until the end of treatment was 0.30 mg/kg for all 3 age groups. If required, from pre-dose Day 7 onwards, a dose escalation was permitted if the CH50 results were > 10 U Eq/mL and/or the unbound nomacopan in serum was < 55 ng/mL. Two dose escalations were permitted - an increase from the maintenance dose of 0.30 mg/kg to 0.45 mg/kg with a further increase to 0.60 mg/kg if required. Dose increases were preceded by an ablating dose as determined by age as per Day 1. | 0 | 3 | 0 | 3 | 1 | 3 |
| EG002 | Nomacopan - 1.0 mg/kg | The trial was a 24-week open-label, non-comparative study in paediatric patients with HSCT-TMA. Patients will be given an ablating dose on Day 1, 12 hours apart which was determined by the child's age and weight on Day 1: Ablating Dose:
Six patients received the ablating dose of 1.7mg/kg. For children in the youngest two cohorts (≥ 0.5 to < 2 years, and ≥ 2 to < 9 years), the dose was re-calculated at the week 8 and week 16 visits using the child's new weight measured at that visit. The starting maintenance dose, administered 12 hours apart, from Day 2 until the end of treatment was 0.30 mg/kg for all 3 age groups. If required, from pre-dose Day 7 onwards, a dose escalation was permitted if the CH50 results were > 10 U Eq/mL and/or the unbound nomacopan in serum was < 55 ng/mL. Two dose escalations were permitted - an increase from the maintenance dose of 0.30 mg/kg to 0.45 mg/kg with a further increase to 0.60 mg/kg if required. Dose increases were preceded by an ablating dose as determined by age as per Day 1. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG003 | Nomacopan - 0.30 mg/kg | The trial was a 24-week open-label, non-comparative study in paediatric patients with HSCT-TMA. Patients will be given an ablating dose on Day 1, 12 hours apart which was determined by the child's age and weight on Day 1: Ablating Dose:
For children in the youngest two cohorts (≥ 0.5 to < 2 years, and ≥ 2 to < 9 years), the dose was re-calculated at the week 8 and week 16 visits using the child's new weight measured at that visit. The starting maintenance dose, administered 12 hours apart, from Day 2 until the end of treatment was 0.30 mg/kg for all 3 age groups. If required, from pre-dose Day 7 onwards, a dose escalation was permitted if the CH50 results were > 10 U Eq/mL and/or the unbound nomacopan in serum was < 55 ng/mL. Two dose escalations were permitted - an increase from the maintenance dose of 0.30 mg/kg to 0.45 mg/kg with a further increase to 0.60 mg/kg if required. Dose increases were preceded by an ablating dose as determined by age as per Day 1. 10 patient received the starting dose of 0.30 mg/kg | 4 | 10 | 6 | 10 | 7 | 10 |
| EG004 | Nomacopan - 0.45 mg/kg | The trial was a 24-week open-label, non-comparative study in paediatric patients with HSCT-TMA. Patients will be given an ablating dose on Day 1, 12 hours apart which was determined by the child's age and weight on Day 1: Ablating Dose:
For children in the youngest two cohorts (≥ 0.5 to < 2 years, and ≥ 2 to < 9 years), the dose was re-calculated at the week 8 and week 16 visits using the child's new weight measured at that visit. The starting maintenance dose, administered 12 hours apart, from Day 2 until the end of treatment was 0.30 mg/kg for all 3 age groups. If required, from pre-dose Day 7 onwards, a dose escalation was permitted if the CH50 results were > 10 U Eq/mL and/or the unbound nomacopan in serum was < 55 ng/mL. Two dose escalations were permitted - an increase from the maintenance dose of 0.30 mg/kg to 0.45 mg/kg with a further increase to 0.60 mg/kg if required. Dose increases were preceded by an ablating dose as determined by age as per Day 1. Of the 10 enrolled patients, 3 patients had a dose increase to 0.45 mg/kg | 0 | 3 | 2 | 3 | 2 | 3 |
| EG005 | Nomacopan - 0.60 mg/kg | The trial was a 24-week open-label, non-comparative study in paediatric patients with HSCT-TMA. Patients will be given an ablating dose on Day 1, 12 hours apart which was determined by the child's age and weight on Day 1: Ablating Dose:
For children in the youngest two cohorts (≥ 0.5 to < 2 years, and ≥ 2 to < 9 years), the dose was re-calculated at the week 8 and week 16 visits using the child's new weight measured at that visit. The starting maintenance dose, administered 12 hours apart, from Day 2 until the end of treatment was 0.30 mg/kg for all 3 age groups. If required, from pre-dose Day 7 onwards, a dose escalation was permitted if the CH50 results were > 10 U Eq/mL and/or the unbound nomacopan in serum was < 55 ng/mL. Two dose escalations were permitted - an increase from the maintenance dose of 0.30 mg/kg to 0.45 mg/kg with a further increase to 0.60 mg/kg if required. Dose increases were preceded by an ablating dose as determined by age as per Day 1. No patients had a dose increase to 0.60 mg/kg | 0 | 0 | 0 | 0 | 0 | 0 |
| Cytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Device related infection | Infections and infestations | Systematic Assessment |
|
| Generalised oedema | General disorders | Systematic Assessment |
|
| Generalised tonic-clonic seizure | Nervous system disorders | Systematic Assessment |
|
| Hypertension | Vascular disorders | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Multiple organ dysfunction syndrome | General disorders | Systematic Assessment |
|
| Pneumonia parainfluenzae viral | Infections and infestations | Systematic Assessment |
|
| Posterior reversible encephalopathy syndrome | Nervous system disorders | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Thrombotic microangiopathy | Blood and lymphatic system disorders | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Pyrexia | General disorders | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Hypermagnesaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Blood Creatinine Increased | Investigations | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | Systematic Assessment |
|
| Hypernatraemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Blood bicarbonate decreased | Investigations | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypotension | Vascular disorders | Systematic Assessment |
|
Not provided
Not provided
| D000095542 | Cytopenia |