MedDRA version: 20.0 Level: PT Classification code 10043645 Term: Thrombotic microangiopathy System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 21.1 Level: PT Classification code 10063581 Term: Stem cell transplant System Organ Class: 10042613 - Surgical and medical procedures MedDRA version: 22.0 Level: PT Classification code 10067859 Term: Allogenic stem cell transplantation System Organ Class: 10042613 - Surgical and medical procedures MedDRA version: 22.0
Conditions
Interventions
Product Name: Nomacopan
Product Code: rVA576
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: NOMACOPAN
Current Sponsor code: rVA576
Concentration unit: mg milligram(s)
Conc
Sponsors
Akari Therapeutics Plc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged = 0.5 and 2 mg/mg (demonstrated on two separate morning samples, at least one day apart) ? elevated LDH (> ULN) ? thrombocytopaenia ( 2 mg/mg (demonstrated on two separate morning samples, at least one day apart), and ? elevated serum C5b-9 (80% or more of ULN for age) 5. Provision of written informed consent. 6. Provision of informed assent Are the trial subjects under 18? yes Number of subjects for this age range: 72 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients weighing less than 5 kg. 2. Patients with a positive direct Coomb's test. 3. Patients who do not receive nomacopan within 14 days of the initial diagnosis of TMA. 4. Patients having an active systemic or organ system bacterial or fungal infection or progressive severe infection (including unresolved or untreated Neisseria meningitidis infection and E. coli Shiga toxin) at the time of diagnosis of the TMA. 5. Grade 4 Acute GVHD (as per the Glucksberg grading system, see section 18.9). 6. Received eculizumab or any other complement blocker therapy at any time. 7. Known hypersensitivity to the active ingredient or excipients 8. Patients who are pregnant and/or breastfeeding. All females of childbearing potential require a negative pregnancy test at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A (7 patients aged = 0.5 to < 18 years, in three age range cohorts) Dose algorithm confirmation: ? To confirm the effective dose of nomacopan for the ablation of terminal complement activity. The data derived from Part A of the trial will be used together with existing data for PK/PD simulation modelling to define an age-based dosing regimen to completely control terminal complement activity in paediatric patients treated with nomacopan in Part B ;Secondary Objective: Efficacy: To determine that the age-based dosing regimen defined in Part A can completely control complement activity in paediatric patients treated with nomacopan. Safety: To evaluate safety and tolerability of nomacopan ;Primary end point(s): Composite Primary Endpoint ? RBC transfusion independence for = 28 days immediately prior to any scheduled clinical visit up to Week 24 or Urine protein creatinine ratio = 2 mg/mg for = 28 days immediately prior to any scheduled clinical visit up to Week 24 ;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Secondary Efficacy Endpoints ?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† for = 28 days. ? Serum sC5b-9 = ULN ? Lactate dehydrogenase (LDH) =ULN ?Normalization of haptoglobin -Secondary Safety Endpoints ? Safety and tolerability of nomacopan ;Timepoint(s) of evaluation of this end point: At 24 weeks and the sC5b-9, LDH and haptoglobin will be measured at the last efficacy assessment in the trial before nomacopan treatment is stopped. | — |
Countries
Italy, Poland, United Kingdom, United States
Contacts
Public ContactDr James Fettiplace MBBS
Akari Therapeutics Plc
Outcome results
None listed