Clinical Trial Results:
Multicentre Study of Nomacopan in Paediatric Haematopoietic Stem-Cell Transplant associated Thrombotic Microangiopathy
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Summary
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EudraCT number |
2020-000086-17 |
Trial protocol |
GB PL |
Global end of trial date |
15 May 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
16 May 2025
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First version publication date |
16 May 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AK901
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04784455 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Akari Therapeutic Plc.
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Sponsor organisation address |
75-76 Wimpole Street, London, United Kingdom, W1G 9RT
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Public contact |
Information Desk, Akari Therapeutics Plc, +44 2080040261, info@akaritx.com
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Scientific contact |
Information Desk, Akari Therapeutics Plc, +44 2080040261, info@akaritx.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 Nov 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 May 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
15 May 2024
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
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 safety and efficacy trial.
The trial was closed after completion of Part A and did not proceed to Part B.
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Protection of trial subjects |
Where possible study specific blood samples were taken at the same time as routine sampling for clinical care.
The volume of blood taken from patients was monitored very carefully. Sites monitored and recorded the blood volume taken for each patient to ensure daily blood samples was not greater than 3% of the patient's total blood volume. Further, the "Day 3" and "Day 7 - 6 hour" blood samples were not taken in the youngest cohort (≥ 0.5 to < 2 years).
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Background therapy |
No background therapy was specified for the study. Any background treatment was as prescribed by the treating clinician (except eculizumab or any other complement blocker therapy - which were trial exclusion criteria) | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
24 Jul 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 9
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Country: Number of subjects enrolled |
United States: 1
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Worldwide total number of subjects |
10
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
1
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Children (2-11 years) |
5
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Adolescents (12-17 years) |
4
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
AK901 was open to recruitment from 24 July 2020 to 15 May 2024. The study was open in 4 UK sites, 4 US sites and 1 Polish site. | ||||||||||||
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Pre-assignment
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Screening details |
Paediatric patients who underwent allogeneic or autologous haematopoietic stem cell transplantation (HSCT) and within a year developed thrombotic microangiopathy (HSCT-TMA) with elevated complement activity and proteinuria. The maximum period between screening and starting nomacopan was 21 days, but treatment was started as soon as possible. | ||||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Nomacopan | ||||||||||||
Arm description |
Patients were administered nomacopan subcutaneously, twice daily for a maximum of 24 weeks | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Nomacopan
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Investigational medicinal product code |
PRD4020816
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Other name |
Coversin
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Pharmaceutical forms |
Powder and solution for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Patients were given an ablating dose on Day 1, 12 hours apart which was determined by the child's weight on Day1:
Ablating Dose:
- 0.5 to < 2 years =1.7 mg/kg
- 2 to < 9 years =1.3 mg/kg
- 9 to < 18 years =1.0 mg/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 Day2 until the end of treatment was 0.30 mg/kg for all 3 age groups.
If required, from pre-dose Day 7onwards, a dose escalation was permitted if the CH50 results were > 10U 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.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
Patients treated with nomacopan | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Nomacopan
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Reporting group description |
Patients were administered nomacopan subcutaneously, twice daily for a maximum of 24 weeks | ||
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End point title |
RBC transfusion independence for ≥ 28 Days immediately prior to any scheduled clinical visit up to Week 24 or Urine Protein Creatinine Ratio (UPCR) ≤ 2 mg/mg maintained over ≥ 28 Days immediately prior to any scheduled clinical visit up to Week 24 [1] | ||||||||||
End point description |
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 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 endpoints.
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End point type |
Primary
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End point timeframe |
24 Weeks
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to the early termination of the study only descriptive primary and secondary efficacy data are presented. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Normalisation of Lab Parameters | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
24 Weeks
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Platelet transfusion independence for ≥ 28 Days immediately prior to any scheduled clinical visit up to Week 24 | ||||||||
End point description |
Platelet Transfusion Independence for ≥ 28 Days Immediately Prior to any Scheduled Clinical Visit up to Week 24.
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 endpoints.
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End point type |
Secondary
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End point timeframe |
24 Weeks
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From the time of consent until end of study (maximum 2 year follow-up)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27
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Reporting groups
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Reporting group title |
Treated patients
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Date |
Amendment |
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02 Jun 2021 |
- sC5b-9 samples were listed as serum instead of plasma, and samples to be analysed centrally rather than locally or centrally
- PK samples were listed as plasma instead of serum
- Inclusion of urine pregnancy testing at sites that are unable to perform serum pregnancy testing
- The 12h samples can be taken at 9 hours if logistical reasons prevent sampling and processing at 12 hours
- CH50 and PK samples not required for patients in the youngest cohort on Day 3, Day 7 - 6h, and Week 4 - 6 hours to minimise the blood draw volume
- Haematology parameters updated to include lymphocytes, monocytes, basophils, and eosinophils
- Clarification that LTB4 will be measured in a 24-hour urine sample |
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10 Nov 2021 |
- Inclusion - time from HSCT to TMA diagnosis increased from 100 days to a year
- Exclusion - time to initiate nomacopan increased from 14 days to 21 days
- Section regarding previous clinical exposure and experience to nomacopan updated
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Part A of the trial was exploratory with a small number of subjects. Due to early closure only 2 of 6 patients alive at Week 24 were followed up at 1 and 2 years. The trial was closed for business reasons unrelated to safety in this or other trials. | |||
