Clinical Trial Results:
A Phase IIa open label single arm study of safety and efficacy of rVA576 in adult mild to moderate Bullous Pemphigoid subjects
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Summary
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EudraCT number |
2017-002836-18 |
Trial protocol |
NL DE |
Global end of trial date |
29 Apr 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
15 May 2021
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First version publication date |
15 May 2021
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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 |
AK801
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Akari Therapeutics Plc
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Sponsor organisation address |
75-76 Wimpole Street, London, United Kingdom, W1G 9RT
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Public contact |
Chief Scientific Officer, Akari Therapeutics Plc, +44 (0)2080040261, miles.nunn@akaritx.com
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Scientific contact |
Chief Scientific Officer, Akari Therapeutics Plc, +44 (0)2080040261, miles.nunn@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 Dec 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Apr 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Apr 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study is to assess the safety of rVA576 (also known as nomacopan) in adult subjects with mild to moderate BP.
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Protection of trial subjects |
The study was performed in accordance with the current version of the Declaration of Helsinki. The trial was conducted in agreement with the International Conference on Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) E6(R1) which were current at the time of the trial.
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Background therapy |
Topical 0.1% mometasone applied only to lesions up to 30gram/week allowed as maximal background therapy for first 21 days. | ||
Evidence for comparator |
No comparator, single arm. | ||
Actual start date of recruitment |
25 Sep 2018
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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 |
Germany: 5
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Country: Number of subjects enrolled |
Netherlands: 4
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Worldwide total number of subjects |
9
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EEA total number of subjects |
9
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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) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
1
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From 65 to 84 years |
7
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85 years and over |
1
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Recruitment
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Recruitment details |
- | ||||||
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Pre-assignment
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Screening details |
Patients were screened up to 14 days prior to study treatment to confirm eligibility for the study. A total of 13 patients were screened with 4 not being eligible, due to 3 not meeting the exclusion criteria, and 1 not providing consent for the study. | ||||||
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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 |
All patients who received at least one dose of nomacopan. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Nomacopan
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Investigational medicinal product code |
rVA576
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Other name |
coversin, OmCl, VA576
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Pharmaceutical forms |
Powder for suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Day 1 - 60 mg nomacopan administered subcutaneously followed by 30 mg Nomacopan subcutaneously 12 hours later
Days 2-42 - 30 mg nomacopan administered subcutaneously once daily
Note: nomacopan is a lyophilised powder for reconstitution for injection
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
All patients who received at least one dose of nomacopan. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Nomacopan
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Reporting group description |
All patients who received at least one dose of nomacopan. | ||
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End point title |
Proportion of participants reporting CTCAE grade 3,4 and 5 adverse events, related/possibly related to nomacopan during days 1 to day 42 [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 1 (baseline) to Day 42 (end of nomacopan treatment)
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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: Only descriptive statistical were planned and undertaken for evaluation of the primary endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean absolute change in BPDAI activity scores between Baseline (Day 1) and Day 42 | ||||||||||||||||||
End point description |
The BPDAI (Bullous Pemphigoid Disease Area Index) quantifies lesion number and size thresholds. Lesions are rated based on the regions affected. The BPDAI gives additional weighting to areas of the skin primarily affected in BP, such as the limbs, and less emphasis to scalp and face, to better differentiate clinical response in BP.
BPDAI activity scores of <20, 20 - 56 and >57, respectively, are considered to define mild, moderate and severe disease.
The minimum clinically important difference (MCID) in disease symptom improvement is considered a 4 point decrease in BPDAI activity score.
The total BPDAI activity score is the arithmetic sum of three subcomponents - cutaneous blisters/erosions, cutaneous urticaria/erythema, and mucosal blisters/erosions.
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End point type |
Secondary
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End point timeframe |
Day 1 (baseline) to Day 42 (end of nomacopan treatment)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Proportion of patients whose BPDAI activity score decreased by 4 or more points between Baseline (day 1) and Day 42 | ||||||||||||||||
End point description |
The BPDAI (Bullous Pemphigoid Disease Area Index) quantifies lesion number and size thresholds. Lesions are rated based on the regions affected. The BPDAI gives additional weighting to areas of the skin primarily affected in BP, such as the limbs, and less emphasis to scalp and face, to better differentiate clinical response in BP. The minimum clinically important difference (MCID) in disease symptom improvement is considered a 4 point decrease in BPDAI activity score.
The total BPDAI activity score is the arithmetic sum of three subcomponents - cutaneous blisters/erosions, cutaneous urticaria/erythema, and mucosal blisters/erosions.
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End point type |
Secondary
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End point timeframe |
Day 1 (baseline) to Day 42 (end of nomacopan treatment)
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Proportion of patients whose BPDAI activity score increased by 3 or more points between Baseline (Day 1) and Day 42 | ||||||||||||||||
End point description |
The BPDAI (Bullous Pemphigoid Disease Area Index) quantifies lesion number and size thresholds. Lesions are rated based on the regions affected. The BPDAI gives additional weighting to areas of the skin primarily affected in BP, such as the limbs, and less emphasis to scalp and face, to better differentiate clinical response in BP. The minimum clinically important difference (MCID) in disease symptom worsening is considered a 3 point increase in BPDAI activity score.
The total BPDAI activity score is the arithmetic sum of three subcomponents - cutaneous blisters/erosions, cutaneous urticaria/erythema, and mucosal blisters/erosions.
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End point type |
Secondary
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End point timeframe |
Day 1 (baseline) to Day 42 (end of nomacopan treatment)
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Mean absolute change in BPDAI pruritis index between Day 1 (Baseline) and Day 42 | ||||||||
End point description |
The BPDAI-pruritus index component is based on a visual analogue scale (VAS), measuring the severity of itch during the past 24 h (0 - 10), the past week (0 - 10) and the past month (0 - 10) with a total score of 30.
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End point type |
Secondary
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End point timeframe |
Day 1 (baseline) to Day 42 (end of nomacopan treatment)
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean change in Dermatology Life Quality Index (DLQI) between Baseline (Day 1) and Day 42 | ||||||||||||||
End point description |
The DLQI questionnaire was designed to measure how much a persons skin problems have affected their life over the last week. It features 10 items which relate to possible functional, physical,
and psychological repercussions on quality of life. The interpretation of the DLQI scores range from 0-30, and are typically that a score of 0-1 has no effect on the patient’s life, 2-5 has a small effect, 6-10 a moderate effect, and 11-20 a very large effect.
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End point type |
Secondary
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End point timeframe |
Day 1 (baseline) to Day 42 (end of nomacopan treatment)
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Mean change in treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) between Baseline (Day 1) and Day 42 | ||||||||||||||
End point description |
The TABQOL questionnaire was designed to measure the degree of impact on quality of life attributable to the effects of treatment. It features 17 items which relate to possible functional, physical, psychological, and financial repercussions on quality of life. Each item is scored from 0 to 3 points, with higher scores denoting poorer quality of life. The sum of these scores gives the total TABQOL score ranging from 0 to 51.
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End point type |
Secondary
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End point timeframe |
Day 1 (baseline) to Day 42 (end of nomacopan treatment)
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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 |
Day 1 (Baseline) to Day 72 (follow up visit)
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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 |
22.0
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Reporting groups
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Reporting group title |
Nomacopan
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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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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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16 Aug 2018 |
Protocol amendment 4 - To allow patients help with dosing at home, if required.
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09 May 2019 |
Protocol amendment 5 -To allow enrolment of patients receiving systemic treatment for the current episode of BP, provided current treatment was stopped before Day 1.
- Change of exclusion criterion from ‘oral’ steroids to ‘systemic’ steroids.
- To allow patient visits to be conducted at home by suitable staff, to decrease patient burden.
- Inclusion Criteria: Clarification added for patients with disability.
- Addition of disease control assessment at Baseline, any unscheduled and follow-up visits.
- Addition of global BPDAI and Visual Analogue Pruritus assessments at follow-up visit.
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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. | |||
| None reported | |||
