Clinical Trial Results:
Double-Blind, Randomized, Placebo-Controlled Trial of AKST4290 for Adjunctive Treatment of Mild to Moderate Bullous Pemphigoid
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Summary
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EudraCT number |
2019-001059-37 |
Trial protocol |
DE BG |
Global end of trial date |
14 Apr 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
13 May 2022
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First version publication date |
13 May 2022
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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 |
AKST4290-221
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Alkahest, Inc.
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Sponsor organisation address |
125 Shoreway Road, Suite D, San Carlos, United States, CA 94070
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Public contact |
Head of Communications, Alkahest, Inc., +1 650-801-0474, info@alkahest.com
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Scientific contact |
Head of Communications, Alkahest, Inc., +1 650-801-0474, info@alkahest.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 |
16 Feb 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Apr 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Apr 2021
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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 |
To investigate the proportion of subjects who achieved disease control (defined as ≤ 3 new blisters/eczematous lesions/urticarial plaques/day and healing of existing blisters/eczematous lesions/urticarial plaques) without the use of rescue therapy.
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Protection of trial subjects |
Prior to initiation of any study-specific procedures, subjects received a copy of the Informed Consent Form (ICF) that summarized, in non-technical terms, the purpose of the study, the procedures to be carried out, and the potential hazards. The PI or authorized representative explained the nature of the study to the subjects, in non-technical terms, and answered all questions regarding the study. Subjects reviewed, signed, and dated the ICF. Subjects received a copy of the fully signed ICF. The subject was given adequate time to read the ICF and the opportunity to ask questions and consider the statement before signing and dating the form. They were also given a copy of the signed document. No subject entered the study before informed consent or assent with parental consent was obtained. The date the ICF was signed was recorded, and the investigator retained a copy of the signed ICF.
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Background therapy |
AKST4290, 400 mg manufactured by Alkahest, Inc. One batch (lot number 17-0148) was used. AKST4290 is a film-coated pink, oblong tablet manufactured by Alkahest, Inc., with a unit strength of 400 mg. The study agent and matching placebo were delivered to the site, and the drug products were labeled for investigational use only according to applicable local regulatory requirements for clinical studies. | ||
Evidence for comparator |
Placebo. Three batches of Placebo were produced for the study: lot numbers 18-0097, 19-0101, and 19-0175. However, only one batch was administered to a subject (lot 19-0175). | ||
Actual start date of recruitment |
30 Jan 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 |
Bulgaria: 3
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Country: Number of subjects enrolled |
Germany: 3
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Worldwide total number of subjects |
6
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EEA total number of subjects |
6
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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) |
3
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
The planned enrollment was approximately 30 subjects. A total of 6 subjects were enrolled in the study, and all subjects completed the study. All 6 subjects were included in intent-to-treat (ITT) and safety analyses. | |||||||||
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Pre-assignment
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Screening details |
1. Age 60-95 years, inclusive at screening. 2. Clinical diagnosis of mild to moderate BP at screening: • Mild BP was defined as BPDAI ≤ 10 OR < 10% affected body surface • Moderate BP was defined as BPDAI ≥ 10 and ≤ 55 OR 10%-30% affected body surface 3. Treatment naïve or initiation of whole-body high potency topical steroid treatment ≤7 days | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
6 | |||||||||
Number of subjects completed |
6 | |||||||||
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Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor | |||||||||
Blinding implementation details |
To minimize the potential bias at the time of randomization, the study was double-blinded and randomized in a 1:1 ratio (AKST4290:placebo). Randomization codes were generated by a statistician who had no involvement in the study other than generation and maintenance of the randomization codes. When changes to the randomization scheme were implemented on 17 Jun 2020, it was possible to minimize bias by retaining the blind. Blinded staff were only informed about removal of stratification by sites.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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AKST4290 | |||||||||
Arm description |
Subjects received whole-body topical mometasone furoate cream (MFC) therapy (dose and dosing interval dependent upon severity of disease at the time of enrollment, as assessed by the investigator) concurrently with study agent - AKST4290 400 mg twice daily [bid]) in an inpatient setting until disease control was reached (duration of inpatient stay was dependent upon individual disease course – estimated between 1-3 weeks). | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
AKST4290
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Investigational medicinal product code |
AKST4290
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Other name |
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The study agent AKST4290, 400 mg was administered orally bid. During the course of the study, in all the patients, administration of study agent wasperformed at the study site under the direct supervision of the study and/or hospital personnel for documentation of precise administration time.
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Arm title
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Placebo | |||||||||
Arm description |
Subjects received whole-body topical mometasone furoate cream (MFC) therapy (dose and dosing interval dependent upon severity of disease at the time of enrollment, as assessed by the investigator) concurrently with placebo twice daily [bid]) in an inpatient setting until disease control was reached (duration of inpatient stay was dependent upon individual disease course – estimated between 1-3 weeks). | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
Placebo
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Other name |
Placebo
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo was administered orally bid during the course of the study. All study agent and placebo administration were performed at the study site under the direct supervision of the study and/or hospital personnel for documentation of precise administration times.
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Baseline characteristics reporting groups
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Reporting group title |
AKST4290
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Reporting group description |
Subjects received whole-body topical mometasone furoate cream (MFC) therapy (dose and dosing interval dependent upon severity of disease at the time of enrollment, as assessed by the investigator) concurrently with study agent - AKST4290 400 mg twice daily [bid]) in an inpatient setting until disease control was reached (duration of inpatient stay was dependent upon individual disease course – estimated between 1-3 weeks). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects received whole-body topical mometasone furoate cream (MFC) therapy (dose and dosing interval dependent upon severity of disease at the time of enrollment, as assessed by the investigator) concurrently with placebo twice daily [bid]) in an inpatient setting until disease control was reached (duration of inpatient stay was dependent upon individual disease course – estimated between 1-3 weeks). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Primary Efficacy Analysis AKST4290
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The full analysis set (FAS) includes the set of subjects that is as close as possible to the ideal implied by the Intention-to-treat principle. It is derived from the set of all randomized subjects by minimal and justified elimination of subjects.
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Subject analysis set title |
Primary Efficacy Analysis Placebo
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The full analysis set (FAS) includes the set of subjects that is as close as possible to the ideal implied by the Intention-to-treat principle. It is derived from the set of all randomized subjects by minimal and justified elimination of subjects.
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End points reporting groups
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Reporting group title |
AKST4290
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Reporting group description |
Subjects received whole-body topical mometasone furoate cream (MFC) therapy (dose and dosing interval dependent upon severity of disease at the time of enrollment, as assessed by the investigator) concurrently with study agent - AKST4290 400 mg twice daily [bid]) in an inpatient setting until disease control was reached (duration of inpatient stay was dependent upon individual disease course – estimated between 1-3 weeks). | ||
Reporting group title |
Placebo
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Reporting group description |
Subjects received whole-body topical mometasone furoate cream (MFC) therapy (dose and dosing interval dependent upon severity of disease at the time of enrollment, as assessed by the investigator) concurrently with placebo twice daily [bid]) in an inpatient setting until disease control was reached (duration of inpatient stay was dependent upon individual disease course – estimated between 1-3 weeks). | ||
Subject analysis set title |
Primary Efficacy Analysis AKST4290
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The full analysis set (FAS) includes the set of subjects that is as close as possible to the ideal implied by the Intention-to-treat principle. It is derived from the set of all randomized subjects by minimal and justified elimination of subjects.
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Subject analysis set title |
Primary Efficacy Analysis Placebo
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The full analysis set (FAS) includes the set of subjects that is as close as possible to the ideal implied by the Intention-to-treat principle. It is derived from the set of all randomized subjects by minimal and justified elimination of subjects.
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End point title |
achieved disease control without rescue therapy, [1] | ||||||||||||
End point description |
In the AKST4290 group, all 5 (100.0%) subjects achieved disease control. Of these 5 subjects, 3 (60.0%) achieved disease control with rescue therapy, while 2 (40.0%) achieved disease control without rescue therapy. In the Placebo group, the single enrolled subject (100.0%) achieved disease control without rescue therapy. Thus, a greater proportion of subjects in the Placebo group achieved disease control without rescue therapy.
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End point type |
Primary
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End point timeframe |
1 to 3 weeks of inpatient treatment to achieve disease control
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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 limited data-set, formal hypothesis testing was not undertaken. Limited analyses were performed, and descriptive statistics were provided. Analysis datasets of the clinical study protocol included a PP analysis set defined as “a subset of ITT subjects. This analysis set was not utilized in the SAP due to the limited enrollment noted previously and the restriction to descriptive analysis of study endpoints. |
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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 |
All subjects who provided informed consent were evaluated for AEs. All 6 subjects received at least one dose of the study drug and were included in safety analysis. Of 6 subjects, 5 received AKST4290 and 1 received Placebo.
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Adverse event reporting additional description |
Treatment emergent AEs (TEAEs) were summarized by Medical Dictionary for Regulatory Activities (MedDRA) coding terms, and separate tabulations were produced for treatment-related AEs, SAEs, and discontinuations due to AEs.
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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 |
23
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Reporting groups
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Reporting group title |
treatment-emergent AE (TEAEs)
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Reporting group description |
All 6 subjects received at least one dose of the study drug and were included in safety analysis. Of 6 subjects, 5 received AKST4290 and 1 received Placebo. | ||||||||||||||||||||||||
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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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29 May 2019 |
Updates to definitions, assessments, and Inclusion/Exclusion criteria for clarity and accuracy of content; additional rationale for conduct of trial and justification of dose selection |
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31 Jan 2020 |
Updates to study procedures and Inclusion/Exclusion criteria for feasibility and clarity, and content revised to align with updated AKST4290 IB V4.0. |
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15 May 2020 |
Updates to Schedule of Events and study procedures due to removal of follow-on, open-label study; updates to exclusion criteria based on findings from clinical drug-drug interaction study; additional content for clarity on study procedures; optional time points added to improve evaluation of PK. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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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. | |||||||
| Enrolling 6 of the planned 30 subjects making data interpretation difficult. | |||||||
