Trial Outcomes & Findings for A Study to Assess the Therapeutic Effect and Safety of Adjunctive AKST4290 in Subjects With Bullous Pemphigoid (NCT NCT04499235)

NCT ID: NCT04499235

Last Updated: 2023-09-14

Results Overview

Disease control is defined as ≤ 3 new blisters/eczematous lesions/urticarial plaques/day and healing of existing blisters/eczematous lesions/urticarial plaques without requiring rescue therapy.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 6 participants
• Primary outcome timeframe: Baseline to up to 3 weeks (until disease control)
• Results posted on: 2023-09-14

Participant Flow

Enrolled participants per the protocol are participants who are randomized to mometasone furoate + AKST4290 or mometasone furoate + placebo. Subjects screened but not randomized are not reflected in Participant Flow. The study enrolled 6 subjects of the planned 30 subjects before study prematurely terminated by the Sponsor.

Participant milestones

Measure	Mometasone Furoate + AKST4290 Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. Mometasone furoate: Topical mometasone furoate AKST4290: Oral AKST4290	Mometasone Furoate + Placebo Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo
Overall Study STARTED	5	1
Overall Study COMPLETED	5	1
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Assess the Therapeutic Effect and Safety of Adjunctive AKST4290 in Subjects With Bullous Pemphigoid

Baseline characteristics by cohort

Measure	Mometasone Furoate + AKST4290 n=5 Participants Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. Mometasone furoate: Topical mometasone furoate AKST4290: Oral AKST4290	Mometasone Furoate + Placebo n=1 Participants Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo	Total n=6 Participants Total of all reporting groups
Age, Continuous	66 years STANDARD_DEVIATION 7.78 • n=5 Participants	60 years n=7 Participants	65 years STANDARD_DEVIATION 7.38 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to up to 3 weeks (until disease control)

Disease control is defined as ≤ 3 new blisters/eczematous lesions/urticarial plaques/day and healing of existing blisters/eczematous lesions/urticarial plaques without requiring rescue therapy.

Outcome measures

Measure	Mometasone Furoate + AKST4290 n=5 Participants Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. Mometasone furoate: Topical mometasone furoate AKST4290: Oral AKST4290	Mometasone Furoate + Placebo n=1 Participants Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo
The Percentage of Subjects Who Achieve Disease Control Without Rescue Therapy	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline to 5 weeks

Population: The Safety Evaluable Set includes all randomized subjects who receive at least 1 dose of the study agent (AKST4290 or placebo)

Treatment-emergent AEs summarized by MedDRA coding terms; separate tabulations produced for incidence, seriousness and severity of AEs

Outcome measures

Measure	Mometasone Furoate + AKST4290 n=5 Participants Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. Mometasone furoate: Topical mometasone furoate AKST4290: Oral AKST4290	Mometasone Furoate + Placebo n=1 Participants Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo
Number of Participants With TEAEs, Assessed by Seriousness and Severity Subjects Reporting at Least One TEAE	2 Participants	1 Participants
Number of Participants With TEAEs, Assessed by Seriousness and Severity Subjects Reporting at Least One Serious TEAE	0 Participants	1 Participants
Number of Participants With TEAEs, Assessed by Seriousness and Severity TEAE by Severity: Mild	2 Participants	0 Participants
Number of Participants With TEAEs, Assessed by Seriousness and Severity TEAE by Severity: Moderate	0 Participants	0 Participants
Number of Participants With TEAEs, Assessed by Seriousness and Severity TEAE by Severity: Severe	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline to up to 3 weeks (until disease control)

Population: Analysis population includes subjects who achieved disease control with and without rescue therapy.

Time to disease control by treatment day/week. The time to disease control is calculated as the date of disease control minus Date of Visit 2 (Baseline (Day 1)) plus 1.

Outcome measures

Measure	Mometasone Furoate + AKST4290 n=5 Participants Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. Mometasone furoate: Topical mometasone furoate AKST4290: Oral AKST4290	Mometasone Furoate + Placebo n=1 Participants Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo
Time to Disease Control Time (Days) to Disease Control: 8	1 Participants	0 Participants
Time to Disease Control Time (Days) to Disease Control: 11	2 Participants	0 Participants
Time to Disease Control Time (Days) to Disease Control: 15	0 Participants	1 Participants
Time to Disease Control Time (Days) to Disease Control: 16	1 Participants	0 Participants
Time to Disease Control Time (Days) to Disease Control: 22	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to up to 3 weeks (EOT). EOT occurs at disease control (assessed every day from Week 1/Day 7 up to Week 3/Day 21 +/- 2 days) or at Week 3/Day 21 +/- 2 days when the subject is discontinued from treatment due to not reaching disease control.

Time to rescue therapy by treatment day/week. The time to rescue therapy is calculated as the start date of the first rescue therapy minus Date of Visit 2 (Baseline (Day 1)) plus 1.

Outcome measures

Measure	Mometasone Furoate + AKST4290 n=5 Participants Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. Mometasone furoate: Topical mometasone furoate AKST4290: Oral AKST4290	Mometasone Furoate + Placebo n=1 Participants Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo
Time to Rescue Therapy Time (Days) to Rescue Therapy: 4	1 Participants	0 Participants
Time to Rescue Therapy Time (Days) to Rescue Therapy 8	1 Participants	0 Participants
Time to Rescue Therapy Time (Days) to Rescue Therapy 9	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to up to 3 weeks (EOT). EOT occurs at disease control (assessed every day from Week 1/Day 7 up to Week 3/Day 21 +/- 2 days) or at Week 3/Day 21 +/- 2 days when the subject is discontinued from treatment due to not reaching disease control.

Change from baseline in BPDAI score at End of Treatment (EOT). Subscales for the BPDAI include the skin blister score (range 0-120), skin urticarial score (range 0-120), mucosal activity score (range 0-120), and damage score (range 0-12). Higher scores indicate greater disease activity or damage.

Outcome measures

Measure	Mometasone Furoate + AKST4290 n=5 Participants Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. Mometasone furoate: Topical mometasone furoate AKST4290: Oral AKST4290	Mometasone Furoate + Placebo n=1 Participants Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo
The Bullous Pemphigoid Disease Area Index (BPDAI) Score Total BPDAI Mucosal Activity Score: EOT	1.6 score on a scale Standard Deviation 3.58	0 score on a scale
The Bullous Pemphigoid Disease Area Index (BPDAI) Score Total BPDAI Skin Blister Score: Baseline	15 score on a scale Standard Deviation 12.83	13.0 score on a scale
The Bullous Pemphigoid Disease Area Index (BPDAI) Score Total BPDAI Skin Blister Score: EOT	7.4 score on a scale Standard Deviation 7.02	8.0 score on a scale
The Bullous Pemphigoid Disease Area Index (BPDAI) Score Total BPDAI Skin Urticarial Score: Baseline	16.4 score on a scale Standard Deviation 9.15	14.0 score on a scale
The Bullous Pemphigoid Disease Area Index (BPDAI) Score Total BPDAI Skin Urticarial Score: EOT	9.2 score on a scale Standard Deviation 6.38	12.0 score on a scale
The Bullous Pemphigoid Disease Area Index (BPDAI) Score Total BPDAI Mucosal Activity Score: Baseline	3.4 score on a scale Standard Deviation 7.60	0 score on a scale
The Bullous Pemphigoid Disease Area Index (BPDAI) Score Total BPDAI Damage Score: Baseline	5.0 score on a scale Standard Deviation 4.18	9.0 score on a scale
The Bullous Pemphigoid Disease Area Index (BPDAI) Score Total BPDAI Damage Score: EOT	5.0 score on a scale Standard Deviation 3.81	8.0 score on a scale

SECONDARY outcome

Timeframe: Baseline to up to 3 weeks (EOT). EOT occurs at disease control (assessed every day from Week 1/Day 7 up to Week 3/Day 21 +/- 2 days) or at Week 3/Day 21 +/- 2 days when the subject is discontinued from treatment due to not reaching disease control.

Change from baseline in pruritus as evaluated by the BPDAI-VAS at End of Treatment (EOT). EOT occurs at disease control (up to 3 weeks) or at Week 3 when the subject is discontinued from treatment due to not reaching disease control. Scores for the BPDAI-VAS can range from 0 to 30, with higher scores indicating a worse condition.

Outcome measures

Measure	Mometasone Furoate + AKST4290 n=5 Participants Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. Mometasone furoate: Topical mometasone furoate AKST4290: Oral AKST4290	Mometasone Furoate + Placebo n=1 Participants Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo
The Bullous Pemphigoid Disease Area Index Visual Analog Scale (BPDAI-VAS) BPDAI-VAS Baseline	19.4 score on a scale Standard Deviation 5.68	15.0 score on a scale
The Bullous Pemphigoid Disease Area Index Visual Analog Scale (BPDAI-VAS) BPDAI-VAS EOT	9.2 score on a scale Standard Deviation 3.42	4.0 score on a scale

SECONDARY outcome

Timeframe: Baseline to up to 3 weeks (EOT). EOT occurs at disease control (assessed every day from Week 1/Day 7 up to Week 3/Day 21 +/- 2 days) or at Week 3/Day 21 +/- 2 days when the subject is discontinued from treatment due to not reaching disease control.

Population: Total cumulative steroid exposure is calculated based on oral route treatment from Day 1 to EOT/disease control. Subjects with no oral route treatment were excluded from analysis.

Total cumulative steroid exposure (cortisol equivalent/kg) by treatment group

Outcome measures

Measure	Mometasone Furoate + AKST4290 n=3 Participants Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. Mometasone furoate: Topical mometasone furoate AKST4290: Oral AKST4290	Mometasone Furoate + Placebo Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo
Total Cumulative Steroid Exposure	260 mg cortisol equivalent/kg Standard Deviation 210	—

SECONDARY outcome

Timeframe: Baseline to up to 3 weeks (EOT). EOT occurs at disease control (assessed every day from Week 1/Day 7 up to Week 3/Day 21 +/- 2 days) or at Week 3/Day 21 +/- 2 days when the subject is discontinued from treatment due to not reaching disease control.

Population: The analysis population includes subjects who received systemic steroids. In the AKST4290 group, 3 subjects received systemic steroids. In the Placebo group, the single subject did not have systemic steroid exposure.

Evaluation of maximum daily steroid dose at baseline, by treatment week, and at disease control. Study Day 1 is defined as the initiation of study treatment. 1 mg/kg prednisolon(e) = 5 mg/kg cortisone.

Outcome measures

Measure	Mometasone Furoate + AKST4290 n=3 Participants Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. Mometasone furoate: Topical mometasone furoate AKST4290: Oral AKST4290	Mometasone Furoate + Placebo Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo
Maximum Daily Steroid Dose Maximum Daily Steroid Dose Occurred: Day 4	175 mg cortisol equivalent/kg	—
Maximum Daily Steroid Dose Maximum Daily Steroid Dose Occurred: Day 8	150 mg cortisol equivalent/kg	—
Maximum Daily Steroid Dose Maximum Daily Steroid Dose Occurred: Day 11	150 mg cortisol equivalent/kg	—

Adverse Events

Mometasone Furoate + AKST4290

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Mometasone Furoate + Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Measure	Mometasone Furoate + AKST4290 n=5 participants at risk Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. Mometasone furoate: Topical mometasone furoate AKST4290: Oral AKST4290	Mometasone Furoate + Placebo n=1 participants at risk Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo
Infections and infestations COVID-19	0.00% 0/5 • 5 weeks	100.0% 1/1 • Number of events 1 • 5 weeks

Other adverse events

Measure	Mometasone Furoate + AKST4290 n=5 participants at risk Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. Mometasone furoate: Topical mometasone furoate AKST4290: Oral AKST4290	Mometasone Furoate + Placebo n=1 participants at risk Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo
Investigations Blood potassium decreased	20.0% 1/5 • Number of events 1 • 5 weeks	0.00% 0/1 • 5 weeks
Skin and subcutaneous tissue disorders Rash	20.0% 1/5 • Number of events 1 • 5 weeks	0.00% 0/1 • 5 weeks

Additional Information

Head of Communications

Alkahest, Inc.

Phone: (650) 801-0474

Email: info@alkahest.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Clinical Trial Agreement contains language that restricts the PI from discussing or publishing Sponsor confidential and/or proprietary information. The embargo period may be extended by mutual agreement of the Sponsor and PI.
• Publication restrictions are in place

Restriction type: OTHER