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

Study Overview
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Brief Summary
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This study will evaluate the therapeutic effect and safety of adjunctive AKST4290 in subjects with bullous pemphigoid (BP).

Detailed Description
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This is a randomized, double-blind, placebo-controlled study to assess the therapeutic effect and safety of adjunctive AKST4290 in subjects with bullous pemphigoid (BP). Subjects will receive topical mometasone furoate cream (MFC) therapy concurrently with study agent (placebo or AKST4290) in an inpatient setting until disease control is reached (duration of inpatient stay is dependent upon individual disease course, but is estimated between 1-3 weeks). Subjects will receive rescue therapy at any time if their clinical condition worsens or if their clinical condition fails to improve by the completion of Week 1 on study treatment, as assessed by the investigator. Rescue therapy will consist of whole-body clobetasol propionate cream (CPC) (15-50g) and/or oral prednisone (0.5 mg/kg per day), as determined by the investigator. Subjects who receive rescue therapy will remain in the study until disease control, unless they are withdrawn or withdraw from participation.

Official Title
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Double-Blind, Randomized, Placebo-Controlled Trial of AKST4290 for Adjunctive Treatment of Mild to Moderate Bullous Pemphigoid

Conditions
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Pemphigoid, Bullous

Intervention / Treatment
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* Drug: Mometasone furoate
* Drug: AKST4290
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of mild to moderate BP at screening. Treatment naïve or initiation of whole-body high potency topical steroid treatment ≤ 7 days of screening (lesion-only treatment for any amount of time with any topical steroids prior to screening is allowed without restriction). Provide a signed and dated informed consent form in accordance with local regulations and/or IRB/IEC guidelines. Exclusion Criteria: Severe BP. Initiation of gliptins and other treatments (e.g., etanercept, sulfasalazine, furosemide, penicillin) that can trigger BP if this treatment was started within 4 weeks prior to screening and is considered possibly related to the onset of BP. Any concomitant medications in the last 3 months prior to screening and assessed by the investigator as possibly related to the development of BP. Planned use of intravenous immunoglobulin or other concomitant treatments for BP (i.e., doxycycline, dapsone) during the study period. Use of systemic immunosuppressants (i.e., mycophenolate, azathioprine, methotrexate) within 4 weeks prior to screening. Treatment with rituximab within 1 year prior to screening. Subjects taking warfarin. Use of systemic steroids (>10 mg prednisone or equivalent/day) within 14 days of first dose of study agent or known diseases (other than BP) that could require the use of systemic steroids within the study period. Clinically relevant abnormal laboratory value at screening, including hematology, blood chemistry, or urinalysis (laboratory testing may be repeated once during the screening phase). Participation in studies of investigational drugs must have been discontinued within 30 days or 5 half lives of the drug (whichever was longer) prior to screening.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mometasone furoate + AKST4290<br>Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. | Drug: Mometasone furoate<br>* Topical mometasone furoate<br>Drug: AKST4290<br>* Oral AKST4290<br>|
| Placebo Comparator: Mometasone furoate + Placebo<br>Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. | Drug: Mometasone furoate<br>* Topical mometasone furoate<br>Drug: Placebo<br>* Oral placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Subjects Who Achieve Disease Control Without Rescue Therapy | 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. | Baseline to up to 3 weeks (until disease control) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With TEAEs, Assessed by Seriousness and Severity | Treatment-emergent AEs summarized by MedDRA coding terms; separate tabulations produced for incidence, seriousness and severity of AEs | Baseline to 5 weeks | 
| Time to Disease Control | 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. | Baseline to up to 3 weeks (until disease control) | 
| Time to Rescue Therapy | 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. | 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. | 
| The Bullous Pemphigoid Disease Area Index (BPDAI) Score | 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. | 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. | 
| The Bullous Pemphigoid Disease Area Index Visual Analog Scale (BPDAI-VAS) | 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. | 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. | 
| Total Cumulative Steroid Exposure | Total cumulative steroid exposure (cortisol equivalent/kg) by treatment group | 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. | 
| Maximum Daily Steroid Dose | 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. | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autoimmune disease, Skin disease, Vesiculobullous