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The study was prematurely terminated by the Sponsor due to operational challenges stemming from the coronavirus disease 2019 (COVID-19) pandemic, treatment limitations, rarity of the disease, and drug supply considerations.
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This study will evaluate the therapeutic effect and safety of adjunctive AKST4290 in subjects with bullous pemphigoid (BP).
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 Subjects who receive rescue therapy will remain in the study until disease control, unless they are withdrawn or withdraw from participation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mometasone furoate + AKST4290 | Experimental | Subjects will receive mometasone furoate concurrently with AKST4290, 400 mg twice daily, until disease control is reached. |
|
| Mometasone furoate + Placebo | Placebo Comparator | Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mometasone furoate | Drug | Topical mometasone furoate |
|
| 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) |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alkahest Medical Monitor | Alkahest, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universitätsklinikum Carl Gustav Carus Dresden Klinik und Poliklinik für Dermatologie | Dresden | 01307 | Germany | |||
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | Mometasone Furoate + Placebo | Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Mometasone Furoate + Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | Baseline to up to 3 weeks (until disease control) |
|
5 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood potassium decreased | Investigations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Head of Communications | Alkahest, Inc. | (650) 801-0474 | info@alkahest.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 15, 2020 | Mar 29, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 10, 2021 | Mar 29, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D010391 | Pemphigoid, Bullous |
| D001327 | Autoimmune Diseases |
| D012871 | Skin Diseases |
| ID | Term |
|---|---|
| D012872 | Skin Diseases, Vesiculobullous |
| D017437 | Skin and Connective Tissue Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000068656 | Mometasone Furoate |
| ID | Term |
|---|---|
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 |
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| AKST4290 | Drug | Oral AKST4290 |
|
| Placebo | Drug | Oral placebo |
|
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. |
| Universitätsklinikum Düsseldorf Klinik für Dermatologie |
| Düsseldorf |
| 40225 |
| Germany |
| Universitätsklinikum Erlangen - Hautklinik | Erlangen | 91054 | Germany |
| Universitätsklinikum Freiburg Klinik für Dermatologie und Venerologie | Freiburg im Breisgau | 79104 | Germany |
| Universitätsklinikum Schleswig-Holstein Klinik für Dermatologie, Allergologie und Venerologie (Hautklinik) Exzellenzzentrum Entzündungsmedizin | Lübeck | 23538 | Germany |
| Universitätsklinikum Magdeburg A.ö.R. Universitätshautklinik | Magdeburg | 39120 | Germany |
| Universitätsmedizin der Johannes Gutenberg-Universität Mainz Hautklinik Clinical Research Center (CRC) | Mainz | 55131 | Germany |
| Universitätsklinikum Würzburg Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie | Würzburg | 97080 | Germany |
Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Secondary | 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 | The Safety Evaluable Set includes all randomized subjects who receive at least 1 dose of the study agent (AKST4290 or placebo) | Posted | Count of Participants | Participants | Baseline to 5 weeks |
|
|
|
| Secondary | 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. | Analysis population includes subjects who achieved disease control with and without rescue therapy. | Posted | Count of Participants | Participants | Baseline to up to 3 weeks (until disease control) |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 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. |
|
|
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| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | 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. |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | 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. |
|
|
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| Secondary | Total Cumulative Steroid Exposure | Total cumulative steroid exposure (cortisol equivalent/kg) by treatment group | 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. | Posted | Mean | Standard Deviation | mg cortisol equivalent/kg | 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. |
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| Secondary | 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. | 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. | Posted | Number | mg cortisol equivalent/kg | 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. |
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| 0 |
| 5 |
| 0 |
| 5 |
| 2 |
| 5 |
| EG001 | Mometasone Furoate + Placebo | Subjects will receive mometasone furoate concurrently with placebo until disease control is reached. Mometasone furoate: Topical mometasone furoate Placebo: Oral placebo | 1 | 1 | 1 | 1 | 0 | 1 |
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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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.
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| TEAE by Severity: Mild |
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| TEAE by Severity: Moderate |
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| TEAE by Severity: Severe |
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| Time (Days) to Disease Control: 15 |
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| Time (Days) to Disease Control: 16 |
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| Time (Days) to Disease Control: 22 |
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| Time (Days) to Rescue Therapy 9 |
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| Total BPDAI Skin Urticarial Score: Baseline |
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| Total BPDAI Skin Urticarial Score: EOT |
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| Total BPDAI Mucosal Activity Score: Baseline |
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| Total BPDAI Mucosal Activity Score: EOT |
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| Total BPDAI Damage Score: Baseline |
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| Total BPDAI Damage Score: EOT |
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| Maximum Daily Steroid Dose Occurred: Day 8 |
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| Maximum Daily Steroid Dose Occurred: Day 11 |
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