Pemphigoid, Bullous
Conditions
Keywords
Autoimmune disease, Skin disease, Vesiculobullous
Brief summary
This study will evaluate the therapeutic effect and safety of adjunctive AKST4290 in subjects with bullous pemphigoid (BP).
Detailed description
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 Subjects who receive rescue therapy will remain in the study until disease control, unless they are withdrawn or withdraw from participation.
Interventions
Sponsors
Alkahest, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
60 Years to 95 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Subjects Who Achieve Disease Control Without Rescue Therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Disease Control | Baseline to up to 3 weeks (until 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. |
| Time to Rescue Therapy | 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. |
| The Bullous Pemphigoid Disease Area Index (BPDAI) Score | 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. |
| Number of Participants With TEAEs, Assessed by Seriousness and Severity | Baseline to 5 weeks | Treatment-emergent AEs summarized by MedDRA coding terms; separate tabulations produced for incidence, seriousness and severity of AEs |
| Total Cumulative Steroid Exposure | 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 (cortisol equivalent/kg) by treatment group |
| Maximum Daily Steroid Dose | 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. | 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 Bullous Pemphigoid Disease Area Index Visual Analog Scale (BPDAI-VAS) | 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. |
Countries
Germany
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 5 |
| 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 |
| Total | 6 |
Baseline characteristics
| Characteristic | Mometasone Furoate + Placebo | Total | Mometasone Furoate + AKST4290 |
|---|---|---|---|
| Age, Continuous | 60 years | 65 years STANDARD_DEVIATION 7.38 | 66 years STANDARD_DEVIATION 7.78 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 6 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 6 Participants | 5 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 1 / 1 |
| other Total, other adverse events | 2 / 5 | 0 / 1 |
| serious Total, serious adverse events | 0 / 5 | 1 / 1 |
Outcome results
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.
Time frame: Baseline to up to 3 weeks (until disease control)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mometasone Furoate + AKST4290 | The Percentage of Subjects Who Achieve Disease Control Without Rescue Therapy | 2 Participants |
| Mometasone Furoate + Placebo | The Percentage of Subjects Who Achieve Disease Control Without Rescue Therapy | 1 Participants |
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mometasone Furoate + AKST4290 | Maximum Daily Steroid Dose | Maximum Daily Steroid Dose Occurred: Day 4 | 175 mg cortisol equivalent/kg |
| Mometasone Furoate + AKST4290 | Maximum Daily Steroid Dose | Maximum Daily Steroid Dose Occurred: Day 8 | 150 mg cortisol equivalent/kg |
| Mometasone Furoate + AKST4290 | Maximum Daily Steroid Dose | Maximum Daily Steroid Dose Occurred: Day 11 | 150 mg cortisol equivalent/kg |
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
Time frame: 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)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mometasone Furoate + AKST4290 | Number of Participants With TEAEs, Assessed by Seriousness and Severity | Subjects Reporting at Least One Serious TEAE | 0 Participants |
| Mometasone Furoate + AKST4290 | Number of Participants With TEAEs, Assessed by Seriousness and Severity | TEAE by Severity: Moderate | 0 Participants |
| Mometasone Furoate + AKST4290 | Number of Participants With TEAEs, Assessed by Seriousness and Severity | TEAE by Severity: Mild | 2 Participants |
| Mometasone Furoate + AKST4290 | Number of Participants With TEAEs, Assessed by Seriousness and Severity | TEAE by Severity: Severe | 0 Participants |
| Mometasone Furoate + AKST4290 | Number of Participants With TEAEs, Assessed by Seriousness and Severity | Subjects Reporting at Least One TEAE | 2 Participants |
| Mometasone Furoate + Placebo | Number of Participants With TEAEs, Assessed by Seriousness and Severity | TEAE by Severity: Severe | 1 Participants |
| Mometasone Furoate + Placebo | Number of Participants With TEAEs, Assessed by Seriousness and Severity | Subjects Reporting at Least One TEAE | 1 Participants |
| Mometasone Furoate + Placebo | Number of Participants With TEAEs, Assessed by Seriousness and Severity | Subjects Reporting at Least One Serious TEAE | 1 Participants |
| Mometasone Furoate + Placebo | Number of Participants With TEAEs, Assessed by Seriousness and Severity | TEAE by Severity: Mild | 0 Participants |
| Mometasone Furoate + Placebo | Number of Participants With TEAEs, Assessed by Seriousness and Severity | TEAE by Severity: Moderate | 0 Participants |
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mometasone Furoate + AKST4290 | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Skin Blister Score: Baseline | 15 score on a scale | Standard Deviation 12.83 |
| Mometasone Furoate + AKST4290 | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Skin Blister Score: EOT | 7.4 score on a scale | Standard Deviation 7.02 |
| Mometasone Furoate + AKST4290 | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Skin Urticarial Score: Baseline | 16.4 score on a scale | Standard Deviation 9.15 |
| Mometasone Furoate + AKST4290 | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Skin Urticarial Score: EOT | 9.2 score on a scale | Standard Deviation 6.38 |
| Mometasone Furoate + AKST4290 | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Mucosal Activity Score: Baseline | 3.4 score on a scale | Standard Deviation 7.6 |
| Mometasone Furoate + AKST4290 | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Mucosal Activity Score: EOT | 1.6 score on a scale | Standard Deviation 3.58 |
| Mometasone Furoate + AKST4290 | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Damage Score: Baseline | 5.0 score on a scale | Standard Deviation 4.18 |
| Mometasone Furoate + AKST4290 | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Damage Score: EOT | 5.0 score on a scale | Standard Deviation 3.81 |
| Mometasone Furoate + Placebo | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Damage Score: EOT | 8.0 score on a scale | — |
| Mometasone Furoate + Placebo | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Skin Blister Score: Baseline | 13.0 score on a scale | — |
| Mometasone Furoate + Placebo | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Mucosal Activity Score: Baseline | 0 score on a scale | — |
| Mometasone Furoate + Placebo | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Skin Blister Score: EOT | 8.0 score on a scale | — |
| Mometasone Furoate + Placebo | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Damage Score: Baseline | 9.0 score on a scale | — |
| Mometasone Furoate + Placebo | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Skin Urticarial Score: Baseline | 14.0 score on a scale | — |
| Mometasone Furoate + Placebo | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Mucosal Activity Score: EOT | 0 score on a scale | — |
| Mometasone Furoate + Placebo | The Bullous Pemphigoid Disease Area Index (BPDAI) Score | Total BPDAI Skin Urticarial Score: EOT | 12.0 score on a scale | — |
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mometasone Furoate + AKST4290 | The Bullous Pemphigoid Disease Area Index Visual Analog Scale (BPDAI-VAS) | BPDAI-VAS Baseline | 19.4 score on a scale | Standard Deviation 5.68 |
| Mometasone Furoate + AKST4290 | The Bullous Pemphigoid Disease Area Index Visual Analog Scale (BPDAI-VAS) | BPDAI-VAS EOT | 9.2 score on a scale | Standard Deviation 3.42 |
| Mometasone Furoate + Placebo | The Bullous Pemphigoid Disease Area Index Visual Analog Scale (BPDAI-VAS) | BPDAI-VAS Baseline | 15.0 score on a scale | — |
| Mometasone Furoate + Placebo | The Bullous Pemphigoid Disease Area Index Visual Analog Scale (BPDAI-VAS) | BPDAI-VAS EOT | 4.0 score on a scale | — |
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.
Time frame: Baseline to up to 3 weeks (until disease control)
Population: Analysis population includes subjects who achieved disease control with and without rescue therapy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mometasone Furoate + AKST4290 | Time to Disease Control | Time (Days) to Disease Control: 11 | 2 Participants |
| Mometasone Furoate + AKST4290 | Time to Disease Control | Time (Days) to Disease Control: 16 | 1 Participants |
| Mometasone Furoate + AKST4290 | Time to Disease Control | Time (Days) to Disease Control: 15 | 0 Participants |
| Mometasone Furoate + AKST4290 | Time to Disease Control | Time (Days) to Disease Control: 22 | 1 Participants |
| Mometasone Furoate + AKST4290 | Time to Disease Control | Time (Days) to Disease Control: 8 | 1 Participants |
| Mometasone Furoate + Placebo | Time to Disease Control | Time (Days) to Disease Control: 22 | 0 Participants |
| Mometasone Furoate + Placebo | Time to Disease Control | Time (Days) to Disease Control: 8 | 0 Participants |
| Mometasone Furoate + Placebo | Time to Disease Control | Time (Days) to Disease Control: 11 | 0 Participants |
| Mometasone Furoate + Placebo | Time to Disease Control | Time (Days) to Disease Control: 15 | 1 Participants |
| Mometasone Furoate + Placebo | Time to Disease Control | Time (Days) to Disease Control: 16 | 0 Participants |
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mometasone Furoate + AKST4290 | Time to Rescue Therapy | Time (Days) to Rescue Therapy 9 | 1 Participants |
| Mometasone Furoate + AKST4290 | Time to Rescue Therapy | Time (Days) to Rescue Therapy: 4 | 1 Participants |
| Mometasone Furoate + AKST4290 | Time to Rescue Therapy | Time (Days) to Rescue Therapy 8 | 1 Participants |
| Mometasone Furoate + Placebo | Time to Rescue Therapy | Time (Days) to Rescue Therapy: 4 | 0 Participants |
| Mometasone Furoate + Placebo | Time to Rescue Therapy | Time (Days) to Rescue Therapy 8 | 0 Participants |
| Mometasone Furoate + Placebo | Time to Rescue Therapy | Time (Days) to Rescue Therapy 9 | 0 Participants |
Secondary
Total Cumulative Steroid Exposure
Total cumulative steroid exposure (cortisol equivalent/kg) by treatment group
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mometasone Furoate + AKST4290 | Total Cumulative Steroid Exposure | 260 mg cortisol equivalent/kg | Standard Deviation 210 |