Acne Vulgaris
Conditions
Brief summary
The objectives of this study are to assess the safety and efficacy DRM01 Topical Gel compared to vehicle in patients with acne vulgaris.
Interventions
DRUGOlumacostat Glasaretil
OTHERVehicle
Sponsors
Dermira, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent. * Male or non-pregnant, non-lactating females. * Age ≥ 18 years. * Clinical diagnosis of facial acne vulgaris defined as: * At least 20 inflammatory lesions * At least 20 non-inflammatory lesions * Investigator Global Assessment of 3 or greater.
Exclusion criteria
* Active cystic acne or acne conglobata, acne fulminans, and secondary acne. * Two or more active nodulocystic lesions. * Screening clinical chemistry or hematology laboratory value that is considered clinically significant, in the opinion of the Investigator. * Abnormal findings on screening ECG, deemed clinically significant, by the Investigator. * Subjects who are actively participating in an experimental therapy study or who have received experimental therapy within 30 days or 5 half-lives (whichever is longer) of the Baseline visit. * Subjects who are a poor medical risk because of other systemic diseases or active uncontrolled infections, in the opinion of the investigator. * Treatment with over-the-counter topical medications for the treatment of acne vulgaris including benzoyl peroxide, topical anti-inflammatory medications, corticosteroids, α-hydroxy/glycolic acid on the face within 2 weeks prior to Baseline. * Treatment with systemic corticosteroids (use of intranasal and inhaled corticosteroids allowed for seasonal allergies and asthma) within 4 weeks prior to Baseline. * Treatment with systemic antibiotics or systemic anti-acne drugs or systemic anti-inflammatory drugs within 4 weeks prior to Baseline. * Prescription topical retinoid use on the face within 4 weeks of Baseline (e.g., tretinoin, tazarotene, adapalene). * Treatment with a new hormonal therapy or dose change to existing hormonal therapy within 12 weeks prior to Baseline. Dose and frequency of use of any hormonal therapy started more than 12 weeks prior to Baseline must remain unchanged throughout the study. Hormonal therapies include, but are not limited to, estrogenic and progestational agents such as birth control pills. * Prior use of androgen receptor blockers (such as spironolactone or flutamide). * Oral retinoid use (e.g., isotretinoin) within 12 months prior to Baseline or vitamin A supplements greater than 10,000 units/day within 6 months of Baseline. * Facial procedures (chemical or laser peel, microdermabrasion, etc.) within the past 8 weeks or during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Absolute Change in Acne Lesion Counts (Inflammatory) From Baseline to Week 12 | Baseline and Week 12 | Mean absolute change in acne lesion counts (inflammatory) from baseline to Week 12 |
| Mean Absolute Change in Acne Lesion Counts (Non-inflammatory) From Baseline to Week 12 | Baseline and Week 12 | Mean absolute change in acne lesion counts (non-inflammatory) from baseline to Week 12 |
| Percentage of Subjects Who Achieved ≥ 2-grade Improvement and a Grade of 0 or 1 in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 | Baseline and Week 12 | Percentage of subjects who achieved ≥ 2-grade improvement and a grade of 0 or 1 in the investigator global assessment of acne (IGA) from baseline to Week 12 Scoring Criteria for Investigator Global Assessment 0 - Clear skin with no inflammatory or noninflammatory lesions 1. \- Almost clear; rare noninflammatory lesions with no more than one small inflammatory lesion 2. \- Mild severity; greater than Grade 1; some noninflammatory lesions with no more than a few inflammatory lesions (papules/pustules only, no nodular lesions) 3. \- Moderate severity; greater than Grade 2; up to many noninflammatory lesions and may have some inflammatory lesions, but no more than one small nodular lesion 4. \- Severe; greater than Grade 3; up to many noninflammatory and inflammatory lesions, but no more than a few nodular lesions |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Olumacostat Glasaretil Gel, Vehicle QD Olumacostat Glasaretil Gel, Vehicle, applied once daily to the face for 12 weeks | 52 |
| Olumacostat Glasaretil Gel, Vehicle BID Olumacostat Glasaretil Gel, Vehicle, applied twice daily to the face for 12 weeks | 50 |
| Olumacostat Glasaretil Gel, 4.0% QD Olumacostat Glasaretil Gel, 4.0%, applied once daily to the face for 12 weeks | 106 |
| Olumacostat Glasaretil Gel, 7.5% QD Olumacostat Glasaretil Gel, 7.5%, applied once daily to the face for 12 weeks | 110 |
| Olumacostat Glasaretil Gel, 7.5% BID Olumacostat Glasaretil Gel, 7.5%, applied twice daily to the face for 12 weeks | 101 |
| Total | 419 |
Baseline characteristics
| Characteristic | Olumacostat Glasaretil Gel, 7.5% QD | Olumacostat Glasaretil Gel, 7.5% BID | Total | Olumacostat Glasaretil Gel, Vehicle QD | Olumacostat Glasaretil Gel, Vehicle BID | Olumacostat Glasaretil Gel, 4.0% QD |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 15 Participants | 14 Participants | 48 Participants | 6 Participants | 3 Participants | 10 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 95 Participants | 87 Participants | 371 Participants | 46 Participants | 47 Participants | 96 Participants |
| Age, Continuous | 26.4 Years STANDARD_DEVIATION 7.96 | 25.9 Years STANDARD_DEVIATION 8.26 | 26.5 Years STANDARD_DEVIATION 7.9 | 26.8 Years STANDARD_DEVIATION 7.65 | 26.7 Years STANDARD_DEVIATION 7.04 | 27 Years STANDARD_DEVIATION 8.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants | 32 Participants | 104 Participants | 12 Participants | 9 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 83 Participants | 68 Participants | 311 Participants | 38 Participants | 41 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 4 Participants | 2 Participants | 0 Participants | 1 Participants |
| Fitzpatrick Skin Type Type I | 12 Participants | 5 Participants | 27 Participants | 1 Participants | 2 Participants | 7 Participants |
| Fitzpatrick Skin Type Type II | 23 Participants | 20 Participants | 76 Participants | 9 Participants | 7 Participants | 17 Participants |
| Fitzpatrick Skin Type Type III | 28 Participants | 30 Participants | 113 Participants | 12 Participants | 17 Participants | 26 Participants |
| Fitzpatrick Skin Type Type IV | 22 Participants | 23 Participants | 98 Participants | 15 Participants | 13 Participants | 25 Participants |
| Fitzpatrick Skin Type Type V | 12 Participants | 13 Participants | 46 Participants | 8 Participants | 4 Participants | 9 Participants |
| Fitzpatrick Skin Type Type VI | 13 Participants | 10 Participants | 59 Participants | 7 Participants | 7 Participants | 22 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 5 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 6 Participants | 19 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 20 Participants | 99 Participants | 16 Participants | 12 Participants | 27 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 15 Participants | 4 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 4 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 75 Participants | 72 Participants | 277 Participants | 28 Participants | 33 Participants | 69 Participants |
| Region of Enrollment Canada | 25 Participants | 24 Participants | 97 Participants | 11 Participants | 12 Participants | 25 Participants |
| Region of Enrollment United States | 85 Participants | 77 Participants | 322 Participants | 41 Participants | 38 Participants | 81 Participants |
| Sex: Female, Male Female | 83 Participants | 79 Participants | 316 Participants | 38 Participants | 39 Participants | 77 Participants |
| Sex: Female, Male Male | 27 Participants | 22 Participants | 103 Participants | 14 Participants | 11 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 50 | 0 / 106 | 0 / 109 | 0 / 101 |
| other Total, other adverse events | 0 / 52 | 0 / 50 | 4 / 106 | 6 / 109 | 7 / 101 |
| serious Total, serious adverse events | 0 / 52 | 0 / 50 | 0 / 106 | 1 / 109 | 0 / 101 |
Outcome results
Primary
Mean Absolute Change in Acne Lesion Counts (Inflammatory) From Baseline to Week 12
Mean absolute change in acne lesion counts (inflammatory) from baseline to Week 12
Time frame: Baseline and Week 12
Population: Intent-to-Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olumacostat Glasaretil Gel, Vehicle QD | Mean Absolute Change in Acne Lesion Counts (Inflammatory) From Baseline to Week 12 | -10.5 Lesions | Standard Deviation 9.79 |
| Olumacostat Glasaretil Gel, Vehicle BID | Mean Absolute Change in Acne Lesion Counts (Inflammatory) From Baseline to Week 12 | -11.0 Lesions | Standard Deviation 9.04 |
| Olumacostat Glasaretil Gel, 4.0% QD | Mean Absolute Change in Acne Lesion Counts (Inflammatory) From Baseline to Week 12 | -14.6 Lesions | Standard Deviation 9.22 |
| Olumacostat Glasaretil Gel, 7.5% QD | Mean Absolute Change in Acne Lesion Counts (Inflammatory) From Baseline to Week 12 | -14.5 Lesions | Standard Deviation 9.49 |
| Olumacostat Glasaretil Gel, 7.5% BID | Mean Absolute Change in Acne Lesion Counts (Inflammatory) From Baseline to Week 12 | -15.0 Lesions | Standard Deviation 9.35 |
p-value: 0.0006Cochran-Mantel-Haenszel
Primary
Mean Absolute Change in Acne Lesion Counts (Non-inflammatory) From Baseline to Week 12
Mean absolute change in acne lesion counts (non-inflammatory) from baseline to Week 12
Time frame: Baseline and Week 12
Population: Intent-To-Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olumacostat Glasaretil Gel, Vehicle QD | Mean Absolute Change in Acne Lesion Counts (Non-inflammatory) From Baseline to Week 12 | -9.3 Lesions | Standard Deviation 15.62 |
| Olumacostat Glasaretil Gel, Vehicle BID | Mean Absolute Change in Acne Lesion Counts (Non-inflammatory) From Baseline to Week 12 | -9.3 Lesions | Standard Deviation 15.07 |
| Olumacostat Glasaretil Gel, 4.0% QD | Mean Absolute Change in Acne Lesion Counts (Non-inflammatory) From Baseline to Week 12 | -15.3 Lesions | Standard Deviation 15.17 |
| Olumacostat Glasaretil Gel, 7.5% QD | Mean Absolute Change in Acne Lesion Counts (Non-inflammatory) From Baseline to Week 12 | -13.4 Lesions | Standard Deviation 15.42 |
| Olumacostat Glasaretil Gel, 7.5% BID | Mean Absolute Change in Acne Lesion Counts (Non-inflammatory) From Baseline to Week 12 | -17.5 Lesions | Standard Deviation 15.15 |
p-value: 0.0002Cochran-Mantel-Haenszel
Primary
Percentage of Subjects Who Achieved ≥ 2-grade Improvement and a Grade of 0 or 1 in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12
Percentage of subjects who achieved ≥ 2-grade improvement and a grade of 0 or 1 in the investigator global assessment of acne (IGA) from baseline to Week 12 Scoring Criteria for Investigator Global Assessment 0 - Clear skin with no inflammatory or noninflammatory lesions 1. \- Almost clear; rare noninflammatory lesions with no more than one small inflammatory lesion 2. \- Mild severity; greater than Grade 1; some noninflammatory lesions with no more than a few inflammatory lesions (papules/pustules only, no nodular lesions) 3. \- Moderate severity; greater than Grade 2; up to many noninflammatory lesions and may have some inflammatory lesions, but no more than one small nodular lesion 4. \- Severe; greater than Grade 3; up to many noninflammatory and inflammatory lesions, but no more than a few nodular lesions
Time frame: Baseline and Week 12
Population: Intent-to-Treat
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Olumacostat Glasaretil Gel, Vehicle QD | Percentage of Subjects Who Achieved ≥ 2-grade Improvement and a Grade of 0 or 1 in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 | Success | 4 Participants |
| Olumacostat Glasaretil Gel, Vehicle QD | Percentage of Subjects Who Achieved ≥ 2-grade Improvement and a Grade of 0 or 1 in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 | Failure | 48 Participants |
| Olumacostat Glasaretil Gel, Vehicle BID | Percentage of Subjects Who Achieved ≥ 2-grade Improvement and a Grade of 0 or 1 in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 | Success | 6 Participants |
| Olumacostat Glasaretil Gel, Vehicle BID | Percentage of Subjects Who Achieved ≥ 2-grade Improvement and a Grade of 0 or 1 in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 | Failure | 44 Participants |
| Olumacostat Glasaretil Gel, 4.0% QD | Percentage of Subjects Who Achieved ≥ 2-grade Improvement and a Grade of 0 or 1 in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 | Success | 23 Participants |
| Olumacostat Glasaretil Gel, 4.0% QD | Percentage of Subjects Who Achieved ≥ 2-grade Improvement and a Grade of 0 or 1 in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 | Failure | 83 Participants |
| Olumacostat Glasaretil Gel, 7.5% QD | Percentage of Subjects Who Achieved ≥ 2-grade Improvement and a Grade of 0 or 1 in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 | Failure | 89 Participants |
| Olumacostat Glasaretil Gel, 7.5% QD | Percentage of Subjects Who Achieved ≥ 2-grade Improvement and a Grade of 0 or 1 in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 | Success | 21 Participants |
| Olumacostat Glasaretil Gel, 7.5% BID | Percentage of Subjects Who Achieved ≥ 2-grade Improvement and a Grade of 0 or 1 in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 | Success | 26 Participants |
| Olumacostat Glasaretil Gel, 7.5% BID | Percentage of Subjects Who Achieved ≥ 2-grade Improvement and a Grade of 0 or 1 in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 | Failure | 75 Participants |
p-value: 0.0055Cochran-Mantel-Haenszel