Acne Vulgaris
Conditions
Keywords
acne vulgaris
Brief summary
This is a Phase 1/2a study. The purpose of Phase 1 was to evaluate the safety and tolerability of DRM01B Topical Gel in 6 healthy volunteers. The purpose of Phase 2a was to assess the safety, tolerability and preliminary efficacy of DRM01B Topical Gel compared to vehicle in subjects with acne vulgaris on the face.
Interventions
DRUGOlumacostat Glasaretil Gel, 7.5%
Gel containing Olumacostat Glasaretil
Vehicle (placebo) gel
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
Yes
Inclusion criteria
Phase 1 Inclusion Criteria 1. Signed informed consent 2. Willing to comply with the requirements of the protocol 3. Males or non-pregnant, non-lactating females 4. Age ≥ 18 years 5. Was in good health and free from any clinically significant disease, as determined by the investigator 6. If female and of childbearing potential, was willing to use an accepted method of birth control during study participation and for 30 days after the last application of study drug. Females were considered to be of childbearing potential unless they had been surgically sterilized (hysterectomy, bilateral oophorectomy, tubal ligation), had been diagnosed as infertile, had a same-sex partner or vasectomized male partner, were postmenopausal for at least 1 year, or were abstinent. Acceptable methods of birth control were defined as: abstinence, oral contraceptives, contraceptive patches/implants; Depo-Provera®, double barrier methods (e.g., condom and spermicide) or an intrauterine device (IUD). The birth control method must have been stable/unchanged for 30 days prior to baseline. 7. If male, was vasectomized or agreed to use an accepted method of birth control with female partner during study participation and for 30 days after the last application of study drug. Phase 1
Exclusion criteria
1. Females who were pregnant, planning to become pregnant during the course of the study, or were breast-feeding 2. Had a known hypersensitivity to DRM01B or its excipients 3. Had any skin condition that may have interfered with the safety evaluations during the study 4. Had a clinical chemistry or hematology laboratory value at screening that was considered clinically significant, in the opinion of the investigator 5. Participated in an investigational drug study within 30 days prior to screening 6. Were considered a poor medical risk because of other systemic diseases or active uncontrolled infections, in the opinion of the investigator. Any other condition which, in the judgment of the investigator, would put the subject at unacceptable risk for participation in the study. Phase 2a Inclusion Criteria 1. Signed informed consent 2. Willing to comply with the requirements of the protocol 3. Male or non-pregnant, non-lactating females 4. Age ≥ 18 years 5. If female and of childbearing potential, was willing to use an accepted method of birth control during study participation and for 30 days after the last study drug application. Females were considered to be of childbearing potential unless surgically sterilized (hysterectomy, bilateral oophorectomy, tubal ligation), had been diagnosed as infertile, had same sex partner or vasectomized male partner, or were postmenopausal for at least 1 year. Acceptable methods of birth control were defined as: abstinence, oral contraceptives, contraceptive patches/implants; Depo-Provera®, double barrier methods (e.g., condom and spermicide) or an IUD. The birth control method must have been stable/unchanged for 12 weeks prior to baseline and must have remained unchanged during study participation. 6. If male, was vasectomized or agreed to use an accepted method of birth control with female partner during study participation and for 30 days after the last study drug application. 7. Subjects were in good health and free from any disease that, in the opinion of the investigator, would have put the subject at risk during participation in the study. 8. Clinical diagnosis of facial acne vulgaris defined as: * At least 20 inflammatory lesions * At least 20 noninflammatory lesions * IGA of 3 or greater 9. Willing to refrain from using any treatments, other than the investigational product, including antibiotics, for acne present on the face. Topical acne treatments that did not have significant or measurable systemic absorption (e.g., benzoyl peroxide, salicylic acid) were allowed for treatment of acne of the back, shoulders, and chest only. Phase 2a
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Absolute Change in Acne Lesion Counts (Inflammatory) From Baseline to Week 12 in Phase 2a | Baseline and Week 12 | Mean absolute change in acne lesion counts (inflammatory) from baseline to Week 12 in Phase 2a |
| Mean Absolute Change in Acne Lesion Counts (Non-inflammatory) From Baseline to Week 12 in Phase 2a | Baseline and Week 12 | Mean absolute change in acne lesion counts (non-inflammatory) from baseline to Week 12 in Phase 2a |
| Percentage of Subjects Who Achieved ≥ 2-grade Improvement in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 in Phase 2a | Baseline and Week 12 | Percentage of subjects who achieved ≥ 2-grade improvement in the investigator global assessment of acne (IGA) from baseline to Week 12 in Phase 2a 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
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Olumacostat Glasaretil Gel, 7.5%, Phase 1 Olumacostat Glasaretil Gel, 7.5%, applied twice daily to the face for 7 days in healthy volunteers | 6 |
| Olumacostat Glasaretil Gel, 7.5%, Phase 2a Olumacostat Glasaretil Gel, 7.5%, applied twice daily to the face for 12 weeks | 53 |
| Olumacostat Glasaretil Gel, Vehicle, Phase 2a Olumacostat Glasaretil Gel, Vehicle, applied twice daily to the face for 12 weeks | 55 |
| Total | 114 |
Baseline characteristics
| Characteristic | Olumacostat Glasaretil Gel, 7.5%, Phase 1 | Olumacostat Glasaretil Gel, 7.5%, Phase 2a | Olumacostat Glasaretil Gel, Vehicle, Phase 2a | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 12 Participants | 12 Participants | 24 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 41 Participants | 43 Participants | 90 Participants |
| Age, Continuous | 40.0 years STANDARD_DEVIATION 11.3 | 23.9 years STANDARD_DEVIATION 6.1 | 26.5 years STANDARD_DEVIATION 9 | 26.0 years STANDARD_DEVIATION 7.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 5 Participants | 3 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 48 Participants | 52 Participants | 106 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fitzpatrick Skin Type Type I | 0 Participants | 3 Participants | 3 Participants | 6 Participants |
| Fitzpatrick Skin Type Type II | 2 Participants | 8 Participants | 14 Participants | 24 Participants |
| Fitzpatrick Skin Type Type III | 3 Participants | 18 Participants | 18 Participants | 39 Participants |
| Fitzpatrick Skin Type Type IV | 1 Participants | 16 Participants | 13 Participants | 30 Participants |
| Fitzpatrick Skin Type Type V | 0 Participants | 3 Participants | 2 Participants | 5 Participants |
| Fitzpatrick Skin Type Type VI | 0 Participants | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 9 Participants | 10 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 6 Participants | 5 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 5 Participants | 33 Participants | 38 Participants | 76 Participants |
| Region of Enrollment Canada | 6 Participants | 53 Participants | 55 Participants | 114 Participants |
| Sex: Female, Male Female | 2 Participants | 33 Participants | 38 Participants | 73 Participants |
| Sex: Female, Male Male | 4 Participants | 20 Participants | 17 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 53 | 0 / 55 |
| other Total, other adverse events | 0 / 6 | 29 / 53 | 17 / 55 |
| serious Total, serious adverse events | 0 / 6 | 0 / 53 | 1 / 55 |
Outcome results
Primary
Mean Absolute Change in Acne Lesion Counts (Inflammatory) From Baseline to Week 12 in Phase 2a
Mean absolute change in acne lesion counts (inflammatory) from baseline to Week 12 in Phase 2a
Time frame: Baseline and Week 12
Population: Intent-to-Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olumacostat Glasaretil Gel, 7.5%, Phase 2a | Mean Absolute Change in Acne Lesion Counts (Inflammatory) From Baseline to Week 12 in Phase 2a | -19.865 Lesions | Standard Error 1.107 |
| Olumacostat Glasaretil Gel, Vehicle, Phase 2a | Mean Absolute Change in Acne Lesion Counts (Inflammatory) From Baseline to Week 12 in Phase 2a | -14.296 Lesions | Standard Error 1.079 |
p-value: 0.0003ANCOVA
Primary
Mean Absolute Change in Acne Lesion Counts (Non-inflammatory) From Baseline to Week 12 in Phase 2a
Mean absolute change in acne lesion counts (non-inflammatory) from baseline to Week 12 in Phase 2a
Time frame: Baseline and Week 12
Population: Intent-to-Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olumacostat Glasaretil Gel, 7.5%, Phase 2a | Mean Absolute Change in Acne Lesion Counts (Non-inflammatory) From Baseline to Week 12 in Phase 2a | -20.131 Lesions | Standard Error 1.902 |
| Olumacostat Glasaretil Gel, Vehicle, Phase 2a | Mean Absolute Change in Acne Lesion Counts (Non-inflammatory) From Baseline to Week 12 in Phase 2a | -12.357 Lesions | Standard Error 1.856 |
p-value: 0.0032ANCOVA
Primary
Percentage of Subjects Who Achieved ≥ 2-grade Improvement in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 in Phase 2a
Percentage of subjects who achieved ≥ 2-grade improvement in the investigator global assessment of acne (IGA) from baseline to Week 12 in Phase 2a 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, 7.5%, Phase 2a | Percentage of Subjects Who Achieved ≥ 2-grade Improvement in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 in Phase 2a | Success | 13 Participants |
| Olumacostat Glasaretil Gel, 7.5%, Phase 2a | Percentage of Subjects Who Achieved ≥ 2-grade Improvement in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 in Phase 2a | Failure | 40 Participants |
| Olumacostat Glasaretil Gel, Vehicle, Phase 2a | Percentage of Subjects Who Achieved ≥ 2-grade Improvement in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 in Phase 2a | Success | 4 Participants |
| Olumacostat Glasaretil Gel, Vehicle, Phase 2a | Percentage of Subjects Who Achieved ≥ 2-grade Improvement in the Investigator Global Assessment of Acne (IGA) From Baseline to Week 12 in Phase 2a | Failure | 51 Participants |
p-value: 0.007Cochran-Mantel-Haenszel