Acne Vulgaris
Conditions
Brief summary
To assess the efficacy of S6G5T-3 compared to its vehicle when applied once daily for 12 weeks in participants with acne vulgaris.
Detailed description
In this Phase 3, multi-center, double-blind, randomized, vehicle-controlled, parallel-group pivotal study, participants will be admitted only after a written informed consent has been obtained and after all inclusion/exclusion criteria have been met. Male and female participants at least 9 years of age with facial acne vulgaris will be eligible for enrollment for daily treatment with S6G5T-3 or its vehicle S6G5T-8, for 12 weeks.
Sponsors
Sol-Gel Technologies, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
9 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participant must sign an Institutional Review Board (IRB) approved written informed consent for this study. 2. Male and female 9 years of age and older. 3. Have 2 or fewer cysts or nodules.
Exclusion criteria
1. More than 2 acne nodules or cysts (defined as an inflammatory lesion greater than or equal to 5 millimeter \[mm\] in diameter). 2. Acne conglobata, acne fulminans and secondary acne (for example, chloracne, drug-induced acne). 3. History of blood dyscrasia (for example, leukemia, haemophilia, sickle cell anemia, multiple myeloma). 4. Underlying disease that requires the use of interfering topical or systemic therapy. 5. Other dermatological conditions that require the use of interfering topical or systemic therapy or that might interfere with study assessments such as, but not limited to, atopic dermatitis, perioral dermatitis, or rosacea.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving an IGA Score of Clear or Almost Clear and a Score ≥2 Grades Less Than Baseline | Baseline through Week 12 | Percentage of participants in each treatment group achieving an acne severity IGA score of clear (score=0) or almost clear (score=1) and achieving an acne severity IGA score of at least 2 grades less than Baseline. |
| Change From Baseline in Inflammatory Lesion Counts on the Face at Week 12 | Baseline, Week 12 | Inflammatory lesions were characterized by papules, pustules, nodules, and cysts. Least squares means and standard deviations from an analysis of covariance (ANCOVA) with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline. |
| Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 12 | Baseline, Week 12 | Non-inflammatory lesions were characterized by open comedones (blackheads) and closed comedones (whiteheads). Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving at Least a 4-Point Reduction on Item 5 (Embarrassment) of the Pre-Face | Baseline and Week 12 | Percent of participants in each treatment group achieving at least a 4 point reduction on Item 5 (Embarrassment) of the patient reported evaluation of facial acne compared to Baseline. The Pre-Face is a 7-item questionnaire that assesses acne vulgaris-related signs, symptoms, and impacts. Item 5 of the questionnaire was to assess how embarrassed the participant felt because of the acne at their worst, in the 24 hours prior to administration on an 11-point NRS ranging from 0 (not embarrassed at all) to 10 (extremely embarrassed). |
| Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 8 | Baseline, Week 8 | Non-inflammatory lesions were characterized by open comedones (blackheads) and closed comedones (whiteheads). Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline. |
| Percent Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 12 | Baseline, Week 12 | Non-inflammatory lesions were characterized by open comedones (blackheads) and closed comedones (whiteheads). Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline. |
| Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 4 | Baseline, Week 4 | Non-inflammatory lesions were characterized by open comedones (blackheads) and closed comedones (whiteheads). Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline. |
| Change From Baseline in Inflammatory Lesion Counts on the Face at Week 4 | Baseline, Week 4 | Inflammatory lesions were characterized by papules, pustules, nodules, and cysts. Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline. |
| Change From Baseline in Inflammatory Lesion Counts on the Face at Week 8 | Baseline, Week 8 | Inflammatory lesions were characterized by papules, pustules, nodules, and cysts. Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline. |
| Percent Change From Baseline in Inflammatory Lesion Counts on the Face at Week 12 | Baseline, Week 12 | Inflammatory lesions were characterized by papules, pustules, nodules, and cysts. Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline. |
| Percentage of Participants Achieving at Least a 4-Point Reduction on Item 1 (Pimple) of the Patient-Reported Evaluation of Facial Acne (Pre-Face) | Baseline and Week 12 | Percent of participants in each treatment group achieving at least a 4 point reduction on Item 1 (Pimple) of the patient- reported evaluation of facial acne compared to Baseline. The Pre-Face is a 7-item questionnaire that assesses acne vulgaris-related signs, symptoms, and impacts. Item 1 of the questionnaire was to assess the pimples on the participant's face at their worst in the 24 hours prior to administration on an 11-point numeric rating scale (NRS) ranging from 0 (no pimples at all) to 10 (pimples as bad as you can imagine). |
Countries
United States
Participant flow
Pre-assignment details
Participants were randomized to receive either S6G5T-3 (Encapsulated Benzoyl Peroxide \[E-BPO\] and Encapsulated Tretinoin \[E-ATRA\] Cream, 3%/0.1% \[E-BPO/E-ATRA Cream, 3%/0.1%\]) or vehicle in a 2:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| S6G5T-3 Participants topically applied S6G5T-3, once daily to face for 12 weeks. | 290 |
| S6G5T-8 Vehicle Cream Participants topically applied S6G5T-8 vehicle cream, once daily to face for 12 weeks. | 144 |
| Total | 434 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 0 |
| Overall Study | Lost to Follow-up | 15 | 7 |
| Overall Study | Other Than Specified | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Parent/Guardian | 4 | 0 |
| Overall Study | Withdrawal by Subject | 14 | 5 |
Baseline characteristics
| Characteristic | S6G5T-3 | Total | S6G5T-8 Vehicle Cream |
|---|---|---|---|
| Age, Continuous | 20.1 Years STANDARD_DEVIATION 6.96 | 20.1 Years STANDARD_DEVIATION 6.86 | 20.3 Years STANDARD_DEVIATION 6.67 |
| Baseline Acne Lesion Count on the Face Inflammatory Lesions | 28.2 Lesions STANDARD_DEVIATION 8.7 | 28.0 Lesions STANDARD_DEVIATION 8.64 | 27.5 Lesions STANDARD_DEVIATION 8.52 |
| Baseline Acne Lesion Count on the Face Non-Inflammatory Lesions | 44.6 Lesions STANDARD_DEVIATION 18.03 | 44.7 Lesions STANDARD_DEVIATION 18.27 | 44.9 Lesions STANDARD_DEVIATION 18.82 |
| Baseline Investigator's Global Assessment (IGA) 0 - Clean | 0 Participants | 0 Participants | 0 Participants |
| Baseline Investigator's Global Assessment (IGA) 1 - Almost Clear | 0 Participants | 0 Participants | 0 Participants |
| Baseline Investigator's Global Assessment (IGA) 2 - Mild | 0 Participants | 0 Participants | 0 Participants |
| Baseline Investigator's Global Assessment (IGA) 3 - Moderate | 262 Participants | 395 Participants | 133 Participants |
| Baseline Investigator's Global Assessment (IGA) 4 - Severe | 28 Participants | 38 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 85 Participants | 141 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 204 Participants | 291 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 18 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 52 Participants | 70 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 11 Participants | 18 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 212 Participants | 322 Participants | 110 Participants |
| Sex: Female, Male Female | 173 Participants | 250 Participants | 77 Participants |
| Sex: Female, Male Male | 117 Participants | 184 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 281 | 0 / 138 |
| other Total, other adverse events | 68 / 281 | 4 / 138 |
| serious Total, serious adverse events | 1 / 281 | 1 / 138 |
Outcome results
Primary
Change From Baseline in Inflammatory Lesion Counts on the Face at Week 12
Inflammatory lesions were characterized by papules, pustules, nodules, and cysts. Least squares means and standard deviations from an analysis of covariance (ANCOVA) with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline.
Time frame: Baseline, Week 12
Population: The ITT population consisted of all randomized participants who were dispensed study drug. Multiple imputation (MCMC) was used to impute missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| S6G5T-3 | Change From Baseline in Inflammatory Lesion Counts on the Face at Week 12 | -16.2 Inflammatory Lesions | Standard Deviation 9.07 |
| S6G5T-8 Vehicle Cream | Change From Baseline in Inflammatory Lesion Counts on the Face at Week 12 | -14.1 Inflammatory Lesions | Standard Deviation 8.68 |
Primary
Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 12
Non-inflammatory lesions were characterized by open comedones (blackheads) and closed comedones (whiteheads). Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline.
Time frame: Baseline, Week 12
Population: The ITT population consisted of all randomized participants who were dispensed study drug. MCMC was used to impute missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| S6G5T-3 | Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 12 | -24.2 Non-Inflammatory Lesions | Standard Deviation 15.82 |
| S6G5T-8 Vehicle Cream | Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 12 | -17.4 Non-Inflammatory Lesions | Standard Deviation 15.82 |
Primary
Percentage of Participants Achieving an IGA Score of Clear or Almost Clear and a Score ≥2 Grades Less Than Baseline
Percentage of participants in each treatment group achieving an acne severity IGA score of clear (score=0) or almost clear (score=1) and achieving an acne severity IGA score of at least 2 grades less than Baseline.
Time frame: Baseline through Week 12
Population: The ITT population consisted of all randomized participants who were dispensed study drug. MCMC was used to impute missing values. Here, 'Overall Number of Participants Analyzed' (N) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S6G5T-3 | Percentage of Participants Achieving an IGA Score of Clear or Almost Clear and a Score ≥2 Grades Less Than Baseline | 25.4 percentage of participants |
| S6G5T-8 Vehicle Cream | Percentage of Participants Achieving an IGA Score of Clear or Almost Clear and a Score ≥2 Grades Less Than Baseline | 14.7 percentage of participants |
Secondary
Change From Baseline in Inflammatory Lesion Counts on the Face at Week 4
Inflammatory lesions were characterized by papules, pustules, nodules, and cysts. Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline.
Time frame: Baseline, Week 4
Population: The ITT population consisted of all randomized participants who were dispensed study drug. MCMC was used to impute missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| S6G5T-3 | Change From Baseline in Inflammatory Lesion Counts on the Face at Week 4 | -10.7 Inflammatory Lesions | Standard Deviation 7.94 |
| S6G5T-8 Vehicle Cream | Change From Baseline in Inflammatory Lesion Counts on the Face at Week 4 | -10.1 Inflammatory Lesions | Standard Deviation 7.81 |
Secondary
Change From Baseline in Inflammatory Lesion Counts on the Face at Week 8
Inflammatory lesions were characterized by papules, pustules, nodules, and cysts. Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline.
Time frame: Baseline, Week 8
Population: The ITT population consisted of all randomized participants who were dispensed study drug. MCMC was used to impute missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| S6G5T-3 | Change From Baseline in Inflammatory Lesion Counts on the Face at Week 8 | -14.0 Inflammatory Lesions | Standard Deviation 8.57 |
| S6G5T-8 Vehicle Cream | Change From Baseline in Inflammatory Lesion Counts on the Face at Week 8 | -12.5 Inflammatory Lesions | Standard Deviation 8.57 |
Secondary
Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 4
Non-inflammatory lesions were characterized by open comedones (blackheads) and closed comedones (whiteheads). Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline.
Time frame: Baseline, Week 4
Population: The ITT population consisted of all randomized participants who were dispensed study drug. MCMC was used to impute missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| S6G5T-3 | Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 4 | -14.6 Non-Inflammatory Lesions | Standard Deviation 14.51 |
| S6G5T-8 Vehicle Cream | Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 4 | -10.8 Non-Inflammatory Lesions | Standard Deviation 14.88 |
Secondary
Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 8
Non-inflammatory lesions were characterized by open comedones (blackheads) and closed comedones (whiteheads). Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline.
Time frame: Baseline, Week 8
Population: The ITT population consisted of all randomized participants who were dispensed study drug. MCMC was used to impute missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| S6G5T-3 | Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 8 | -20.0 Non-Inflammatory Lesions | Standard Deviation 16.43 |
| S6G5T-8 Vehicle Cream | Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 8 | -12.8 Non-Inflammatory Lesions | Standard Deviation 16.21 |
Secondary
Percentage of Participants Achieving at Least a 4-Point Reduction on Item 1 (Pimple) of the Patient-Reported Evaluation of Facial Acne (Pre-Face)
Percent of participants in each treatment group achieving at least a 4 point reduction on Item 1 (Pimple) of the patient- reported evaluation of facial acne compared to Baseline. The Pre-Face is a 7-item questionnaire that assesses acne vulgaris-related signs, symptoms, and impacts. Item 1 of the questionnaire was to assess the pimples on the participant's face at their worst in the 24 hours prior to administration on an 11-point numeric rating scale (NRS) ranging from 0 (no pimples at all) to 10 (pimples as bad as you can imagine).
Time frame: Baseline and Week 12
Population: The ITT population consisted of all randomized participants who were dispensed study drug. MCMC was used to impute missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S6G5T-3 | Percentage of Participants Achieving at Least a 4-Point Reduction on Item 1 (Pimple) of the Patient-Reported Evaluation of Facial Acne (Pre-Face) | 35.1 Percentage of Participants |
| S6G5T-8 Vehicle Cream | Percentage of Participants Achieving at Least a 4-Point Reduction on Item 1 (Pimple) of the Patient-Reported Evaluation of Facial Acne (Pre-Face) | 27.2 Percentage of Participants |
Secondary
Percentage of Participants Achieving at Least a 4-Point Reduction on Item 5 (Embarrassment) of the Pre-Face
Percent of participants in each treatment group achieving at least a 4 point reduction on Item 5 (Embarrassment) of the patient reported evaluation of facial acne compared to Baseline. The Pre-Face is a 7-item questionnaire that assesses acne vulgaris-related signs, symptoms, and impacts. Item 5 of the questionnaire was to assess how embarrassed the participant felt because of the acne at their worst, in the 24 hours prior to administration on an 11-point NRS ranging from 0 (not embarrassed at all) to 10 (extremely embarrassed).
Time frame: Baseline and Week 12
Population: The ITT population consisted of all randomized participants who were dispensed study drug. MCMC was used to impute missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S6G5T-3 | Percentage of Participants Achieving at Least a 4-Point Reduction on Item 5 (Embarrassment) of the Pre-Face | 33.9 Percentage of Participants |
| S6G5T-8 Vehicle Cream | Percentage of Participants Achieving at Least a 4-Point Reduction on Item 5 (Embarrassment) of the Pre-Face | 37.1 Percentage of Participants |
Secondary
Percent Change From Baseline in Inflammatory Lesion Counts on the Face at Week 12
Inflammatory lesions were characterized by papules, pustules, nodules, and cysts. Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline.
Time frame: Baseline, Week 12
Population: The ITT population consisted of all randomized participants who were dispensed study drug. MCMC was used to impute missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| S6G5T-3 | Percent Change From Baseline in Inflammatory Lesion Counts on the Face at Week 12 | -57.6 Percent Change | Standard Deviation 32.41 |
| S6G5T-8 Vehicle Cream | Percent Change From Baseline in Inflammatory Lesion Counts on the Face at Week 12 | -50.8 Percent Change | Standard Deviation 31.17 |
Secondary
Percent Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 12
Non-inflammatory lesions were characterized by open comedones (blackheads) and closed comedones (whiteheads). Least squares means and standard deviations from an ANCOVA with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline.
Time frame: Baseline, Week 12
Population: The ITT population consisted of all randomized participants who were dispensed study drug. MCMC was used to impute missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| S6G5T-3 | Percent Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 12 | -54.4 Percent Change | Standard Deviation 32.28 |
| S6G5T-8 Vehicle Cream | Percent Change From Baseline in Non-Inflammatory Lesion Counts on the Face at Week 12 | -41.5 Percent Change | Standard Deviation 33.44 |