Acne Vulgaris
Conditions
Brief summary
This is a 12 week, multi-center, double-blinded, randomized, vehicle-controlled, parallel group, study to be conducted in approximately 1300 subjects with acne vulgaris in the US.
Detailed description
This is a double-blind, placebo controlled study in subjects with moderate to severe acne. Subjects who satisfy the entry criteria will be randomized to SB204 4% QD or Vehicle Gel QD in a 1:1 ratio. Efficacy assessments will include Investigator Global Assessments (IGA) and inflammatory and non-inflammatory lesion counts. Subjects will return for post-Baseline evaluation at Weeks 2, 4, 8, and 12/Early Termination (ET).
Interventions
DRUGSB204 4%
Once daily
DRUGVehicle Gel
Placebo comparator
Sponsors
Chiltern International Inc.
Novan, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
9 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Moderate to severe acne * Minimum of 25 and no more than 70 non-inflammatory lesions (open and closed comedones) on the face * Minimum of 20 and no more than 40 inflammatory lesions (papules and pustules)
Exclusion criteria
* Women of child-bearing potential who are pregnant, nursing, considering becoming pregnant * Any dermatologic condition that could interfere with clinical evaluations including severe, recalcitrant cystic acne
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Inflammatory Lesion Counts | Baseline and Week 12 | The absolute change from Baseline in inflammatory lesion counts was to be assessed on the face only (forehead, right and left cheeks, chin, and nose). Inflammatory lesions included papules, pustules, nodules, and cysts. |
| Absolute Change From Baseline in Non-inflammatory Lesion Counts | Baseline and Week 12 | The absolute change from Baseline in non-inflammatory lesion counts was to be assessed on the face only (forehead, right and left cheeks, chin, and nose). Non-inflammatory lesions included open comedones (blackheads) and closed comedones (whiteheads). |
| Proportion of Subjects With Investigator Global Assessment (IGA) Success at Week 12 | Baseline and Week 12 | Proportion of subjects with Investigator Global Assessment (IGA) Success at Week 12 is defined as an IGA score of 0 or 1 (Clear/Almost Clear) and at least a 2 grade improvement from Baseline. The IGA scale is as follows: Grade Description 0 Clear: Clear skin with no inflammatory or non-inflammatory lesions. 1. Almost clear: Rare non-inflammatory lesions with rare papules (papules may be resolving and hyperpigmented, though not pink-red). 2. Mild: Some non-inflammatory lesions with no more than a few inflammatory lesions. 3. Moderate: Up to many non-inflammatory lesions and may have some inflammatory lesions, but no more than one nodulocystic lesion. 4. Severe: Up to many non-inflammatory and inflammatory lesions, but no more than a few nodulocystic lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Inflammatory Lesion Count | Baseline and Week 12 | The percent change from baseline in inflammatory lesion count |
| Percent Change in Non-inflammatory Lesion Count | Baseline and Week 12 | The percent change from baseline in non-inflammatory lesion count |
| Time to Reduction in Inflammatory Lesion Counts | Week 12 | Median time to a 35% reduction in inflammatory lesion count (Kaplan-Meier) |
| Time to Improvement in IGA | Week 12 | Median time to a 2 or more grade improvement in IGA (Kaplan-Meier analysis). |
Countries
United States
Participant flow
Recruitment details
1300 participants were planned to be recruited from dermatologists and other (e. g. family physicians, research clinics). A total of 1307 participants were randomized. Enrollment began on 22Feb2016 and the last subject completed on 21Dec2016. There were 1306 participants in the intent to treat (ITT) and safety populations.
Participants by arm
| Arm | Count |
|---|---|
| SB204 4% SB204 4% topically once daily | 652 |
| Vehicle Gel Vehicle Gel (placebo comparator) topically once daily | 654 |
| Total | 1,306 |
Baseline characteristics
| Characteristic | SB204 4% | Total | Vehicle Gel |
|---|---|---|---|
| Age, Continuous | 21.1 years STANDARD_DEVIATION 8.25 | 21.2 years STANDARD_DEVIATION 8.32 | 21.3 years STANDARD_DEVIATION 8.38 |
| Baseline Investigator Global Assessment 0--clear | 0 Participants | 0 Participants | 0 Participants |
| Baseline Investigator Global Assessment 1--almost clear | 0 Participants | 0 Participants | 0 Participants |
| Baseline Investigator Global Assessment 2--mild | 0 Participants | 0 Participants | 0 Participants |
| Baseline Investigator Global Assessment 3--moderate | 557 Participants | 1132 Participants | 575 Participants |
| Baseline Investigator Global Assessment 4--severe | 94 Participants | 172 Participants | 78 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 28 Participants | 54 Participants | 26 Participants |
| Race (NIH/OMB) Black or African American | 143 Participants | 291 Participants | 148 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 20 Participants | 41 Participants | 21 Participants |
| Race (NIH/OMB) White | 456 Participants | 911 Participants | 455 Participants |
| Region of Enrollment United States | 652 Participants | 1306 Participants | 654 Participants |
| Sex: Female, Male Female | 400 Participants | 806 Participants | 406 Participants |
| Sex: Female, Male Male | 252 Participants | 500 Participants | 248 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 654 | 1 / 652 |
| other Total, other adverse events | 66 / 654 | 10 / 652 |
| serious Total, serious adverse events | 0 / 654 | 4 / 652 |
Outcome results
Primary
Absolute Change From Baseline in Inflammatory Lesion Counts
The absolute change from Baseline in inflammatory lesion counts was to be assessed on the face only (forehead, right and left cheeks, chin, and nose). Inflammatory lesions included papules, pustules, nodules, and cysts.
Time frame: Baseline and Week 12
Population: Intent To Treat population (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB204 4% | Absolute Change From Baseline in Inflammatory Lesion Counts | -12.4 inflammatory acne lesions | Standard Deviation 10.3 |
| Vehicle Gel | Absolute Change From Baseline in Inflammatory Lesion Counts | -11.3 inflammatory acne lesions | Standard Deviation 10.46 |
Primary
Absolute Change From Baseline in Non-inflammatory Lesion Counts
The absolute change from Baseline in non-inflammatory lesion counts was to be assessed on the face only (forehead, right and left cheeks, chin, and nose). Non-inflammatory lesions included open comedones (blackheads) and closed comedones (whiteheads).
Time frame: Baseline and Week 12
Population: Intent to Treat population (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB204 4% | Absolute Change From Baseline in Non-inflammatory Lesion Counts | -16.0 non-inflammatory acne lesions | Standard Deviation 16.36 |
| Vehicle Gel | Absolute Change From Baseline in Non-inflammatory Lesion Counts | -13.5 non-inflammatory acne lesions | Standard Deviation 16.97 |
Primary
Proportion of Subjects With Investigator Global Assessment (IGA) Success at Week 12
Proportion of subjects with Investigator Global Assessment (IGA) Success at Week 12 is defined as an IGA score of 0 or 1 (Clear/Almost Clear) and at least a 2 grade improvement from Baseline. The IGA scale is as follows: Grade Description 0 Clear: Clear skin with no inflammatory or non-inflammatory lesions. 1. Almost clear: Rare non-inflammatory lesions with rare papules (papules may be resolving and hyperpigmented, though not pink-red). 2. Mild: Some non-inflammatory lesions with no more than a few inflammatory lesions. 3. Moderate: Up to many non-inflammatory lesions and may have some inflammatory lesions, but no more than one nodulocystic lesion. 4. Severe: Up to many non-inflammatory and inflammatory lesions, but no more than a few nodulocystic lesions
Time frame: Baseline and Week 12
Population: ITT population; subjects who had a Week 12 (study completion) visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SB204 4% | Proportion of Subjects With Investigator Global Assessment (IGA) Success at Week 12 | 83 Participants |
| Vehicle Gel | Proportion of Subjects With Investigator Global Assessment (IGA) Success at Week 12 | 84 Participants |
Secondary
Percent Change in Inflammatory Lesion Count
The percent change from baseline in inflammatory lesion count
Time frame: Baseline and Week 12
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB204 4% | Percent Change in Inflammatory Lesion Count | -45.9 Percentage change from baseline | Standard Deviation 36.65 |
| Vehicle Gel | Percent Change in Inflammatory Lesion Count | -43.1 Percentage change from baseline | Standard Deviation 38.68 |
Secondary
Percent Change in Non-inflammatory Lesion Count
The percent change from baseline in non-inflammatory lesion count
Time frame: Baseline and Week 12
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB204 4% | Percent Change in Non-inflammatory Lesion Count | -39.6 Percentage change from baseline | Standard Deviation 35.84 |
| Vehicle Gel | Percent Change in Non-inflammatory Lesion Count | -34.6 Percentage change from baseline | Standard Deviation 41.82 |
Secondary
Time to Improvement in IGA
Median time to a 2 or more grade improvement in IGA (Kaplan-Meier analysis).
Time frame: Week 12
Population: ITT population. Overall number of participants analyzed = number of participants who achieved a 2 or more grade improvement in their IGA score. This was a Kaplan-Meier analysis; for both the SB204 4% and Vehicle Gel treatment groups, the median was not estimable due to \< 50% of subjects achieving a 2 or more grade improvement in their IGA score.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SB204 4% | Time to Improvement in IGA | 25% Quartile | 87.0 Days |
| SB204 4% | Time to Improvement in IGA | 50% Quartile | NA Days |
| SB204 4% | Time to Improvement in IGA | 75% Quartile | NA Days |
| Vehicle Gel | Time to Improvement in IGA | 25% Quartile | 87.0 Days |
| Vehicle Gel | Time to Improvement in IGA | 50% Quartile | NA Days |
| Vehicle Gel | Time to Improvement in IGA | 75% Quartile | NA Days |
Secondary
Time to Reduction in Inflammatory Lesion Counts
Median time to a 35% reduction in inflammatory lesion count (Kaplan-Meier)
Time frame: Week 12
Population: ITT population; overall number of participants analyzed = the # of participants who achieved at least a 35% reduction in their inflammatory lesion counts.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SB204 4% | Time to Reduction in Inflammatory Lesion Counts | 31.0 Days |
| Vehicle Gel | Time to Reduction in Inflammatory Lesion Counts | 31.0 Days |