Acne Vulgaris
Conditions
Keywords
acne
Brief summary
This is a Phase 3 study to evaluate the efficacy, safety and long-term safety of the topical administration of FMX-101, 4% minocycline foam for the treatment of moderate-to-severe acne vulgaris.
Detailed description
This is a Phase 3 study to evaluate the efficacy, safety and long-term safety of the topical administration of FMX-101, 4% minocycline foam for the treatment of moderate-to-severe acne vulgaris. The first 12 weeks of the study involves randomized, double-blind treatment with active FMX-101, 4% or matching vehicle. Subjects who successfully complete the 12-week double blind portion of the study will be offered the opportunity to continue in the trial for up to an additional 40 weeks (for a total of 1 year) and receive open-label treatment with FMX-101, 4%.
Interventions
FMX-101, 4% minocycline foam applied topically once daily for 12 weeks
DRUGVehicle Foam
Vehicle foam applied topically once daily for 12 weeks
Sponsors
Vyne Therapeutics Inc.
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
* Has facial acne vulgaris with: * 20 to 50 inflammatory lesions (papules, pustules, and nodules) * 25 to 100 noninflammatory lesions (open and closed comedones) * No more than 2 nodules on the face * IGA score of moderate (3) to severe (4) * Willing to use only the supplied non-medicated cleanser (Cetaphil Gentle Skin Cleanser) and to refrain from use of any other acne medication, medicated cleanser, excessive sun exposure, and tanning booths for the duration of the study
Exclusion criteria
* Acne conglobata, acne fulminans, secondary acne (chloracne, drug induced acne) or any dermatological condition of the face or facial hair (eg, beard, sideburns, mustache) that could interfere with the clinical evaluations * Sunburn on the face
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in the Inflammatory Lesion Count at Week 12 | Baseline and Week 12 | To evaluate the efficacy in the treatment of acne compared to vehicle of topical FMX101 4% administered daily for 12 weeks. Changes from Baseline are calculated as Baseline value minus post-Baseline value, so that decreases appear as positive values. Inflammatory lesion count included: papules, pustules, and nodules. |
| Percentage of Participants Achieving Investigator's Global Assessments (IGA) Treatment Success at Week 12 | Baseline and Week 12 | The IGA scale for acne vulgaris, was used by the investigators to assess the severity of a participant's acne vulgaris. The scale ranges from 0 (Clear): normal, clear skin with no evidence of acne vulgaris to 5 (Very Severe): highly inflammatory lesions predominate, variable number of comedones, many papules/pustules and many nodulocystic lesions. Higher scores indicated severe outcome. Treatment success was defined as an IGA score of 0 (score of clear) or 1 (almost clear), and at least a 2-grade improvement (decrease) from Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in the Non-inflammatory Lesion Count at Week 12 | Baseline and Week 12 | To evaluate the efficacy in the treatment of acne compared to vehicle of topical FMX101 4% administered daily for 12 weeks. Percent change from baseline is calculated as the baseline value minus the post-baseline value divided by the baseline value, expressed as a percentage. Non-inflammatory lesions included: open comedones (blackhead) and closed comedones (whitehead). |
| Absolute Change From Baseline in the Inflammatory Lesion Count at Week 6 and Week 9 | Baseline, Week 6 and Week 9 | To evaluate the efficacy in the treatment of acne compared to vehicle of topical FMX101 4% administered daily for 12 weeks. Changes from Baseline are calculated as Baseline value minus post-Baseline value, so that decreases appear as positive values. Inflammatory lesion count included: papules, pustules, and nodules. |
| Percentage of Participants Achieving IGA Treatment Success at Week 6 and Week 9 | Baseline, Week 6 and Week 9 | The IGA scale for acne vulgaris, was used by the investigators to assess the severity of a participant's acne vulgaris. The scale ranges from 0 (Clear): normal, clear skin with no evidence of acne vulgaris to 5 (Very Severe): highly inflammatory lesions predominate, variable number of comedones, many papules/pustules and many nodulocystic lesions. Higher scores indicated severe outcome. Treatment success was defined as an IGA score of 0 (score of clear) or 1 (almost clear), and at least a 2-grade improvement (decrease) from Baseline. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Double blind: From Baseline until Week 12; Open-label: Week 16 until Week 52 | To evaluate the safety compared to vehicle of topical FMX101 4% administered daily for 12 weeks and to evaluate the long-term safety of topical FMX101 4% administered daily for up to an additional 40 weeks. TEAEs of the double-blind phase were defined as AEs starting on or after date of first application of investigational product (IP), but before the date of the first application of the open-label phase, and AEs starting on or after the first application of the open-label phase are considered as TEAEs of the open-label phase. |
Countries
Dominican Republic, United States
Participant flow
Recruitment details
The study was conducted at 36 sites in the United States and one site in the Dominican Republic from 11 May 2016 to 13 October 2017.
Pre-assignment details
The study consisted of a varied screening period. All participants underwent inclusion and exclusion criteria assessment and all eligible participants signed the informed consent before undergoing any study related procedures. All assessments at screening were done as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| FMX-101, 4% Minocycline Foam Randomized participants applied FMX101 4% topically to the face once daily for 12 weeks as directed. | 333 |
| Vehicle Foam Randomized participants applied matching vehicle foam topically to the face once daily for 12 weeks as directed. | 162 |
| Total | 495 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Phase | Adverse Event | 1 | 1 |
| Double-Blind Phase | Lost to Follow-up | 10 | 9 |
| Double-Blind Phase | Protocol Violation | 2 | 2 |
| Double-Blind Phase | Subject: withdrew consent; non-compliant with visits; moved;lack of efficacy;positive pregnancy test | 3 | 2 |
| Double-Blind Phase | Withdrawal by Subject | 20 | 11 |
| Open-Label Phase | Administrative | 26 | 12 |
| Open-Label Phase | Adverse Event | 2 | 3 |
| Open-Label Phase | Lost to Follow-up | 18 | 9 |
| Open-Label Phase | Positive pregnancy test; subject- noncompliance; withdrew consent; lack of efficacy etc. | 5 | 2 |
| Open-Label Phase | Protocol Violation | 3 | 0 |
| Open-Label Phase | Withdrawal by Subject | 33 | 18 |
Baseline characteristics
| Characteristic | Vehicle Foam | Total | FMX-101, 4% Minocycline Foam |
|---|---|---|---|
| Age, Continuous | 20.8 Years STANDARD_DEVIATION 7.9 | 20.6 Years STANDARD_DEVIATION 7.9 | 20.5 Years STANDARD_DEVIATION 7.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 65 Participants | 192 Participants | 127 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 97 Participants | 303 Participants | 206 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 | 7 Participants | 17 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants | 103 Participants | 73 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 7 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 124 Participants | 367 Participants | 243 Participants |
| Sex: Female, Male Female | 93 Participants | 290 Participants | 197 Participants |
| Sex: Female, Male Male | 69 Participants | 205 Participants | 136 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 333 | 0 / 162 | 0 / 373 |
| other Total, other adverse events | 40 / 333 | 15 / 162 | 38 / 373 |
| serious Total, serious adverse events | 4 / 333 | 2 / 162 | 1 / 373 |
Outcome results
Primary
Absolute Change From Baseline in the Inflammatory Lesion Count at Week 12
To evaluate the efficacy in the treatment of acne compared to vehicle of topical FMX101 4% administered daily for 12 weeks. Changes from Baseline are calculated as Baseline value minus post-Baseline value, so that decreases appear as positive values. Inflammatory lesion count included: papules, pustules, and nodules.
Time frame: Baseline and Week 12
Population: An ITT population: included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FMX-101, 4% Minocycline Foam | Absolute Change From Baseline in the Inflammatory Lesion Count at Week 12 | 13.78 Lesions | Standard Error 0.66 |
| Vehicle Foam | Absolute Change From Baseline in the Inflammatory Lesion Count at Week 12 | 10.64 Lesions | Standard Error 0.94 |
Comparison: Change from baseline in inflammatory lesion count was analyzed using an analysis of covariance (ANCOVA) model, which included treatment, baseline inflammatory lesion count and pooled investigational site as a blocking factor.p-value: 0.005195% CI: [0.95, 5.35]ANCOVA
Primary
Percentage of Participants Achieving Investigator's Global Assessments (IGA) Treatment Success at Week 12
The IGA scale for acne vulgaris, was used by the investigators to assess the severity of a participant's acne vulgaris. The scale ranges from 0 (Clear): normal, clear skin with no evidence of acne vulgaris to 5 (Very Severe): highly inflammatory lesions predominate, variable number of comedones, many papules/pustules and many nodulocystic lesions. Higher scores indicated severe outcome. Treatment success was defined as an IGA score of 0 (score of clear) or 1 (almost clear), and at least a 2-grade improvement (decrease) from Baseline.
Time frame: Baseline and Week 12
Population: An ITT population: included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FMX-101, 4% Minocycline Foam | Percentage of Participants Achieving Investigator's Global Assessments (IGA) Treatment Success at Week 12 | 14.66 Percentage of participants |
| Vehicle Foam | Percentage of Participants Achieving Investigator's Global Assessments (IGA) Treatment Success at Week 12 | 7.89 Percentage of participants |
p-value: 0.042495% CI: [1.02, 3.46]Mantel Haenszel
Secondary
Absolute Change From Baseline in the Inflammatory Lesion Count at Week 6 and Week 9
To evaluate the efficacy in the treatment of acne compared to vehicle of topical FMX101 4% administered daily for 12 weeks. Changes from Baseline are calculated as Baseline value minus post-Baseline value, so that decreases appear as positive values. Inflammatory lesion count included: papules, pustules, and nodules.
Time frame: Baseline, Week 6 and Week 9
Population: An ITT population: included all randomized population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FMX-101, 4% Minocycline Foam | Absolute Change From Baseline in the Inflammatory Lesion Count at Week 6 and Week 9 | Week 6 | 12.90 Lesions | Standard Error 0.61 |
| FMX-101, 4% Minocycline Foam | Absolute Change From Baseline in the Inflammatory Lesion Count at Week 6 and Week 9 | Week 9 | 13.42 Lesions | Standard Error 0.66 |
| Vehicle Foam | Absolute Change From Baseline in the Inflammatory Lesion Count at Week 6 and Week 9 | Week 9 | 9.64 Lesions | Standard Error 0.94 |
| Vehicle Foam | Absolute Change From Baseline in the Inflammatory Lesion Count at Week 6 and Week 9 | Week 6 | 9.01 Lesions | Standard Error 0.87 |
p-value: 0.000195% CI: [1.88, 5.9]ANCOVA
p-value: 0.000795% CI: [1.6, 5.95]ANCOVA
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
To evaluate the safety compared to vehicle of topical FMX101 4% administered daily for 12 weeks and to evaluate the long-term safety of topical FMX101 4% administered daily for up to an additional 40 weeks. TEAEs of the double-blind phase were defined as AEs starting on or after date of first application of investigational product (IP), but before the date of the first application of the open-label phase, and AEs starting on or after the first application of the open-label phase are considered as TEAEs of the open-label phase.
Time frame: Double blind: From Baseline until Week 12; Open-label: Week 16 until Week 52
Population: Safety population: included all randomized participants who received IP. Participants who had no post-Baseline assessments were included in the Safety population unless all dispensed IP was returned unused.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FMX-101, 4% Minocycline Foam | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 110 Participants |
| FMX-101, 4% Minocycline Foam | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any Treatment-related TEAE | 9 Participants |
| FMX-101, 4% Minocycline Foam | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any Serious TEAE | 4 Participants |
| FMX-101, 4% Minocycline Foam | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE Leading to IP discontinuation | 1 Participants |
| Vehicle Foam | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE Leading to IP discontinuation | 1 Participants |
| Vehicle Foam | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 45 Participants |
| Vehicle Foam | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any Serious TEAE | 2 Participants |
| Vehicle Foam | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any Treatment-related TEAE | 3 Participants |
| Open-label-FMX-101, 4% Minocycline Foam | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE Leading to IP discontinuation | 5 Participants |
| Open-label-FMX-101, 4% Minocycline Foam | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any Treatment-related TEAE | 8 Participants |
| Open-label-FMX-101, 4% Minocycline Foam | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any Serious TEAE | 1 Participants |
| Open-label-FMX-101, 4% Minocycline Foam | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 120 Participants |
Secondary
Percentage of Participants Achieving IGA Treatment Success at Week 6 and Week 9
The IGA scale for acne vulgaris, was used by the investigators to assess the severity of a participant's acne vulgaris. The scale ranges from 0 (Clear): normal, clear skin with no evidence of acne vulgaris to 5 (Very Severe): highly inflammatory lesions predominate, variable number of comedones, many papules/pustules and many nodulocystic lesions. Higher scores indicated severe outcome. Treatment success was defined as an IGA score of 0 (score of clear) or 1 (almost clear), and at least a 2-grade improvement (decrease) from Baseline.
Time frame: Baseline, Week 6 and Week 9
Population: An ITT population: included all randomized population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FMX-101, 4% Minocycline Foam | Percentage of Participants Achieving IGA Treatment Success at Week 6 and Week 9 | Week 6 | 4.68 Percentage of participants |
| FMX-101, 4% Minocycline Foam | Percentage of Participants Achieving IGA Treatment Success at Week 6 and Week 9 | Week 9 | 7.61 Percentage of participants |
| Vehicle Foam | Percentage of Participants Achieving IGA Treatment Success at Week 6 and Week 9 | Week 6 | 0.81 Percentage of participants |
| Vehicle Foam | Percentage of Participants Achieving IGA Treatment Success at Week 6 and Week 9 | Week 9 | 5.97 Percentage of participants |
p-value: 0.007195% CI: [1.06, 6.69]Cochran-Mantel-Haenszel
p-value: 0.514395% CI: [-3.3, 6.58]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in the Non-inflammatory Lesion Count at Week 12
To evaluate the efficacy in the treatment of acne compared to vehicle of topical FMX101 4% administered daily for 12 weeks. Percent change from baseline is calculated as the baseline value minus the post-baseline value divided by the baseline value, expressed as a percentage. Non-inflammatory lesions included: open comedones (blackhead) and closed comedones (whitehead).
Time frame: Baseline and Week 12
Population: An ITT Population: included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FMX-101, 4% Minocycline Foam | Percent Change From Baseline in the Non-inflammatory Lesion Count at Week 12 | 26.33 Percent Change | Standard Error 2.88 |
| Vehicle Foam | Percent Change From Baseline in the Non-inflammatory Lesion Count at Week 12 | 13.49 Percent Change | Standard Error 4.66 |
p-value: 0.015595% CI: [2.44, 23.23]ANCOVA