Facial Papulopustular Rosacea
Conditions
Keywords
Topical Minocycline Foam, 2-Arm study, Inflammatory lesion counts, Investigator's Global Assessment score
Brief summary
The primary objectives of this study are to determine the efficacy and safety of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea.
Detailed description
This is a randomized, multicenter, double-blind, vehicle-controlled, 2 arm study to evaluate the safety and efficacy of FMX103 topical foam containing 1.5% minocycline compared to vehicle, in the treatment of participants with moderate-to-severe facial papulopustular rosacea. Qualified participants will be randomized in a 2:1 ratio (active:vehicle) to receive 1 of the following 2 treatments: * FMX103 minocycline foam 1.5% * Vehicle foam Participants will be assigned to 1 of 2 treatments according to the randomization schedule. Participants will apply (or have applied) the study drug topically once daily for 12 weeks as directed. Participants will be advised to use the study drug at approximately the same time each day. Both the Investigator and participant will be blinded to the study drug identity. Participants will return for visits at Weeks 1, 4, 6, 8, 10, and 12. Efficacy evaluations (inflammatory lesion counts and Investigator's Global Assessment \[IGA\] score) will be performed at Weeks 4, 8, and 12 during the study. Note: Originally the two studies FX2016-11 and FX2016-12 were combinedly presented in the protocol registration form under one NCT number (NCT03142451), and later separated since results were analyzed separately.
Interventions
Dosage form description: Foam containing minocycline HCl 1.5%. Once daily application of a sufficient amount of foam to cover the entire face. Estimated maximum is 0.5 g of drug product containing 7.5 mg (1.5% active) of minocycline. Participants will apply a small amount of the drug as a thin layer over all areas of the face. Participants should apply the drug at approximately the same time each day, about 1 hour before bedtime.
DRUGVehicle foam
Dosage form description: Foam containing minocycline vehicle foam. Once daily application of a sufficient amount of foam to cover the entire face. Estimated maximum is 0.5 g of drug product containing 0.0 mg (vehicle) of minocycline. Participants will apply a small amount of the drug as a thin layer over all areas of the face. Participants should apply the drug at approximately the same time each day, about 1 hour before bedtime.
Sponsors
Premier Research
Vyne Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a double-blind study, with limited access to the randomization code. The randomization code will be held in confidence until after the study database is locked and a memo documenting the database lock has been issued. Every effort will be made to retain the integrity of the blind. When issued to the sites, the study drug will be identical in appearance for all participants, regardless of treatment assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Moderate-to-severe rosacea (as per the IGA score) on the proposed facial treatment area consisting of: 1. At least 15 and not more than 75 facial papules and pustules, excluding lesions involving the eyes and scalp; 2. No more than 2 nodules on the face. 2. Presence of or history of erythema and/or flushing on the face.
Exclusion criteria
1. Presence of any skin condition and/or Excessive facial hair, on the face that would interfere with the diagnosis or assessment of rosacea. 2. Moderate or severe rhinophyma, dense telangiectasia (score 3, severe), or plaque-like facial edema. 3. History of hypersensitivity or allergy to minocycline, any other tetracycline, or of any other component of the formulation. 4. Active ocular rosacea (eg, conjunctivitis, blepharitis, or keratitis) of sufficient severity to require topical or systemic antibiotics.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Count at Week 12 | Baseline and Week 12 | To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. Lesion counts included the number of papules, pustules, and nodules. Change from Baseline was calculated as the value at Baseline minus the post-Baseline value. Thus, a positive change reflects a reduction in lesion count. |
| Percentage of Participants Achieving Investigator Global Assessments (IGA) Treatment Success at Week 12 | Week 12 | To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. The Investigator assessed the global severity of rosacea using the IGA scale. The scale ranges from 0 (Clear): No inflammatory papules or pustules to 4 (Severe): Many inflammatory papules or pustules, and up to 2 nodules. Higher scores indicated severe outcome. Treatment success was defined as an IGA score of 0 (clear) or 1 (almost clear), and at least a 2-step improvement (decrease) from Day 0/Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Counts at Week 4 and Week 8 | Baseline, Week 4 and Week 8 | To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. Lesion counts included the number of papules, pustules, and nodules. Change from Baseline was calculated as the value at Baseline minus the post-Baseline value. Thus, a positive change reflects a reduction in lesion count. |
| Percentage of Participants Achieving IGA Treatment Success of at Least 2 Grades at Week 12 | Week 12 | To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. The Investigator assessed the global severity of rosacea using the IGA scale. The scale ranges from 0 (Clear): No inflammatory papules or pustules to 4 (Severe): Many inflammatory papules or pustules, and up to 2 nodules. Higher scores indicated severe outcome. Treatment success was defined as a 2-grade improvement (decrease) in score at Week 12 compared to Day 0/Baseline. |
| Number of Participants With Adverse Events (AEs) | From Day 0/Baseline until the Safety Follow-up (4 weeks after Week 12 [Final Visit]) | To evaluate the tolerability and safety of topical minocycline foam applied once daily for 12 weeks. A Treatment-emergent adverse events (TEAE) was defined as any AE with an onset date on or after the first application of study drug, and before to the last application of study drug plus 3 days, having been absent pre-treatment or worsening relative to the pre-treatment state. |
| Percentage of Participants Achieving IGA Treatment Success at Week 4 and Week 8 | Week 4 and Week 8 | To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. The Investigator assessed the global severity of rosacea using the IGA scale. The scale ranges from 0 (Clear): No inflammatory papules or pustules to 4 (Severe): Many inflammatory papules or pustules, and up to 2 nodules. Higher scores indicated severe outcome. Treatment success was defined as an IGA score of 0 (clear) or 1 (almost clear), and at least a 2-grade improvement (decrease) from Day 0/Baseline. |
| The Percent Change From Day 0/Baseline in Inflammatory Lesion Count at Week 12 | Baseline and Week 12 | To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. Lesion counts included the number of papules, pustules, and nodules. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 46 sites in the United States from 01 June 2017 - 31 July 2018.
Pre-assignment details
All participants underwent inclusion and exclusion criteria assessment and all eligible participants signed the informed consent before undergoing any study related procedures. All the study assessments were performed as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| FMX103 1.5% Participants applied the assigned FMX103 minocycline foam 1.5% topically once daily for 12 weeks as directed. | 514 |
| Vehicle Foam Participants applied the assigned vehicle foam topically once daily for 12 weeks as directed. | 257 |
| Total | 771 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lost to Follow-up | 15 | 9 |
| Overall Study | Other | 6 | 2 |
| Overall Study | Participant request | 11 | 7 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Vehicle Foam | Total | FMX103 1.5% |
|---|---|---|---|
| Age, Continuous | 50.9 years STANDARD_DEVIATION 13.49 | 50.9 years STANDARD_DEVIATION 13.75 | 50.9 years STANDARD_DEVIATION 13.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 86 Participants | 252 Participants | 166 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 171 Participants | 519 Participants | 348 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 8 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 250 Participants | 749 Participants | 499 Participants |
| Sex: Female, Male Female | 168 Participants | 533 Participants | 365 Participants |
| Sex: Female, Male Male | 89 Participants | 238 Participants | 149 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 514 | 0 / 257 |
| other Total, other adverse events | 39 / 514 | 22 / 257 |
| serious Total, serious adverse events | 1 / 514 | 2 / 257 |
Outcome results
Primary
Percentage of Participants Achieving Investigator Global Assessments (IGA) Treatment Success at Week 12
To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. The Investigator assessed the global severity of rosacea using the IGA scale. The scale ranges from 0 (Clear): No inflammatory papules or pustules to 4 (Severe): Many inflammatory papules or pustules, and up to 2 nodules. Higher scores indicated severe outcome. Treatment success was defined as an IGA score of 0 (clear) or 1 (almost clear), and at least a 2-step improvement (decrease) from Day 0/Baseline.
Time frame: Week 12
Population: The ITT population included all randomized participants. Analyses using the ITT population were based on the randomized treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FMX103 1.5% | Percentage of Participants Achieving Investigator Global Assessments (IGA) Treatment Success at Week 12 | 49.1 Percentage of participants |
| Vehicle Foam | Percentage of Participants Achieving Investigator Global Assessments (IGA) Treatment Success at Week 12 | 39.0 Percentage of participants |
p-value: 0.007795% CI: [1.064, 1.499]Cochran-Mantel-Haenszel
Primary
The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Count at Week 12
To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. Lesion counts included the number of papules, pustules, and nodules. Change from Baseline was calculated as the value at Baseline minus the post-Baseline value. Thus, a positive change reflects a reduction in lesion count.
Time frame: Baseline and Week 12
Population: The intent to treat (ITT) population included all randomized participants. Analyses using the ITT population were based on the randomized treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FMX103 1.5% | The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Count at Week 12 | 18.38 Lesions | Standard Error 0.508 |
| Vehicle Foam | The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Count at Week 12 | 14.53 Lesions | Standard Error 0.715 |
p-value: <0.000195% CI: [2.16, 5.54]ANCOVA
Secondary
Number of Participants With Adverse Events (AEs)
To evaluate the tolerability and safety of topical minocycline foam applied once daily for 12 weeks. A Treatment-emergent adverse events (TEAE) was defined as any AE with an onset date on or after the first application of study drug, and before to the last application of study drug plus 3 days, having been absent pre-treatment or worsening relative to the pre-treatment state.
Time frame: From Day 0/Baseline until the Safety Follow-up (4 weeks after Week 12 [Final Visit])
Population: The Safety (SAF) population included all randomized participants who used at least 1 dose of study drug, including participants who had no post-Baseline assessments unless all dispensed study drug was returned unused. Analyses using the SAF population were based on the treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FMX103 1.5% | Number of Participants With Adverse Events (AEs) | Treatment-related TEAEs | 13 Participants |
| FMX103 1.5% | Number of Participants With Adverse Events (AEs) | Adverse events leading to study discontinuation | 2 Participants |
| FMX103 1.5% | Number of Participants With Adverse Events (AEs) | All adverse events | 134 Participants |
| FMX103 1.5% | Number of Participants With Adverse Events (AEs) | TEAEs | 124 Participants |
| FMX103 1.5% | Number of Participants With Adverse Events (AEs) | Serious TEAEs (Serious AEs [SAEs]) | 1 Participants |
| FMX103 1.5% | Number of Participants With Adverse Events (AEs) | Participants with any severe TEAE | 2 Participants |
| FMX103 1.5% | Number of Participants With Adverse Events (AEs) | TEAEs resulting in death | 0 Participants |
| Vehicle Foam | Number of Participants With Adverse Events (AEs) | Adverse events leading to study discontinuation | 0 Participants |
| Vehicle Foam | Number of Participants With Adverse Events (AEs) | Treatment-related TEAEs | 6 Participants |
| Vehicle Foam | Number of Participants With Adverse Events (AEs) | Serious TEAEs (Serious AEs [SAEs]) | 2 Participants |
| Vehicle Foam | Number of Participants With Adverse Events (AEs) | TEAEs | 67 Participants |
| Vehicle Foam | Number of Participants With Adverse Events (AEs) | TEAEs resulting in death | 0 Participants |
| Vehicle Foam | Number of Participants With Adverse Events (AEs) | All adverse events | 71 Participants |
| Vehicle Foam | Number of Participants With Adverse Events (AEs) | Participants with any severe TEAE | 2 Participants |
Secondary
Percentage of Participants Achieving IGA Treatment Success at Week 4 and Week 8
To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. The Investigator assessed the global severity of rosacea using the IGA scale. The scale ranges from 0 (Clear): No inflammatory papules or pustules to 4 (Severe): Many inflammatory papules or pustules, and up to 2 nodules. Higher scores indicated severe outcome. Treatment success was defined as an IGA score of 0 (clear) or 1 (almost clear), and at least a 2-grade improvement (decrease) from Day 0/Baseline.
Time frame: Week 4 and Week 8
Population: The ITT population included all randomized participants. Analyses using the ITT population were based on the randomized treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FMX103 1.5% | Percentage of Participants Achieving IGA Treatment Success at Week 4 and Week 8 | Week 4 | 16.7 Percentage of participants |
| FMX103 1.5% | Percentage of Participants Achieving IGA Treatment Success at Week 4 and Week 8 | Week 8 | 40.3 Percentage of participants |
| Vehicle Foam | Percentage of Participants Achieving IGA Treatment Success at Week 4 and Week 8 | Week 4 | 9.7 Percentage of participants |
| Vehicle Foam | Percentage of Participants Achieving IGA Treatment Success at Week 4 and Week 8 | Week 8 | 30.7 Percentage of participants |
Comparison: Statistical Analysis For Week 4p-value: 0.011495% CI: [1.129, 2.605]Cochran-Mantel-Haenszel
Comparison: Statistical Analysis For Week 8p-value: 0.006195% CI: [1.082, 1.607]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving IGA Treatment Success of at Least 2 Grades at Week 12
To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. The Investigator assessed the global severity of rosacea using the IGA scale. The scale ranges from 0 (Clear): No inflammatory papules or pustules to 4 (Severe): Many inflammatory papules or pustules, and up to 2 nodules. Higher scores indicated severe outcome. Treatment success was defined as a 2-grade improvement (decrease) in score at Week 12 compared to Day 0/Baseline.
Time frame: Week 12
Population: The ITT population included all randomized participants. Analyses using the ITT population were based on the randomized treatment.~Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FMX103 1.5% | Percentage of Participants Achieving IGA Treatment Success of at Least 2 Grades at Week 12 | 53.8 Percentage of participants |
| Vehicle Foam | Percentage of Participants Achieving IGA Treatment Success of at Least 2 Grades at Week 12 | 45.1 Percentage of participants |
p-value: 0.018995% CI: [1.024, 1.39]Cochran-Mantel-Haenszel
Secondary
The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Counts at Week 4 and Week 8
To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. Lesion counts included the number of papules, pustules, and nodules. Change from Baseline was calculated as the value at Baseline minus the post-Baseline value. Thus, a positive change reflects a reduction in lesion count.
Time frame: Baseline, Week 4 and Week 8
Population: The ITT population included all randomized participants. Analyses using the ITT population were based on the randomized treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FMX103 1.5% | The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Counts at Week 4 and Week 8 | Week 4 | 12.67 Lesions | Standard Error 0.484 |
| FMX103 1.5% | The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Counts at Week 4 and Week 8 | Week 8 | 17.15 Lesions | Standard Error 0.471 |
| Vehicle Foam | The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Counts at Week 4 and Week 8 | Week 4 | 8.29 Lesions | Standard Error 0.678 |
| Vehicle Foam | The Absolute Change From Day 0/Baseline in the Inflammatory Lesion Counts at Week 4 and Week 8 | Week 8 | 12.08 Lesions | Standard Error 0.649 |
Comparison: Statistical Analysis For Week 4p-value: <0.000195% CI: [2.77, 5.99]ANCOVA
Comparison: Statistical Analysis For Week 8p-value: <0.000195% CI: [3.52, 6.63]ANCOVA
Secondary
The Percent Change From Day 0/Baseline in Inflammatory Lesion Count at Week 12
To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea. Lesion counts included the number of papules, pustules, and nodules.
Time frame: Baseline and Week 12
Population: The ITT population included all randomized participants. Analyses using the ITT population were based on the randomized treatment.~Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FMX103 1.5% | The Percent Change From Day 0/Baseline in Inflammatory Lesion Count at Week 12 | 61.45 Percent change | Standard Error 1.578 |
| Vehicle Foam | The Percent Change From Day 0/Baseline in Inflammatory Lesion Count at Week 12 | 50.16 Percent change | Standard Error 2.221 |
p-value: <0.000195% CI: [6.05, 16.54]ANCOVA