Acne Vulgaris
Conditions
Keywords
Acne vulgaris, Trifarotene, AKLIEF®, CD5789
Brief summary
The purpose of this study is to evaluate the safety and efficacy of trifarotene 50 microgram per gram (mcg/g) cream compared to its vehicle on the risk of formation of atrophic acne scars after 24 weeks of treatment in facial acne participants assessed by atrophic acne scars count.
Interventions
Participants will apply a thin a layer of trifarotene (CD5789) 50 mcg/g cream to the face once daily, in the evening for 24 weeks
Participants will apply a thin a layer of trifarotene vehicle cream to the face once daily, in the evening for 24 weeks
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
17 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participant with clinical diagnosis of acne vulgaris on the face as defined by (excluding the nose and middle zone of approximately 2 centimeter \[cm\]): 1. Investigator's Global Assessment (IGA) score of 3 (Moderate) or 4 (Severe), with the same score on both sides of the face; and 2. A minimum of 20 inflammatory lesions (papules and pustules) in total with at least 10 on each side; and 3. No more than 2 nodules (greater than or equal to \[\>=\] 1 cm in diameter) on the face; and 4. A minimum of 10 atrophic acne scars in total (\>2 mm) * Participant with a symmetrical number of the following lesions/scars on the whole face: 1. Inflammatory and non-inflammatory lesions; and 2. Atrophic acne scars (minimum of 4 scars per half-face) * The participant is a female of non-childbearing potential * If a female of childbearing, potential uses oral contraceptives that are also approve for treating acne vulgaris * Other protocol defined inclusion criteria could apply Key
Exclusion criteria
* Participant with acne conglobata, acne fulminans, secondary acne, nodulocystic acne and acne requiring systemic treatment * Participant with any acne cyst on the face or with more than 3 excoriated acne lesions * Participant with known active or chronic allergies or suspected allergy to trifarotene or excipients of the formulation * Participant with facial dermal conditions (for example, tattoo, skin abrasion, eczema, sunburned skin, scars, nevi, etc.) that may interfere with study assessments in the opinion of the investigator * Participant with known impaired hepatic or renal functions, based on medical history
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half Face at Week 24 | Baseline, Week 24 | The scars were counted according to their size defined in two categories using 2 millimeter (mm) and 4 mm punch biopsy tools for size classification: 1) atrophic scars 2 to 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types; 2) atrophic scars greater than (\>) 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types. Each type of atrophic acne scar was counted separately for each half-face by the evaluator for following regions: right forehead, right cheek, right side of the chin, left forehead, left cheek and left side of the chin. To obtain the total number of atrophic scars per half-face, atrophic acne scar counts for each half-face was added. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Baseline, up to Week 20 | The scars were counted according to their size defined in two categories using 2 mm and 4 mm punch biopsy tools for size classification: 1) atrophic scars 2 to 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types; 2) atrophic scars \> 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types. Each type of atrophic acne scar was counted separately for each half-face by the evaluator for following regions: right forehead, right cheek, right side of the chin, left forehead, left cheek and left side of the chin. To obtain the total number of atrophic scars per half-face, atrophic acne scar counts for each half-face was added. |
Countries
Canada, France, United States
Participant flow
Recruitment details
The study was conducted at 20 sites in the United States, Canada, and France.
Pre-assignment details
A total 121 participants were enrolled in this study. All participants were randomized (left face versus right face) to apply trifarotene cream and trifarotene vehicle cream for an intra-individual, split-face comparison.
Participants by arm
| Arm | Count |
|---|---|
| All Acne Vulgaris Participants All participants applied a thin layer of trifarotene 50 mcg/g cream to half of their face and trifarotene vehicle cream to another half of their face topically once daily for up to 24 weeks. | 121 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 4 | 4 |
| Overall Study | Non-compliance with study drug | 1 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 13 | 13 |
Baseline characteristics
| Characteristic | All Acne Vulgaris Participants |
|---|---|
| Age, Continuous | 22.9 years STANDARD_DEVIATION 5.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fitzpatrick Skin Type Type I | 7 Participants |
| Fitzpatrick Skin Type Type II | 43 Participants |
| Fitzpatrick Skin Type Type III | 31 Participants |
| Fitzpatrick Skin Type Type IV | 26 Participants |
| Fitzpatrick Skin Type Type V | 11 Participants |
| Fitzpatrick Skin Type Type VI | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 97 Participants |
| Region of Enrollment Canada | 9 count of participants |
| Region of Enrollment France | 2 count of participants |
| Region of Enrollment United States | 110 count of participants |
| Sex: Female, Male Female | 88 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 121 | 0 / 121 | 0 / 121 |
| other Total, other adverse events | 7 / 121 | 3 / 121 | 33 / 121 |
| serious Total, serious adverse events | 0 / 121 | 0 / 121 | 0 / 121 |
Outcome results
Primary
Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half Face at Week 24
The scars were counted according to their size defined in two categories using 2 millimeter (mm) and 4 mm punch biopsy tools for size classification: 1) atrophic scars 2 to 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types; 2) atrophic scars greater than (\>) 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types. Each type of atrophic acne scar was counted separately for each half-face by the evaluator for following regions: right forehead, right cheek, right side of the chin, left forehead, left cheek and left side of the chin. To obtain the total number of atrophic scars per half-face, atrophic acne scar counts for each half-face was added.
Time frame: Baseline, Week 24
Population: ITT population included all randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trifarotene 50mcg/g Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half Face at Week 24 | -5.9 atrophic acne scars | Standard Error 0.51 |
| Trifarotene Vehicle Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half Face at Week 24 | -2.7 atrophic acne scars | Standard Error 0.37 |
p-value: <0.000195% CI: [-4.4, -2]Student's t-test for paired samples
Secondary
Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20
The scars were counted according to their size defined in two categories using 2 mm and 4 mm punch biopsy tools for size classification: 1) atrophic scars 2 to 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types; 2) atrophic scars \> 4 mm: included boxcar (sheer edges), rolling (irregular surface), and undetermined types. Each type of atrophic acne scar was counted separately for each half-face by the evaluator for following regions: right forehead, right cheek, right side of the chin, left forehead, left cheek and left side of the chin. To obtain the total number of atrophic scars per half-face, atrophic acne scar counts for each half-face was added.
Time frame: Baseline, up to Week 20
Population: ITT population included all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trifarotene 50mcg/g Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 4 | -1.5 atrophic acne scars | Standard Error 0.27 |
| Trifarotene 50mcg/g Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 12 | -3.8 atrophic acne scars | Standard Error 0.37 |
| Trifarotene 50mcg/g Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 2 | -0.9 atrophic acne scars | Standard Error 0.26 |
| Trifarotene 50mcg/g Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 16 | -4.4 atrophic acne scars | Standard Error 0.4 |
| Trifarotene 50mcg/g Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 8 | -2.5 atrophic acne scars | Standard Error 0.3 |
| Trifarotene 50mcg/g Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 20 | -5.0 atrophic acne scars | Standard Error 0.47 |
| Trifarotene 50mcg/g Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 1 | -0.3 atrophic acne scars | Standard Error 0.21 |
| Trifarotene Vehicle Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 20 | -2.5 atrophic acne scars | Standard Error 0.33 |
| Trifarotene Vehicle Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 1 | -0.3 atrophic acne scars | Standard Error 0.16 |
| Trifarotene Vehicle Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 2 | -0.4 atrophic acne scars | Standard Error 0.11 |
| Trifarotene Vehicle Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 4 | -0.7 atrophic acne scars | Standard Error 0.18 |
| Trifarotene Vehicle Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 8 | -1.1 atrophic acne scars | Standard Error 0.3 |
| Trifarotene Vehicle Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 12 | -1.7 atrophic acne scars | Standard Error 0.32 |
| Trifarotene Vehicle Cream | Absolute Change From Baseline in Total Atrophic Acne Scar Count Per Half-Face up to Week 20 | Change at Week 16 | -1.7 atrophic acne scars | Standard Error 0.47 |
Comparison: Week 1: Trifarotene 50 mcg/g, vehicle creamp-value: =0.947695% CI: [-0.3, 0.3]Student's t-test for paired samples
Comparison: Week 2: Trifarotene 50 mcg/g, vehicle creamp-value: =0.024895% CI: [-1.1, -0.1]Student's t-test for paired samples
Comparison: Week 4: Trifarotene 50 mcg/g, vehicle creamp-value: =0.007295% CI: [-1.4, -0.2]Student's t-test for paired samples
Comparison: Week 8: Trifarotene 50 mcg/g, vehicle creamp-value: <0.000195% CI: [-2.1, -0.7]Student's t-test for paired samples
Comparison: Week 12: Trifarotene 50 mcg/g, vehicle creamp-value: <0.000195% CI: [-2.9, -1.3]Student's t-test for paired samples
Comparison: Week 16: Trifarotene 50 mcg/g, vehicle creamp-value: <0.000195% CI: [-3.8, -1.6]Student's t-test for paired samples
Comparison: Week 20: Trifarotene 50 mcg/g, vehicle creamp-value: <0.000195% CI: [-3.5, -1.5]Student's t-test for paired samples