Acne Vulgaris
Conditions
Brief summary
The purpose of this study was to demonstrate that daily use of topical trifarotene (CD5789) 50 microgram per gram (mcg/g) cream when used in association with oral antibiotic is safe and effective for the treatment of severe AV.
Interventions
Trifarotene 50 mcg/g cream applied topically once daily on face for 12 weeks.
Doxycycline hyclate delayed release 120 mg tablets was administered orally for 12 weeks.
DRUGTrifarotene Vehicle
Trifarotene 50 mcg/g vehicle cream was applied topically once daily on face for 12 weeks.
DRUGDoxycycline Placebo
Doxycycline hyclate delayed release 120 mg placebo tablets was administered orally for 12 weeks.
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with clinical diagnosis of acne vulgaris, defined by IGA score of 4 (Severe) * Participants with at least 20 inflammatory lesions (papules and pustules) and 30 to 120 non-inflammatory lesions (open comedones and closed comedones) and no more than 2 nodules (less than \[\<\]1 centimeter \[cm\] in diameter) on the face, excluding the nose * Agrees to provide written informed consent * Participant is a female of non-childbearing potential (premenarchal or postmenopausal \[absence of menstrual bleeding for 1 year prior to Screening, without any other medical reason\], hysterectomy or bilateral oophorectomy)
Exclusion criteria
* Participant with any acne cyst on the face * Participants with nodulocystic or conglobate acne, acne fulminans, or secondary acne (chloracne, drug-induced acne, etc.) * Participants with facial dermal conditions (example \[e.g.\] tattoo, skin abrasion, eczema, sunburned skin, scars, nevi, etc.) that may interfere with study assessments in the opinion of the investigator * Participants who is at risk in terms of precautions, warnings, and contraindications for trifarotene or doxycycline hyclate * Currently receiving any prescription testosterone therapy (e.g., testosterone cypionate, testosterone enanthate, testosterone pellet, testosterone undecanoate) or on a testosterone booster or prescription testosterone (e.g., dehydroepiandrosterone \[DHEA\], Omnadren, Sustanon, testosterone cypionate, testosterone enanthate, testosterone propionate, testosterone phenylpropionate) or testosterone supplements (e.g., Tribulus).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Facial Total Lesion Counts to Week 12 | From Baseline to Week 12 | Total lesion counts corresponded to the sum of inflammatory and non-inflammatory lesions, and papules. The investigator (or subinvestigator) counted all inflammatory lesions (papules, pustules, and nodular lesions) and non-inflammatory lesions (open and closed comedos; diagnosis based on palpation) on the face. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Facial Inflammatory Lesions (IL) Counts to Week 12 | From Baseline to Week 12 | All inflammatory lesions (papules, pustules, and nodular lesions) were counted by investigator/subinvestigator. |
| Absolute Change From Baseline in Facial Non Inflammatory Lesions (NIL) Counts to Week 12 | From Baseline to Week 12 | Non-inflammatory lesions (open and closed comedo) were counted by investigator/subinvestigator. |
| Percentage of Participants Who Achieved an IGA Score of 1 (Almost Clear) or 0 (Clear) and At Least a 2-Grade Improvement From Baseline to Week 12 | From Baseline to Week 12 | IGA was an assessment scale used to evaluate facial acne severity. IGA was recorded from components collected on the case report form (CRF) using a 5-point scale where (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on inflammation, pustules and papulation/infiltration. Success Rate was defined as the percentage of participants who achieved an IGA score of 1 (Almost Clear) or 0 (Clear) and at least a 2-grade improvement from Baseline to Week 12. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Study was conducted at United States of America and Puerto Rico between 29 Jul 2020 and 26 Apr 2021.
Pre-assignment details
A total of 202 participants were randomized in 2:1 ratio in 2 treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Trifarotene + Doxycycline Participants were applied with Trifarotene (CD5789) 50 micrograms per gram (mcg/g) cream topically on the face once daily in the evening for 12 weeks and received doxycycline 120 milligrams (mg) tablet orally once daily in the evening and 1 tablet in the morning on Day 2 of every week for 12 weeks. | 133 |
| Trifarotene Vehicle + Doxycycline Placebo Participants were applied with vehicle CD5789 topically on the face once daily in the evening for 12 weeks and received doxycycline matching placebo tablet orally once daily in the evening and 1 tablet in the morning on Day 2 of every week for 12 weeks. | 69 |
| Total | 202 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Lost to Follow-up | 5 | 0 |
| Overall Study | Other than specified | 0 | 1 |
| Overall Study | Withdrawal by parent/guardian | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Trifarotene + Doxycycline | Trifarotene Vehicle + Doxycycline Placebo | Total |
|---|---|---|---|
| Age, Continuous | 20.0 years STANDARD_DEVIATION 7.3 | 20.3 years STANDARD_DEVIATION 8.92 | 20.1 years STANDARD_DEVIATION 7.87 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 50 Participants | 20 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 83 Participants | 49 Participants | 132 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Facial Total Lesions Counts | 101.5 Lesion counts STANDARD_DEVIATION 40.11 | 100.7 Lesion counts STANDARD_DEVIATION 33.91 | 101.2 Lesion counts STANDARD_DEVIATION 38.02 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 6 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 114 Participants | 58 Participants | 172 Participants |
| Sex: Female, Male Female | 80 Participants | 43 Participants | 123 Participants |
| Sex: Female, Male Male | 53 Participants | 26 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 133 | 0 / 69 |
| other Total, other adverse events | 0 / 133 | 0 / 69 |
| serious Total, serious adverse events | 1 / 133 | 0 / 69 |
Outcome results
Primary
Absolute Change From Baseline in Facial Total Lesion Counts to Week 12
Total lesion counts corresponded to the sum of inflammatory and non-inflammatory lesions, and papules. The investigator (or subinvestigator) counted all inflammatory lesions (papules, pustules, and nodular lesions) and non-inflammatory lesions (open and closed comedos; diagnosis based on palpation) on the face.
Time frame: From Baseline to Week 12
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Trifarotene + Doxycycline | Absolute Change From Baseline in Facial Total Lesion Counts to Week 12 | -69.1 Lesion counts | Standard Deviation 2.28 |
| Trifarotene Vehicle + Doxycycline Placebo | Absolute Change From Baseline in Facial Total Lesion Counts to Week 12 | -48.1 Lesion counts | Standard Deviation 3.14 |
Secondary
Absolute Change From Baseline in Facial Inflammatory Lesions (IL) Counts to Week 12
All inflammatory lesions (papules, pustules, and nodular lesions) were counted by investigator/subinvestigator.
Time frame: From Baseline to Week 12
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Trifarotene + Doxycycline | Absolute Change From Baseline in Facial Inflammatory Lesions (IL) Counts to Week 12 | -29.4 Lesion counts | Standard Error 1.09 |
| Trifarotene Vehicle + Doxycycline Placebo | Absolute Change From Baseline in Facial Inflammatory Lesions (IL) Counts to Week 12 | -19.5 Lesion counts | Standard Error 1.49 |
Secondary
Absolute Change From Baseline in Facial Non Inflammatory Lesions (NIL) Counts to Week 12
Non-inflammatory lesions (open and closed comedo) were counted by investigator/subinvestigator.
Time frame: From Baseline to Week 12
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Trifarotene + Doxycycline | Absolute Change From Baseline in Facial Non Inflammatory Lesions (NIL) Counts to Week 12 | -39.5 Lesion counts | Standard Deviation 1.42 |
| Trifarotene Vehicle + Doxycycline Placebo | Absolute Change From Baseline in Facial Non Inflammatory Lesions (NIL) Counts to Week 12 | -28.2 Lesion counts | Standard Deviation 1.96 |
Secondary
Percentage of Participants Who Achieved an IGA Score of 1 (Almost Clear) or 0 (Clear) and At Least a 2-Grade Improvement From Baseline to Week 12
IGA was an assessment scale used to evaluate facial acne severity. IGA was recorded from components collected on the case report form (CRF) using a 5-point scale where (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on inflammation, pustules and papulation/infiltration. Success Rate was defined as the percentage of participants who achieved an IGA score of 1 (Almost Clear) or 0 (Clear) and at least a 2-grade improvement from Baseline to Week 12.
Time frame: From Baseline to Week 12
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trifarotene + Doxycycline | Percentage of Participants Who Achieved an IGA Score of 1 (Almost Clear) or 0 (Clear) and At Least a 2-Grade Improvement From Baseline to Week 12 | 31.7 percentage of participants |
| Trifarotene Vehicle + Doxycycline Placebo | Percentage of Participants Who Achieved an IGA Score of 1 (Almost Clear) or 0 (Clear) and At Least a 2-Grade Improvement From Baseline to Week 12 | 15.8 percentage of participants |