Evaluation of Oral Isotretinoin Versus Standard Care in Moderate Acne Among Skin of Color Patients: A Randomized Clinical Trial

The primary objective of this randomized clinical trial is to assess the **superiority** of early treatment with oral isotretinoin over the current standard of care in reducing the severity of moderate facial acne in skin of color patients after six months. This is clinically relevant as it aims to establish a more effective treatment protocol for a demographic that may experience different responses to acne treatments.

Secondary objectives include:

• Comparing the efficacy of isotretinoin versus standard care in patients with varying baseline acne severity, specifically those with no or very mild acne-related problems (ARP score <2) and those with more severe conditions (ARP score ≥2).
• Evaluating the efficacy of early isotretinoin treatment compared to standard care on retentional and inflammatory acne lesions after three and six months.
• Assessing the tolerance of the treatment protocols in patients with skin of color.
• Monitoring the evolution of the quality of life in patients receiving early isotretinoin treatment compared to standard care throughout the study period.

The clinical trial focuses on evaluating the effectiveness of early treatment for **moderate facial acne** in individuals with skin of color using oral isotretinoin compared to the current standard of care. The study population comprises both **women and men** aged between 13 and 30 years, with skin types IV, V, and VI as per the Fitzpatrick classification. Participants are required to have moderate acne, as defined by the French Society of Dermatology recommendations. The trial includes individuals who possess a cell phone capable of taking selfies with a minimum resolution of 5Mb. Participants must be affiliated with French social coverage and have provided signed informed consent. The sponsor has not provided information regarding the total number of participants. The trial population includes both genders and is considered a vulnerable population. The selection criteria emphasize the importance of specific skin types and technological capabilities, reflecting the study's focus on a particular demographic and lifestyle considerations.

The clinical trial is designed to evaluate the efficacy of oral **isotretinoin** compared to the standard of care in patients with moderate acne, specifically targeting individuals with skin of color. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thus minimizing bias. The trial is set to commence on April 29, 2025, with an estimated completion date of March 1, 2027, spanning a total duration of approximately 22 months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, skin type, and acne severity. The inclusion criteria specify that participants must be between 13 and 30 years old, have skin types IV, V, or VI according to the Fitzpatrick scale, and present with moderate acne as per the French Society of Dermatology recommendations. Following the screening, participants will be randomly assigned to receive either oral isotretinoin or the standard treatment. The trial includes follow-up visits at three months (M3) and six months (M6) to assess the primary endpoint, which is the severity of acne-related pigmentation (ARP) using a validated algorithm on facial selfies. Secondary endpoints include subgroup efficacy, lesion count, adverse events, scarring, and quality of life assessments.

The expected length of participant involvement is up to six months, with conditions for early termination including significant adverse events or withdrawal of consent. The trial aims to provide robust data on the effectiveness of early isotretinoin treatment in reducing acne severity and improving quality of life in the target population. Participants' progress will be closely monitored throughout the study, with data collected at each visit to ensure comprehensive evaluation of the treatment's impact.

The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. The primary experimental medication is **PROCUTA**, which is available in three different dosages: 10 mg, 20 mg, and 40 mg, all in the form of soft capsules. The active substance in PROCUTA is **isotretinoin**, a chemical compound. The medication is administered orally with a maximum daily dose of 0.5 mg/kg for the 10 mg and 40 mg capsules, and 0.25 mg/kg for the 20 mg capsule. The maximum total dose is 150 mg/kg over a treatment period of up to 6 months. Participant compliance is monitored through regular assessments to ensure adherence to the dosing schedule.

In addition to the experimental treatment, the study includes several non-experimental treatments. **DIFFERINE 0.1% cream**, containing the active substance **adapalene**, is applied cutaneously. The maximum daily dose is 0.3 g, with a total dose not exceeding 60 g over a 6-month period. **EFFEDERM 0.05% cream**, with **tretinoin** as the active ingredient, is also applied cutaneously under the same dosing conditions as DIFFERINE. Another non-experimental treatment is **ADAPALENE ZENTIVA 0.1% cream**, which also contains adapalene and follows the same dosing regimen as DIFFERINE and EFFEDERM.

Additional non-experimental treatments include **Doxycycline EG 100 mg tablets**, administered orally with a maximum daily dose of 100 mg and a total dose of 9 g over a 3-month period. **LYMECYCLINE ARROW 408 mg capsules**, equivalent to 300 mg of tetracycline base, are also administered orally with the same dosing schedule as doxycycline. These non-experimental treatments serve as comparator treatments to evaluate the efficacy of the experimental medication in the context of moderate acne in patients with skin of color.

The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is the **ARP severity score**, which will be evaluated using a dedicated algorithm on facial pictures (selfies) at month 6 (M6). This algorithm, validated for assessing hyperpigmented lesions in dark skin types, provides a score ranging from 0 (no ARP) to 4 (severe ARP). A successful outcome is defined as a patient achieving a score of less than 2 at M6, indicating no or very mild ARP.

Secondary endpoints include the evaluation of efficacy in subgroups at M6, with subgroups defined by initial ARP severity. The inflammatory and retentional lesions count will be assessed at 3 months (M3) and M6 using the same algorithm on selfies, with comparisons made to baseline values. Additionally, the evolution of these lesions will be clinically assessed using the GEA scale grading. Adverse events will be documented, focusing on scars using the IGA score, and the ADRS will be performed for adolescents at each visit. Quality of life will be measured using the Acne-specific Quality of Life questionnaire (Acne-QoL).