A phase 2 randomized, double blind, placebo-controlled study to evaluate the safety and efficacy of topical AT-004 1% in the participants with acne vulgaris.

The primary objectives of this study are to evaluate the safety and tolerability of topically administered AT-004 in adults with acne vulgaris, to assess therapeutic efficacy using the Investigator Global Assessment (IGA) at week 8, and to quantify changes in the number of inflammatory and non-inflammatory lesions at week 8. These primary endpoints are clinically relevant as they establish the fundamental safety profile of the investigational agent while simultaneously measuring objective clinical improvement through validated assessment tools and lesion counts, which are standard efficacy parameters in acne clinical trials.

The secondary objectives include:

• Evaluation of efficacy using IGA scores at weeks 4 and 12 to assess the temporal pattern of therapeutic response

• Assessment of inflammatory and non-inflammatory lesion counts at weeks 4 and 12 to characterize the time course of clinical improvement

• Measurement of health-related quality of life in participants receiving topical AT-004 to evaluate the psychosocial impact of treatment

• Characterization of pharmacokinetic parameters following topical administration of AT-004 to determine systemic exposure and absorption characteristics

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population consisted of adults with **acne vulgaris**, with participants ranging from **18 to 45 years of age**. Both **male and female subjects** were included in the trial. Participants were required to present with mild, moderate, or severe facial acne, defined as an **Investigator Global Assessment (IGA)** score of 2 or higher, along with a minimum of 10 **inflammatory lesions** and 15 **non-inflammatory lesions** on the face at baseline. General health status required individuals to be in sufficient medical health to participate safely in the trial. Female participants of childbearing potential were required to use effective **contraception** methods from enrollment through at least 3 months post-study, while sexually active male participants with female partners of childbearing potential were required to use condoms during the same period. Male participants were additionally required to maintain either a clean-shaven appearance or a neatly trimmed beard to ensure proper study assessments. The trial population was selected based on these specific clinical and demographic criteria to ensure appropriate evaluation of the investigational product's safety and efficacy.

This is a **Phase 2**, **randomized**, **double-blind**, **placebo-controlled** clinical trial designed to evaluate the safety and efficacy of topical **AT-004 1%** cream containing **donepezil hydrochloride** in adult participants with **acne vulgaris**. The study employs a controlled design in which participants will be randomly assigned to receive either the active investigational medicinal product or a matched placebo. The **double-blind** methodology ensures that neither participants nor investigators are aware of treatment allocation during the conduct of the trial. The investigational product will be administered via **topical application** at a maximum daily dose of **20 mg**, with a maximum total dose of **1680 mg** over a treatment period of **12 weeks**.

The primary objectives of this trial are to assess the safety and tolerability of AT-004 when administered topically to adults with acne vulgaris, and to evaluate efficacy using the **Investigator Global Assessment (IGA)** score at week 8, as well as changes in the absolute number of **inflammatory lesions** and **noninflammatory lesions** at week 8. Secondary endpoints include the proportion of treatment successes according to IGA scores at weeks 4 and 12, absolute and percent changes in lesion counts at multiple time points, pharmacokinetic evaluation in a subset of participants, and assessment of quality of life using the **Dermatology Life Quality Index (DLQI)**. Safety will be monitored through the recording of **adverse events**, laboratory safety parameters, vital signs, physical examination findings, body weight, and **skin reactions** at the application site.

Eligible participants must be between 18 and 45 years of age and present with mild, moderate, or severe facial acne defined as an IGA score of 2 or higher at both screening and baseline visits. At baseline, participants must have at least 10 inflammatory lesions and at least 15 noninflammatory lesions on the face. Female participants of childbearing potential must use an acceptably effective method of contraception from enrollment until at least 3 months after study completion, and sexually active male participants with female partners of childbearing potential must agree to use condoms during the same period. Male participants must maintain either a clean-shaven appearance or a neatly trimmed beard that does not interfere with study assessments throughout the treatment period. Participants must be willing to comply with all study procedures, including having photographs taken of their acne at baseline and at follow-up visits at weeks 4, 8, and 12.

The study consists of a structured series of visits beginning with a screening visit to assess eligibility and baseline disease characteristics. Following successful screening, participants will attend a baseline visit (Visit 1) where treatment will be initiated. Follow-up visits are scheduled at week 4, week 8, and week 12 to assess efficacy endpoints, monitor safety parameters, and evaluate changes in lesion counts and quality of life measures. The end-of-study visit occurs at week 12, marking the completion of the treatment period. The total duration of participant involvement in the trial is approximately 12 weeks from baseline to the final assessment. Participants may be withdrawn from the study early if they experience intolerable adverse events, fail to comply with study procedures, withdraw consent, or if the investigator determines that continued participation is not in the participant's best interest. The estimated recruitment start date is November 2025, with an estimated study completion date of July 2026.

The experimental medication **AT-004** is formulated as a **cream** containing **donepezil hydrochloride** as the active substance. The pharmaceutical form is a topical cream administered via **topical application** to the affected skin areas. The maximum daily dose is **20 mg**, with a maximum total dose of **1680 mg** over the treatment period. The treatment duration extends for **12 weeks**. AT-004 is manufactured by Arctic Therapeutics ehf. and is identified by the sponsor product code AT-004. The active substance, donepezil hydrochloride, is a chemical entity also known as 2-[(1-benzyl-4-piperidyl)methyl]-5,6-dimethoxy-2,3-dihydroinden-1-one hydrochloride.

The **placebo** comparator is formulated as a matched placebo for the investigational medicinal product. This placebo is designed to match the experimental medication in appearance and administration characteristics to maintain the integrity of the double-blind study design. The placebo does not contain any active pharmaceutical ingredient and serves as the control treatment arm in this randomized, placebo-controlled clinical trial.

Efficacy will be assessed through multiple parameters evaluating both clinical improvement and quality of life outcomes in participants with acne vulgaris. The primary efficacy endpoints include the proportion of treatment successes according to Investigator Global Assessment (IGA) score at week 8, absolute change in the number of inflammatory lesions at week 8, and absolute change in the number of noninflammatory lesions at week 8. Secondary efficacy endpoints will evaluate the proportion of successes according to IGA score at weeks 4 and 12, absolute change in the number of inflammatory and noninflammatory lesions at weeks 4 and 12, and percent change in the number of inflammatory and noninflammatory lesions at weeks 4, 8, and 12. Additional secondary endpoints include change in Dermatology Life Quality Index (DLQI) score from baseline to weeks 4, 8, and 12, as well as the proportion of participants achieving a reduction in DLQI of greater than 4 points from baseline to weeks 8 and 12 among those with baseline DLQI greater than 4. Pharmacokinetic parameters of AT-004 will be established in a subset of 5 participants.