Phase I/II Randomized Placebo‑Controlled Dose‑Finding Study of Intramuscular MRT1800 mRNA Vaccine (Combination Therapy) in Adults 18–45 Years with Moderate‑to‑Severe Acne

Primary objectives focus on characterizing the investigational Acne mRNA vaccine. The study will assess the short‑term safety profile in sentinel cohorts, evaluate clinical efficacy in the main cohorts, and determine the long‑term safety of repeated dosing in the extension cohort, thereby establishing the tolerability and therapeutic potential of the vaccine for moderate to severe disease.

Secondary objectives include:

• Investigation of the longitudinal immune response to the vaccine antigens.
• Evaluation of efficacy durability over the study period.
• Additional assessment of the safety profile in the main cohorts.

The trial enrolled 360 participants who were identified as overtly healthy by medical history, physical examination, and laboratory testing. Eligible individuals were required to have a clinical diagnosis of moderate or severe facial acne vulgaris with an Investigator’s Global Assessment score of 3 or 4, at least 25 non‑inflammatory lesions, at least 20 inflammatory lesions, and no more than two nodulocystic lesions. Both female and male subjects were included, and the population comprised patients classified as vulnerable according to the protocol. The sponsor did not provide specific age‑range data for the enrolled cohort. Participants were otherwise healthy aside from their dermatologic condition, and no additional lifestyle restrictions or requirements were reported.

The study is a Phase I/II, randomized, placebo‑controlled, multi‑arm, dose‑finding trial evaluating the safety, efficacy and immunogenicity of an investigational mRNA vaccine in adults aged 18–45 with moderate to severe Acne. After a screening visit to confirm eligibility, participants are randomly assigned to receive either the vaccine (intramuscular suspension) or a 0.9 % sodium chloride placebo. Follow‑up visits are scheduled at defined intervals for vaccine administration, safety assessments, lesion counts, Investigator’s Global Assessment, and collection of serum for antibody titers, concluding with an end‑of‑study visit that captures final safety and efficacy outcomes. Participant involvement extends from the screening visit through the end‑of‑study visit, with the overall trial period spanning from 24 August 2026 to 21 December 2026. Early termination may occur if a participant experiences a serious adverse event, meets predefined discontinuation criteria, or withdraws consent.

The investigational product, designated as the Acne mRNA vaccine, is supplied as a suspension for injection and contains the active mRNA sequences MRT1800, MRT1801, and MRT1802. It is administered by intramuscular injection. The specific dose amount, volume, and frequency of administration are defined in the study protocol and are applied uniformly to participants assigned to the test arm.

The control comparator consists of a diluent containing 0.9 % sodium chloride solution. This placebo is provided without active pharmaceutical ingredients and is administered by the same intramuscular route as the investigational vaccine, matching the volume and administration schedule of the active product.

All study injections are performed by qualified personnel under aseptic conditions. Participants are observed for a predefined period after each administration to monitor immediate safety. Dosing schedules may include multiple administrations according to the protocol-defined timeline. Compliance with the dosing regimen is documented in the study record, and participants maintain a dosing diary to record each injection and any related observations.

Efficacy assessment will focus on changes in facial lesion counts associated with Acne. Primary efficacy parameters include the percentage change from baseline (Day 1) in the number of inflammatory lesions, the percentage change in non‑inflammatory lesions, and the percentage change in the total number of lesions on the face. Secondary efficacy parameters comprise absolute and percentage changes from baseline in the total lesion count, absolute and percentage changes in inflammatory and non‑inflammatory lesion numbers, and the absolute change from baseline in the IGA score. An additional secondary endpoint is the assessment of vaccine‑antigen‑specific serum antibody titers.

Lesion counts will be performed by trained investigators using standardized counting procedures. The IGA score will be assigned according to a validated global assessment scale. Serum antibody concentrations will be measured with a validated immunoassay. All efficacy parameters will be derived by comparing values obtained at post‑baseline visits with the baseline (Day 1) measurements.