The purpose of the trial is to evaluate the safety, efficacy and immunogenicity of up to 3 intramuscular injections of the Acne mRNA vaccine candidate at up to four dose levels in adult participants aged 18 to 45 years with moderate to severe acne.

This trial will consist of a Core Study followed by an optional Long-Term Extension (LTE).

The Core Study will consist of:

• Two cohorts evaluating the 2-administration regimen (Cohorts A): Sentinel Cohort A and Main Cohort A.
• Two cohorts evaluating the 3-administration regimen (Cohorts B): Sentinel Cohort B and Main Cohort B.

Participants from Sentinel Cohorts A and B and from Main Cohort A will be invited to an additional 30-month follow up after completing their last planned Core Study visit to assess the long-term effects of the vaccine. Participants from Main Cohort B will be invited to another LTE study managed through a separate protocol.

Acne vulgaris (acne) is a highly prevalent inflammatory skin disease, especially in adolescents and young adults. Acne is estimated to affect 231 million people worldwide, therefore being one of the most prevalent diseases globally. Acne is also one of the top causes of years lived with disability and nonfatal disease burden. Despite being one of the most prevalent diseases worldwide, the mainstays of acne treatment have remained largely unchanged over the past 30 years. To date there is still no safe and effective treatment that can prevent and cure this disease.

The aim of this first-in-human (FIH), Phase I/II trial is to evaluate the safety, efficacy and immunogenicity of the Acne mRNA vaccine candidate at four different dose levels in adults aged 18 to 45 years with moderate to severe acne. The results of this FIH and proof of concept study will allow selection of the vaccine dose level to be used in Phase III pivotal efficacy trial(s) and to generate preliminary data to further select the vaccine regimen.

Inclusion Criteria:

• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests as judged by the investigator
• Clinical diagnosis of moderate or severe facial acne vulgaris with Investigator's Global Assessment (IGA) score of Moderate or Severe (grade 3 or grade 4 on the 5-grade IGA scale) and ≥ 25 non-inflammatory lesions (ie, open and closed comedones) and ≥ 20 inflammatory lesions (ie, papules and pustules) and ≤ 2 nodulocystic lesions (ie, nodules and cysts)

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within 6 months prior to the first study intervention administration; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Known systemic hypersensitivity to any of the study intervention components; history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances; any allergic reaction (eg, anaphylaxis) after administration of mRNA coronavirus disease 2019 (COVID-19) vaccine
• Active nodulocystic acne, acne conglobate, acne fulminans, secondary acne (eg, chloracne, drug-induced acne) or other forms of acne (eg, acne mechanica)
• Use of any acne-affecting treatment without an appropriate washout period
• Receipt of any vaccine (other than the study vaccine) in the 4 weeks preceding any study intervention administration or planned receipt of any vaccine (other than the study vaccine) in the 4 weeks following any study intervention administration
• Previous vaccination against C. acnes with an investigational vaccine
• Receipt of immune globulins, blood or blood-derived products in the past 3 months
• Self-reported or documented seropositivity for human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Core Study:

Sentinel Cohorts: modified double-blind

• Investigators, participants, laboratory personnel will be blinded.
• Clinical site staff preparing/administering the study vaccines will be unblinded.
• Sponsor study staff involved in ESDRs will be unblinded at the time of the ESDR.

Main Cohorts: modified double-blind

• Investigators, participants, laboratory personnel and Sponsor study staff will be blinded.
• Only clinical site staff preparing/administering the study vaccines will be unblinded.
• Sponsor staff involved in the Internal Firewall Committee will be unblinded at the time of interim analyses.

Long-Term Extension:

Sentinel Cohorts and Main Cohorts: double-blind

• Investigators, participants, laboratory personnel and Sponsor study staff will be blinded.
• Sponsor staff involved in the Internal Firewall Committee will be unblinded at the time of interim analyses.