Acne
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALAcne mRNA vaccine
Pharmaceutical form: Liquid suspension for injection Route of administration: intramuscular
OTHERPlacebo
Pharmaceutical form: Liquid solution for injection Route of administration: intramuscular
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Core Study - Sentinel Cohorts A and B: Number of participants with unsolicited systemic AEs | 30 minutes after each administration | Presence of unsolicited systemic adverse events (AEs) reported |
| Core Study - Sentinel Cohorts A and B: Number of participants with solicited injection site and systemic reactions | Up to 7 days after each administration | Presence of solicited injection site and systemic reactions (ie, pre-listed in the participant diary \[PDi\] and in the case report form \[CRF\]) |
| Core Study - Sentinel Cohorts A and B: Number of participants with unsolicited AEs | Up to 28 days after each administration | — |
| Core Study - Sentinel Cohorts A and B: Number of participants with MAAEs | Up to 6 months after each administration | Presence of medically attended adverse events (MAAEs) |
| Core Study - Sentinel Cohorts A and B: Number of participants with SAEs | Up to 6 months after each administration | Presence of all serious adverse events (SAEs) |
| Core Study - Sentinel Cohorts A and B: Number of participants with AESIs | Up to 6 months after each administration | Presence of AEs of special interest (AESIs) |
| Core Study - Sentinel Cohorts A and B: Number of participants with out-of-range biological test results (including shift from baseline values) | Through 7 days after administration (Day 8) | — |
| Core Study - Main Cohort A: Percentage change from baseline (Day 1) in the number of inflammatory acne lesions on face | At 2 months post last administration | — |
| Core Study - Main Cohort A: Percentage change from baseline (Day 1) in the number of non-inflammatory acne lesions on face | At 2 months post last administration | — |
| Core Study - Main Cohort B: Percentage change from baseline (Day 1) in the total number of acne lesions on face at | At 2 months post last administration | — |
| Long-Term Extension - Sentinel Cohorts A, B and Main Cohort: Number of participants with SAEs and AESIs | Up to 38 or 40 months after first administration | Presence of all serious adverse events (SAEs) and adverse events of special interest (AESIs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Core Study - Sentinel Cohorts A, B and Main Cohorts A and B: Assessment of accine-antigen-specific serum antibody titers | From baseline (Day 1) to 6 months post last administration | — |
| Core Study - Main Cohort B: Absolute change from baseline (Day 1) in the total number of inflammatory acne lesions on face | At 1 month post first administration until 9 months post last administration | — |
| Core Study - Main Cohorts A and B: Percentage change from baseline (Day 1) in the number of inflammatory acne lesions on face | At 1 month post first administration until 6 or 9 months post last administration | — |
| Core Study - Main Cohorts A and B: Absolute change from baseline (Day 1) in the number of non-inflammatory acne lesions on face | At 1 month post first administration until 6 or 9 months post last administration | — |
| Core Study - Main Cohorts A and B: Absolute change from baseline in IGA score | At 1 month post first administration until 6 or 9 months post last administration | — |
| Core Study - Main Cohorts A and B: Number of participants with unsolicited systemic AEs | 30 minutes after each administration | Presence of unsolicited systemic adverse events (AEs) reported |
| Core Study - Main Cohorts A and B: Number of participants with solicited injection site and systemic reactions | Up to 7 days after each administration | Presence of solicited injection site and systemic reactions (ie, pre-listed in the participant diary \[PDi\] and in the case report form \[CRF\]) |
| Core Study - Main Cohorts A and B: Number of participants with unsolicited AEs | Up to 28 days after each administration | — |
| Core Study - Main Cohorts A and B: Number of participants with MAAEs | Up to 6 or 9 months after each administration | Presence of medically attended adverse events (MAAEs) |
| Core Study - Main Cohorts A and B: Number of participants with SAEs | Up to 6 or 9 months after each administration | Presence of all serious adverse events (SAEs) |
| Core Study - Main Cohorts A and B: Number of participants with AESIs | Up to 6 or 9 months after each administration | Presence of AEs of special interest (AESIs) |
| Core Study - Main Cohorts A and B: Number of participants with out-of-range biological test results (including shift from baseline values) | Up to 7 days after each administration | — |
Countries
Australia, Canada, Puerto Rico, United States
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed