A Phase I/II, Randomized, Placebo-controlled, Multi-arm, Dose-finding Study to Evaluate the Safety, Efficacy and Immunogenicity of an Acne mRNA Vaccine Candidate in Adults With Moderate to Severe Acne 18 to 45 Years of Age
Overview
- Phase
- Phase 1
- Intervention
- Acne mRNA vaccine
- Conditions
- Acne
- Sponsor
- Sanofi Pasteur, a Sanofi Company
- Enrollment
- 260
- Locations
- 93
- Primary Endpoint
- Core Study - Sentinel Cohort A and B: Number of participants with unsolicited systemic AEs
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
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 three 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 a Sentinel Cohort A paired with a Main Cohort, evaluating the safety and efficacy of the 2-administration regimen and a Sentinel Cohort B, evaluating the safety of the 3- administration regimen. The Sentinel Cohorts will assess the safety of the dose levels and regimens in a stepwise manner. If the participants consent to the LTE, they will be followed up for an additional 30 months after the last planned visit in the Core Study, to assess the long-term effects of the vaccine.
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 three 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.
Investigators
Eligibility Criteria
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 (eg, polyethylene glycol \[PEG\], polysorbate); 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.
Arms & Interventions
Sentinel Cohort A - Experimental
Two administrations of the Acne mRNA vaccine will be injected in three increasing doses
Intervention: Acne mRNA vaccine
Sentinel Cohort A - Placebo
Two administrations of placebo will be injected
Intervention: Placebo
Sentinel Cohort B - Experimental
Three administrations of the Acne mRNA vaccine will be injected in two increasing doses
Intervention: Acne mRNA vaccine
Sentinel Cohort B - Placebo
Three administrations of placebo will be injected
Intervention: Placebo
Main Cohort - Experimental
Two administrations of the Acne mRNA vaccine will be injected in three increasing doses
Intervention: Acne mRNA vaccine
Main Cohort - Placebo
Two administrations of placebo will be injected
Intervention: Placebo
Outcomes
Primary Outcomes
Core Study - Sentinel Cohort A and B: Number of participants with unsolicited systemic AEs
Time Frame: 30 minutes after each administration
Presence of unsolicited systemic adverse events (AEs) reported
Core Study - Sentinel Cohort A and B: Number of participants with solicited injection site and systemic reactions
Time Frame: 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 Cohort A and B: Number of participants with unsolicited AEs
Time Frame: Up to 28 days after each administration
Core Study - Sentinel Cohort A and B: Number of participants with MAAEs
Time Frame: Up to 6 months after each administration
Presence of medically attended adverse events (MAAEs)
Core Study - Sentinel Cohort A and B: Number of participants with SAEs
Time Frame: Up to 6 months after each administration
Presence of all serious adverse events (SAEs)
Core Study - Sentinel Cohort A and B: Number of participants with AESIs
Time Frame: Up to 6 months after each administration
Presence of AEs of special interest (AESIs)
Core Study - Sentinel Cohort A and B: Number of participants with out-of-range biological test results (including shift from baseline values)
Time Frame: Through 7 days after administration (Day 8)
Core Study - Main Cohort: Percentage change from baseline (Day 1) in the number of inflammatory acne lesions on face
Time Frame: At 2 months post last administration
Core Study - Main Cohort: Percentage change from baseline (Day 1) in the number of non-inflammatory acne lesions on face
Time Frame: At 2 months post last administration
Long-Term Extension - Sentinel Cohort A, B and Main Cohort: Number of participants with SAEs and AESIs
Time Frame: Up to 38 months after first administration
Presence of all serious adverse events (SAEs) and adverse events of special interest (AESIs)
Secondary Outcomes
- Core Study - Sentinel Cohort A, B and Main Cohort: Vaccine-antigen-specific serum antibody titers(From baseline (Day 1) to 6 months post last administration)
- Core Study - Main Cohort: Absolute change from baseline (Day 1) in the number of inflammatory acne lesions on face(At1 month post first administration until 6 months post last administration)
- Core Study - Main Cohort: Percentage change from baseline (Day 1) in the number of inflammatory acne lesions on face(At 1 month post first administration until 6 months post last administration)
- Core Study - Main Cohort: Absolute change from baseline (Day 1) in the number of non-inflammatory acne lesions on face(At 1 month post first administration until 6 months post last administration)
- Core Study - Main Cohort: Percentage change from baseline (Day 1) in the number of non-inflammatory acne lesions on face(At 1 month post first administration until 6 months post last administration)
- Core Study - Main Cohort: Absolute change from baseline in IGA score(At 1 month post first administration until 6 months post last administration)
- Core Study - Main Cohort: Number of participants with unsolicited systemic AEs(30 minutes after each administration)
- Core Study - Main Cohort: Number of participants with solicited injection site and systemic reactions(Up to 7 days after each administration)
- Core Study - Main Cohort: Number of participants with unsolicited AEs(Up to 28 days after each administration)
- Core Study - Main Cohort: Number of participants with MAAEs(Up to 6 months after each administration)
- Core Study - Main Cohort: Number of participants with SAEs(Up to 6 months after each administration)
- Core Study - Main Cohort: Number of participants with AESIs(Up to 6 months after each administration)
- Core Study - Main Cohort: Number of participants with out-of-range biological test results (including shift from baseline values)(Through 7 days after administration (Day 8))