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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 800
- 试验地点
- 187
- 主要终点
- Core Study - Sentinel Cohort A and B: Number of participants with unsolicited systemic AEs
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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.
研究组 & 干预措施
Main Cohort B - Placebo
Three administrations of placebo will be injected
干预措施: Placebo (Other)
Main Cohort - Experimental
Two administrations of the Acne mRNA vaccine will be injected in three increasing doses
干预措施: Acne mRNA vaccine (Biological)
Sentinel Cohort B - Experimental
Three administrations of the Acne mRNA vaccine will be injected in two increasing doses
干预措施: Acne mRNA vaccine (Biological)
Main Cohort A - Experimental
Two administrations of the Acne mRNA vaccine will be injected in three increasing doses
干预措施: Acne mRNA vaccine (Biological)
Main Cohort B - Experimental
Three administrations of the Acne mRNA vaccine will be injected in two increasing doses
干预措施: Acne mRNA vaccine (Biological)
Sentinel Cohort A - Experimental
Two administrations of the Acne mRNA vaccine will be injected in three increasing doses
干预措施: Acne mRNA vaccine (Biological)
Sentinel Cohort B - Placebo
Three administrations of placebo will be injected
干预措施: Placebo (Other)
Main Cohort A - Placebo
Two administrations of placebo will be injected
干预措施: Placebo (Other)
Sentinel Cohort A - Placebo
Two administrations of placebo will be injected
干预措施: Placebo (Other)
结局指标
主要结局
Core Study - Sentinel Cohort A and B: Number of participants with unsolicited systemic AEs
时间窗: 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
时间窗: 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
时间窗: Up to 28 days after each administration
Core Study - Sentinel Cohort A and B: Number of participants with MAAEs
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: At 2 months post last administration
Long-Term Extension - Sentinel Cohort A, B and Main Cohort: Number of participants with SAEs and AESIs
时间窗: Up to 38 months after first administration
Presence of all serious adverse events (SAEs) and adverse events of special interest (AESIs)
次要结局
- 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))