Phase I/IIa Clinical Trial to Evaluate the Safety and Immunogenicity of StreptInCor, a Synthetic Vaccine Against Streptococcus Pyogenes, in Healthy Adult Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Safety outcome
研究概览
简要总结
This is a Phase I/IIa, randomized, double-blind, placebo-controlled, dose-escalation clinical trial to test the candidate vaccine StreptInCor. The study will include four different doses (25 µg, 50 µg, 100 µg, and 200 µg) of StreptInCor produced under Good Manufacturing Practices (GMP) and formulated with aluminum hydroxide as the vaccine adjuvant. The adjuvant alone will be used as a placebo in this trial. Five groups, each consisting of twelve healthy adult volunteers, will randomly receive two doses of the vaccine or placebo with a 28-day interval, along with a booster dose six months after the initial vaccination
详细描述
This is a Phase I/IIa, randomized, double-blind, placebo-controlled, dose-escalation clinical trial to test the candidate vaccine StreptInCor. The study will include four different doses (25 µg, 50 µg, 100 µg, and 200 µg) of StreptInCor produced under Good Manufacturing Practices (GMP) and formulated with aluminum hydroxide as the vaccine adjuvant. The adjuvant alone will be used as a placebo in this trial.
Five groups, each comprising twelve healthy adult volunteers, will randomly receive two doses of the vaccine or placebo with a 28-day interval, along with a booster dose six months after the initial vaccination.
During the selection process, volunteers aged 18 to 45 years will undergo a general health assessment and serological tests to verify the absence of HIV and autoimmune diseases. Exclusion criteria include second-degree relatives or history of Rheumatic Fever (RF) or Rheumatic Heart Disease (RHD), as well as prior infections or recurrent diseases associated with S. pyogenes. All volunteers must sign an informed consent form before any procedures.
In the first phase of the trial, volunteers assigned to receive the lowest dose (25 µg) and three placebo volunteers will begin the vaccination scheme, maintaining blinding. One month after the second vaccination, all volunteers will be re-evaluated for safety, and the results will be submitted to the Data Safety Monitoring Committee (DSMC) for review. Only with a favorable opinion from the DSMC will the booster dose be administered to this group.
After the DSMC assesses the safety of these three doses, the second phase can commence. In this phase, volunteers assigned to the low-intermediate dose (50 µg) and three placebo volunteers will start vaccination, with safety evaluations occurring one month after the second dose. If the DSMC's opinion remains favorable, a booster at six months will be administered and re-evaluated by the DSMC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •• Healthy male or female volunteers, aged between 18 and 45 years;
- •Availability to undergo all procedures throughout the study period;
- •Provide free and informed consent to participate in the study.
排除标准
- •Participation in clinical trials within the last year
- •Participation in cohort studies
- •Diagnosis of concomitant infections or diseases that may affect immunity, including active HIV infection, hepatitis B, hepatitis C, diabetes mellitus, neoplasms, and autoimmune diseases;
- •Current or previous diagnosis or family history of ARF, chorea, obsessive-compulsive disorder, or glomerulonephritis;
- •Current or previous diagnosis of heart diseases;
- •Severe asthma or chronic obstructive pulmonary disease (COPD);
- •Abnormal neurological clinical assessment, especially chorea;
- •Use of treatments that may affect immunity in the last four weeks, including immunomodulators, corticosteroids (only systemic use for two weeks or more), or antineoplastic agents;
- •Use of treatments that may affect heart valves in the last four weeks or planned during the study period, including fenfluramine and dexfenfluramine;
- •Renal insufficiency determined by estimated creatinine clearance below 45 ml/min/1.73m²;
- •History of intolerance or allergy to any component of the study product, including antigen or adjuvant;
- •Presence of valve abnormalities or alterations in cardiac anatomy as defined by echocardiogram;
- •Altered electrocardiogram;
- •Evidence or suspicion of recent S. pyogenes infection based on clinical symptoms in the last four weeks;
- •Pregnancy, breastfeeding mother, or intention to become pregnant during the study period (only female participants);
- •Any other condition that may interfere with the study process as assessed by the researchers, including sample size and statistical power.
研究组 & 干预措施
Low dose Synthetic Vaccine Against Streptococcus Pyogenes- First arm
25 mcg / 50 mcg / 100 mcg / 200mcg of the experimental vaccine will be administered.
干预措施: Placebo (Other)
Aluminum hydroxide (a vaccine adjuvant) - fifth arm
Aluminum hydroxide (a vaccine adjuvant) will be administered as a placebo
干预措施: StrepIncor (Biological)
Aluminum hydroxide (a vaccine adjuvant) - fifth arm
Aluminum hydroxide (a vaccine adjuvant) will be administered as a placebo
干预措施: Placebo (Other)
结局指标
主要结局
Safety outcome
时间窗: From enrollment to the end of treatment at six months
• Safety outcome: The primary safety objective will be the absence of serious adverse events following immunization that have a reasonable causal relationship with the studied product in the StreptInCor and placebo groups;
Immunogenicity outcome
时间窗: From enrollment to the end of treatment at six months
Immunogenicity outcome: The primary immunogenicity outcome will be an increase of at least 4 times in IgG antibody levels against the StreptInCor peptide, 6 months after the last immunization.
次要结局
未报告次要终点
研究者
Roney Orismar Sampaio
MD, PhD
University of Sao Paulo General Hospital