Randomized, Double-blind, Phase 2 Clinical Trial Controlled With Conventional Bacillus Calmette-Guérin (BCG) Vaccine to Evaluate the Safety and Immunogenicity of a Recombinant BCG Vaccine That Expresses the Respiratory Syncytial Virus (RSV) Nucleoprotein (N) (rBCG-N-RSV) in Adults Over 60 Years of Age.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Occurrence, intensity, and duration of the local solicited AEs (evolution of the "flare-up") until the generation of the scar
研究概览
简要总结
This Phase 2 clinical study will evaluate the safety of the rBCG-N-RSV vaccine compared to conventional BCG in adults older than 60 years. It will also compare the cellular anti-mycobacterial immune response of both vaccines in adults older than 60 years and characterize the cellular immune response against RSV nucleoprotein (N) generated by the rBCG-N-RSV vaccine in adults older than 60 years as compared to the response induced by the conventional BCG.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Has completed the written informed consent process.
- •Males or females, over 60 years of age as of the date of signature of the informed consent form.
- •Has a stable state of health or controlled (health parameters within the normal range for their disease) chronic diseases that do not fall within the
排除标准
- •Willingness to comply with study procedures.
- •No plans to move to another city in the next 6 months and willing to be contacted by the research team within the study period.
- •Not participate in another research study in the previous 3 months, nor plans to participate in another research study in the next 6 months.
- •Agrees to avoid elective surgery during the study.
- •Willingness to receive HIV test results.
- •Not having received a BCG vaccination within the last 10 years before study vaccination.
- •Exlusion Criteria
- •Oral temperature ≥37.5°C, axillary ≥37.5°C or tympanic temperature ≥38.0°C in the last 24 hours.
- •Weight less than 50 kg, as well as BMI less than 18.5 or higher than 35 kg/m
- •History of treatment or current history of active or latent tuberculosis infection.
- •History of unprotected occupational exposure to an individual with active tuberculosis in a healthcare setting within the past 6 months.
- •Immunosuppressive drugs used within the previous 42 days (inhaled and topical corticosteroids are allowed).
- •Received documented investigational tuberculosis vaccine at any time.
- •Unstable hormonal status, i.e. subjects with any change (dose, formulation, or route) in hormone replacement therapies (including levothyroxine, insulin, estrogen, progesterone etc.) in the last 12 weeks.
- •History or laboratory evidence of any possible past, present, or future immunodeficiency status, including, but not limited to, any laboratory indication of HIV-1 infection.
- •Allergy to BCG vaccine or its components, as well as the existence of contraindications for BCG administration as described in the BCG prescribing information.
- •Previous medical history that may compromise the safety of the study participant, including but not limited to significant impairment of lung function (such as pulmonary diffusion of carbon dioxide <80% or FEV1 ≤80%) due to tuberculosis infection or other pulmonary disease; chronic heart disease with signs of heart failure (NYHA Class II Heart Failure or more) or coronary heart disease, suspicion of progressive neurological disease; uncontrolled epilepsy, liver disease.
- •Administration of attenuated vaccines within 30 days before the start of the study or 14 days for inactivated ones.
- •Having received transfusions or blood products within the 6 months before the start of the study.
- •Uncontrolled hypertension or systolic blood pressure greater than 160 mmHg at the beginning of the study or diastolic greater than 90 mmHg.
- •Active neoplasia.
- •Stage 2 or higher chronic obstructive pulmonary disease.
- •Chronic bronchial asthma with systemic corticosteroids, or with a history of having presented crises that have led to an emergency consultation within the last 2 months.
- •Renal disease with estimated or relative creatinine clearance ≤ 70 ml/min x 1.73 m
- •Evidence of a new acute illness that may compromise the safety of the study participant, such as fever (oral or axillary temperature greater than or equal to 37.5°C) or suspicion of active infection.
- •History or laboratory evidence of chronic viral hepatitis.
- •History of alcohol or drug abuse in the last 2 years.
- •Smoking more than 30 cigarettes a day, or cannabis use three or more days a week.
- •History of keloid formation.
- •Congenital diseases of importance, such that they weaken the basal condition of the volunteer.
- •Congenital or acquired absence of the spleen.
- •Coagulation disorders or known thrombocytopenia of less than 100,000 platelets/mm
- •Having undergone chemotherapy treatment in the last 6 months.
- •Generalized urticaria in the last 2 months.
- •History of hereditary or acquired angioneurotic edema.
- •Any previous medical condition that the investigator considers may compromise the safety of the subject in the study.
- •Not being available for all study visits (both face-to-face and by telephone) and specific instructions as appropriate (fasting, abstaining from intense physical exercise during the 24 hours before the study visits and during the 72 hours after vaccination).
- •Pregnant women or women of childbearing potential (WOCBP) who are unable or unwilling to utilize appropriate methods of contraception during the study.
- •Breast-feeding women.
- •Male with heterosexual sexual activity with WOCBP who do not agree to use adequate contraception.
研究组 & 干预措施
rBCG-N-RSV vaccine
rBCG-N-RSV is a live-attenuated vaccine of Mycobacterium bovis bacillus Calmette-Guerin (BCG) modified to heterologously and constitutively express the RSV nucleoprotein (N). The clinical formulation with this bacterium has been produced under strict quality and safety standards using current Good Manufacturing Practices (cGMP) in the United States of America (USA).
Pharmaceutical form: Lyophilisate for solution for injection
Medicinal product characteristics: Immunological
Route of administration: Intradermal use
Maximum duration of treatment: 1 Day
Maximum daily dose allowed: 0.1
Daily dose unit of measure: CFU/ml colony forming unit(s)/millilitre
Maximum total dose allowed: 0.1
Total dose unit of measure: CFU/ml colony forming unit(s)/millilitre
干预措施: Vaccination with rBCG-N-RSV (Biological)
Mycobacterium bovis bacillus Calmette-Guerin (BCG)
BCG is a cryo-lyophilized vaccine of an attenuated strain of Mycobacterium bovis BCG, used for active immunization against tuberculosis. It is currently administered in numerous countries worldwide according to national immunization plans.
Medicinal product characteristics: Immunological
Route of administration: Intradermal use
Maximum duration of treatment: 1 Day
Maximum daily dose allowed: 0.1
Daily dose unit of measure: CFU/ml colony forming unit(s)/millilitre
Maximum total dose allowed: 0.1
Total dose unit of measure: CFU/ml colony forming unit(s)/millilitre
干预措施: Vaccination with conventional BCG (BCG-WT) (Biological)
结局指标
主要结局
Occurrence, intensity, and duration of the local solicited AEs (evolution of the "flare-up") until the generation of the scar
时间窗: From vaccination through 180 days post-vaccination
Occurrence, intensity and duration of unsolicited AEs during the 6-month follow-up.
时间窗: From vaccination through 180 days post-vaccination
Occurrence of AEs during the 6-month follow-up duration.
时间窗: From vaccination through 180 days post-vaccination
Alterations to the hemogram and/or biochemical profile at 30- and 180- days post vaccination compared to pre-vaccination profile
时间窗: Day 30 and day 180 post-vaccination
Production of IFN-γ and IL-2 by T cells upon exposure to purified protein derivative (PPD) mycobacterial antigen via ELISPOT 7 days prior vaccination and 30- and 180-days post vaccination.
时间窗: Day 30 and day 180 post-vaccination
Production of IFN-γ and IL-2 by T cells upon exposure to recombinant RSV nucleoprotein antigen via ELISPOT 7 days prior vaccination and 30- and 180-days post vaccination
时间窗: Day 30 and day 180 post-vaccination
次要结局
- Presence and titers of serum IgG antibodies against Purified Protein Derived Mycobacterial antigen (PPD) via ELISA(Day 30 and day 180 post-vaccination)
- Presence and titers of serum IgG against RSV nucleoprotein via ELISA.(Day 30 and day 180 post-vaccination)