NCT02337270已完成1 期
Phase 1, Open-label Clinical Trial to Evaluate the Safety and Immunogenicity of an Adenovirus-based Tuberculosis Vaccine Administered by Aerosol
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Number of participants reporting adverse events
研究概览
简要总结
This is a phase 1 study, in healthy volunteers who have previously been immunized with bacilli Calmette Guerin (BCG), to evaluate the safety and immune responses that develop in the blood and lungs following the administration by aerosol of a new experimental adenovirus-based vaccine for tuberculosis (TB), Ad5Ag85A.
详细描述
This is a phase 1, open label study to evaluate the safety and immunogenicity of a single administration of one of two doses of a recombinant replication deficient human adenoviral (Ad5) TB vaccine containing the immunodominant antigen Ag85A delivered to the respiratory tract by aerosol in healthy volunteers with a history of BCG immunization.
28 healthy volunteers will be enrolled. The first cohort (n=8) will receive a lower dose of vaccine using the AeroNeb Solo Vibrating Mesh Nebulizer. For the second cohort (n=20) participants will be randomized to either a higher dose of vaccine by aerosol (n=10) or intramuscular administration (n=10). Cellular immune responses in the lung and peripheral blood will be evaluated
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
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy human subjects who are between 18 and 55 years of age with a history of BCG vaccination.
- •HIV antibody negative
- •Able to understand and comply with protocol requirements and instructions; able to attend scheduled study visits and complete required investigations.
- •For women, negative pregnancy test and practicing two acceptable forms of contraception for the duration of the study (barrier contraceptive, birth control pill, surgically sterile, post-menopausal 2 years, abstinence)
- •For men, using barrier contraception for the duration of the study
排除标准
- •Pregnant or lactating women
- •Subjects who have any acute or chronic illnesses including active tuberculosis, any relevant findings on physical examination or are receiving any drug treatment in the opinion of the investigator likely to affect the immune system including current use of inhaled or nasal steroids.
- •Subjects with a history of any bleeding disorder or receiving any drug treatment that in the opinion of the investigator may increase the risk of bleeding
- •Subjects with a history of respiratory disease, e.g. asthma, chronic bronchitis, chronic obstructive pulmonary disease (COPD).
- •Current smokers, including e-cigarettes, and ex-smokers who have quit within the last year, as reported by the subject
- •Subjects with clinically significant abnormality of baseline spirometry tests
- •Any health-related condition for which study bronchoscopy is contraindicated
- •Subjects who have a history of active or latent TB infection or whose PBMC's are responsive to ESAT6/CFP10 stimulation using a commercial interferon gamma release assay for TB [consistent with latent TB infection].
- •Subjects whose baseline laboratory values are outside of the normal range unless the abnormality is considered not to be of clinical relevance by the Investigator. A single repeat test is allowed during the screening period.
- •Subjects whose use of alcohol or drugs would, in the opinion of the investigator, interfere with adherence to the study protocol.
- •Subjects who are using, or have a history of using, inhaled cocaine, metamphetamine or other inhaled or smoked recreational drugs. Subjects who give a history of last smoking marijuana more than a year ago may be enrolled, as long as they do not smoke marijuana for the duration of the study.
- •Failure to provide written consent.
- •Known allergy to vaccine components
- •Previous vaccination with Ad5Ag85A or any other experimental TB vaccine
- •Known exposure to active TB within past 6 months or subjects whose occupation puts them at increased risk of TB exposure (based on Hamilton Health Science/St Joseph Healthcare list of high risk personnel)
- •Any abnormality on chest x-ray suggestive of active or remote tuberculosis infection or evidence on chest-x-ray of clinically significant respiratory disease.
- •PPD skin test within last 12 months
结局指标
主要结局
Number of participants reporting adverse events
时间窗: Over 24 weeks
Adverse events will be assessed according to the CTCAE Expanded Common Toxicity Criteria at 48-72 hours after vaccination, and at weeks 2, 4, 8, 12, 16 and 24
次要结局
- Immune responses measured from induced sputum compared with bronchoalveolar lavage(Two weeks after vaccination)
- Number of participants developing a positive interferon release assay for TB after vaccination with Ad5Ag85A(At 16 weeks)
- Immune response to vaccination correlated with pre-existing anti-adenoviral antibodies(Eight weeks after vaccination)
- immune responses measured from induced sputum compared with bronchoalveolar lavage(Eight weeks after vaccination)
- Immune response to vaccine correlated with dose of vaccine received by inhalation(Eight or 12 weeks after vaccination)
- Immunogenicity of inhaled administration of Ad5Ag85A compared with intramuscular administration(Twelve weeks after vaccination)
- Immunogenicity of one of two doses of Ad5Ag85A administered by aerosol(Eight (first cohort) or twelve (second cohort) weeks after vaccination)
- Number of participants reporting adverse effects correlated with dose of vaccine received by inhalation(Over 24 weeks)
- Number of participants reporting adverse events with inhaled administration of Ad5Ag85A compared with intramuscular administration(Over 24 weeks)
- Number of participants reporting adverse events correlated with level of pre-existing anti-adenoviral antibodies(Over 24 weeks)
研究者
研究点 (2)
Loading locations...
相似试验
终止
1 期
Safety & Immunogenicity of RVM-V001/RVM-V002 or RVMV001+RVMV002 (Co Administered as Separate Injections) in Healthy IndividualsInfectious DiseaseCOVID-19NCT05788185RVAC Medicines (US), Inc.24
已完成
1 期
A Study to Determine the Safety and Immunogenicity of Co-administration of the Candidate Influenza Vaccine MVA-NP+M1 and Seasonal Influenza VaccineInfluenzaNCT01465035University of Oxford24
终止
1 期
Safety and Immunogenicity of Co-administration of Candidate Influenza Vaccine MVA-NP+M1 and Viroflu® Seasonal Influenza VaccineInfluenzaNCT02014168University of Oxford3
已完成
1 期
Effect of Adjuvant & Route of Administration on Safety & Immunogenicity of NDV-3 VaccineStaphylococcal InfectionsYeast InfectionsCandidiasisNCT01447407NovaDigm Therapeutics, Inc.164
已完成
1 期
Study to Assess dHER2+AS15 Cancer Vaccine Given in Combination With Lapatinib to Patients With Metastatic Breast CancerMetastatic Breast CancerNCT00952692Michael Morse, MD12