Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Evaluate Safety and Efficacy of H56:IC31 in Reducing the Rate of TB Disease Recurrence in HIV Negative Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 831
- 试验地点
- 6
- 主要终点
- Rate of TB Disease Recurrence (Relapse or Reinfection), Defined as TB Diagnosed by Confirmation of Mtb by Culture of Sputum.
研究概览
简要总结
This is a phase 2, double-blind, randomized (1:1), placebo-controlled trial with two parallel groups.
- H56:IC31 (investigational vaccine)
- Placebo
900 HIV-negative adults with a diagnosis of drug susceptible pulmonary TB are planned to be included, recruited from TB clinics with established relationships to the trial sites at the start of their TB treatment.
5 study sites in South Africa: 2 sites from the AURUM institute (Klerksdorp and Tembisa) and 3 in Cape Town at TASK Applied Science (TASK), the University of Cape Town Lung Institute (UCTLI) and South African Tuberculosis Vaccine Initiative (SATVI) under UCT, respectively.
1 study site in Tanzania (TZ): 1 site at Mbeya Medical Research Centre (MMRC) under the National Institute for Medical Research (NIMR).
详细描述
This is a phase 2, double-blind, randomized (1:1), placebo-controlled trial with two parallel groups.
- H56:IC31 (investigational vaccine)
- Placebo
900 HIV-negative adults with a diagnosis of drug susceptible pulmonary TB are planned to be included, recruited from TB clinics with established relationships to the trial sites at the start of their TB treatment.
5 study sites in South Africa: 2 sites from the AURUM institute (Klerksdorp and Tembisa) and 3 in Cape Town at TASK Applied Science (TASK), the University of Cape Town Lung Institute (UCTLI)) and South African Tuberculosis Vaccine Initiative (SATVI) under UCT, respectively.
1 study site in Tanzania (TZ): 1 site at Mbeya Medical Research Centre (MMRC) under the National Institute for Medical Research (NIMR).
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)
盲法说明
The unblinded persons in the study are the study vaccine manager (and designee) who manages the participant inventory log(s) at the trial site, the unblinded site staff, and the unblinded clinical trial site monitor(s) responsible for monitoring the investigational product at the trial site. All unblinded persons must take care to not reveal individual participant treatment assignments to any blinded member of the study team. There is an unblinded contact person at the sponsor's site in order to manage queries from the unblinded site staff or the unblinded monitors in the trial.
The study vaccine manager (and designee) should be a designated site team member, such as the study pharmacist. Unblinded site staff must not participate in the evaluation of adverse events.
The randomization list will be provided by the unblinded statistician and will be implemented as a module in the eCRF.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Completed the written informed consent process.
- •Agrees to give access to medical records for trial related purposes.
- •Was HIV-negative (self-reported) with a diagnosis of drug susceptible pulmonary TB at the start of the TB treatment.
- •Able to provide 2 separate sputum samples within ≤ 7 days of starting TB treatment. Participants are not expected to provide sputum samples prior to starting TB treatment if their 1st screening visit (V1) is performed on the same day as their 2nd screening visit (V2).
- •Confirmed Mtb negative by smear AFB microscopy of 2 separate sputum samples taken at V
- •Participants unable to produce sputum, but considered asymptomatic by the investigator, may be considered Mtb negative and eligible for inclusion.
- •Confirmed HIV negative at V
- •Completed ≥ 5 months (22 weeks) of TB treatment with treatment still ongoing at the time of the 1st vaccination and total treatment time not extended beyond 28 weeks.
- •Aged ≥ 18 years on the date of V1 and ≤ 60 years on the date of V3= Day
- •Agrees to stay in contact with the clinical trial site for the duration of the trial, provide updated contact information as necessary, and has no current plans to move from the area for the duration of the trial.
排除标准
- •Diagnosis or co-diagnosis of extra pulmonary TB.
- •Hospitalized for the current episode of drug susceptible pulmonary TB disease.
- •History of or ongoing severe disease that in the opinion of the investigator might affect the safety of the participant or the immunogenicity of the investigational product.
- •Insulin dependent diabetes.
- •History of allergic disease or reactions likely to be exacerbated by any component of the investigational product.
- •History or laboratory evidence of immunodeficiency, autoimmune disease or immunosuppression.
- •History of chronic hepatitis.
- •Severe anemia, defined as hemoglobin less than 10 g/dL or a hematocrit less than 30% based on most recent hematology obtained before randomization.
- •History of receipt of treatment against active TB, prior to the current treatment episode, within the last 5 years
- •Receipt of any investigational TB vaccine previously.
- •Receipt or planned receipt of any investigational drug or investigational vaccine from V1 through V8= Day
- •Receipt or planned receipt of any licensed vaccine from V1 through V6= Day 70, except for SARS-Cov-2 vaccines recommended by national vaccination programs which will be allowed if given > 28 days before and from the time of administration of clinical trial product.
- •Receipt of treatment likely to modify the immune response (e.g. blood products, immunoglobulins, immunosuppressive treatment) within 42 days before V3= Day 0 through V6= Day
- •Inhaled and topical corticosteroids are permitted.
- •Has a body mass index (BMI) < 13 (weight, kg / height, m2) on the date of V
- •Female participants of childbearing potential (not sterilized, menstruating or within 1 year of last menses, if post-menopausal): if not willing to use an acceptable method to avoid pregnancy (sterile sexual partner, sexual abstinence, hormonal contraceptives (oral, injection, transdermal patch, or implant) or intrauterine device from 28 days before V3= Day 0 until 2 months after the 2nd vaccination.
- •Female participants: if lactating / nursing, or pregnant as per positive pregnancy test on V
- •Not suitable for inclusion in the opinion of the investigator.
研究组 & 干预措施
H56:IC31
The H56 fusion protein is formulated with IC31 in a GMP-compliant environment in a ready to use final formulated vaccine.
H56:IC31 is administered twice with a 56 days (+/-10) interval, as 5 μg H56 adjuvanted with IC31 consisting of 500 nmol KLK and 20 nmol ODN1a, in a total volume of 0.5mL by the intramuscular route in the deltoid area using standard aseptic technique.
干预措施: H56:IC31 (Biological)
Placebo
Sterile saline for injection
干预措施: Placebo (Biological)
结局指标
主要结局
Rate of TB Disease Recurrence (Relapse or Reinfection), Defined as TB Diagnosed by Confirmation of Mtb by Culture of Sputum.
时间窗: During the period starting 14 days after the 2nd vaccination (V6= Day 70) and ending 12 months after the 2nd vaccination
To evaluate the following in HIV-negative participants who have completed at least 5 months (22 weeks) treatment for drug-susceptible pulmonary TB and who test negative for acid fast bacilli (AFB) on sputum smear microscopy prior to vaccination (participants unable to produce sputum, and considered asymptomatic by the investigator, may be considered Mtb negative): Efficacy of H56:IC31 compared to placebo in reducing the rate of recurrent TB disease (relapse or reinfection).
次要结局
- Number of Participants With Adverse Events Occurring During the First 14 Days After Each of the 1st and 2nd Vaccinations by System Organ Class and Preferred Term(Day 0 through Day 70)
- Summary of the Number of Participants Reporting All Adverse Events Within the 14 Days After Each of the 1st and 2nd Vaccinations(Day 0 through Day 70)
- Number of Participants With Serious Adverse Events Including Medically Important Events Occurring After the 1st Vaccination Through the End of the Trial(Day 0 through Day 421)
- Efficacy of H56:IC31 Compared to Placebo in Reducing the Rate of TB Disease Relapse(Day 70 through Day 421)
- Efficacy of H56:IC31 Compared to Placebo in Reducing the Rate of TB Disease Reinfection(Day 70 through Day 421)
- Antigen-specific Cell-mediated Immune Responses to H56:IC31 by Whole Blood (Absolute Values)(Day 0 through Day 70)
- Humoral Immune Responses to H56:IC31 by Immunoglobulin G ELISA (Absolute Values)(Day 0 through Day 70)
- Antigen-specific Cell-mediated Immune Responses to H56:IC31 by Whole Blood (Fold Increase)(Day 0 through Day 70)
- Humoral Immune Responses to H56:IC31 by Immunoglobulin G ELISA (Fold Increase From Baseline to Visit 6 [Day 70])(Day 0 through Day 70)