Singh Manjula, Mehendale Sanjay, Guleria Randeep, Sarin Rohit, Tripathy Srikanth, Gangakhedkar Raman R, Katoch Kiran, Pandey Ravindra Mohan, Panda Samiran, Pati Sanghamitra, Mohapatra Prasanta Raghab, Joshi Sindhu, Narasimhaiah Somashekar, Kodan Parul, Bhaskar Sangeeta, Rani Rajni, Khan Abdul Mabood, Swaminathan Soumya
ECD, Indian Council of Medical Research, New Delhi, India
Clinical Research, Hinduja Hospital, Mumbai, Maharashtra, India.
BMJ Open. 2024 Aug 31;14(8):e082916. doi: 10.1136/bmjopen-2023-082916.
Tuberculosis (TB) continues to be one of the deadliest infectious diseases over the centuries, killing more people worldwide than any other single infectious disease. There is an urgent need for additional strategies which can expedite efforts to combat TB including a preventive vaccine. In this endeavour, we have developed a protocol for a multisite, double-blind, placebo-controlled clinical trial in India that aims to evaluate the efficacy and safety of two TB vaccines; namely, VPM1002 and Immuvac () () (MIP) among healthy household contacts (HHCs) of sputum smear-positive pulmonary TB (PTB) patients.
In the three-arm randomised double-blind placebo-controlled trial study protocol, a total of 12 000 HHCs (aged 6-99 years) of sputum smear-positive PTB patients will be randomised to receive either of the two vaccine candidates VPM1002 and MIP or placebo. The primary efficacy endpoint is the prevention of microbiologically confirmed TB. Secondary endpoints will include (1) prevention against Latent TB infection, (2) incidence of adverse events and serious adverse events in study participants, (3) efficacy of vaccine in prevention of PTB/extra PTB in different age groups (6-18 years, 19-35 years, 36-60 years and above 60 years) and (4) immunogenicity of VPM1002 and MIP at month 2 and month 6 after first vaccination in terms of flow cytometric analysis of specific CD4+ and CD8+ T cells secreting cytokines and Luminex assays for the presence of different cytokines in the sera and supernatants of peripheral blood mononuclear cells cultures stimulated with whole cell lysates of and subsequently similar analysis for the cases who develop TB postvaccination during the follow-up period.
Ethics committees' approvals have been granted by the Institutional Human Ethics Committees of all participating centres in this study and the names of the ethics committees and approvals are as follows: (1) National Institute for Research in Tuberculosis (NIRT)-Chennai (including subsites): ECR/135/Inst/TN/2013/RR-19, Approval No. 390/NIRT-Institutional Ethics Committee (IEC)/2018 dated 5 December 2018 (NIRT-Madurai-ECR/1365/Inst/TN/2020; approval dated 8 June 2020; NIRT, Vellore: ECR/1215/Inst/TN/2019; approval dated 26 September 2020); (2) All India Institute of Medical Sciences (AIIMS), Delhi (including subsites)-Institute Ethics Committee, ECR/547/Inst/DL/2014/RR-17 ECR/538/Inst/DL/2014/RR-20; approval No.IEC-385/06-07-2018, approval OP-28/05.04.2019 and SFH- ECR/593/Inst/DL/2014/RR-20 IEC/VMMC/SJH/project/2019-05/25 ; 23 May 2019; (3) National Institute of Tuberculosis and Respiratory Diseases (NITRD), Delhi: ECR/315/Inst/DL/2013/RR-19; approval IEC-No-NITRD/EC/2019/9004; 8 January 2019; (4) Pune-National AIDS Research Institute (NARI) and subsite-ECR/23/Inst/MH/2013/RR-19; IEC-NARI/EC/approval/2018/196; 29 May 2018; (5) Regional Medical Research Centre-Bhubaneshwar-ECR/911/Inst/OR-2017/RR-21; approval, dated 25 April 2018; Subsites- AIIMS, Bhubaneshwar ECR/534/Inst/OD/2014/RR-17 and 20 approval No. T/EMF/Pulm. Med/19/01 dated 13 May 2019; SCB, Cuttack No. No.ECR/84/Inst/OR/2013/RR-20; approval no.186 dated 7 February 2020; (6) NTI-Bengaluru: Ethics Committee-No-ECR/1819/Inst/KA/2019; approval No NTI-IEC/1.2019/principal investigator, dated 31 January 2019; (7) BMMRC, Hyderabad- ECR/450/Inst/AP/2013/RR-16 approval No. 779/BMMRC/2018/IEC, dated 11 June 2018 (Subsite Share India- Mediciti Ethics Committee-ECR/283/Inst/AP/2013/RR-20; Approval no. EC/11/VII/2K20(1) dated 11 July 2020) and (8) SJMC-Bengaluru: ECR/238/Inst/KA/2013/RR-19; approval IEC/1/491/2020; 7 August 2020.The trial findings will be published in accordance with the Consolidated Standards of Reporting Trials guidance. The results of this clinical trial will be presented at scientific conferences and disseminated through publications in peer-reviewed journals, conference presentations and shared with Ministry of Health and Family Welfare, policy-makers and other stakeholders.
CTRI/2019/01/017026.
几个世纪以来，结核病一直是最致命的传染病之一，在全球造成的死亡人数超过任何其他单一传染病。迫切需要更多策略来加快抗击结核病的努力，包括预防性疫苗。在此过程中，我们制定了一项在印度进行的多中心、双盲、安慰剂对照临床试验方案，旨在评估两种结核病疫苗，即VPM1002和Immuvac（）（）（MIP）在痰涂片阳性肺结核（PTB）患者的健康家庭接触者（HHC）中的疗效和安全性。
在这项三臂随机双盲安慰剂对照试验研究方案中，总共12000名痰涂片阳性PTB患者的HHC（年龄6 - 99岁）将被随机分配接受两种候选疫苗VPM1002和MIP中的一种或安慰剂。主要疗效终点是预防微生物学确诊的结核病。次要终点将包括：（1）预防潜伏性结核感染；（2）研究参与者中不良事件和严重不良事件的发生率；（3）疫苗在不同年龄组（6 - 18岁、19 - 35岁、36 - 60岁及60岁以上）预防PTB/肺外PTB的疗效；（4）首次接种后第2个月和第6个月时，通过对分泌细胞因子的特定CD4 +和CD8 + T细胞进行流式细胞术分析以及对用 全细胞裂解物刺激的外周血单个核细胞培养物的血清和上清液中不同细胞因子的存在进行Luminex检测，评估VPM1002和MIP的免疫原性，随后对随访期间接种疫苗后发生结核病的病例进行类似分析。
本研究所有参与中心的机构人类伦理委员会均已批准伦理委员会的申请，伦理委员会的名称及批准情况如下：（1）金奈国家结核病研究所（NIRT）（包括分站）：ECR/135/Inst/TN/2013/RR - 19，批准号390/NIRT - 机构伦理委员会（IEC）/2018，日期为2018年12月5日（NIRT - 马杜赖 - ECR/1365/Inst/TN/2020；批准日期为2020年6月8日；NIRT，韦洛尔：ECR/1215/Inst/TN/2019；批准日期为2020年9月26日）；（2）德里全印度医学科学研究所（AIIMS）（包括分站） - 机构伦理委员会，ECR/547/Inst/DL/2014/RR - 17，ECR/538/Inst/DL/2014/RR - 20；批准号IEC - 385/06 - 07 - 2018，批准OP - 28/05.04.2019和SFH - ECR/593/Inst/DL/2014/RR - 20，IEC/VMMC/SJH/project/2019 - 05/25；2019年5月23日；（3）德里国家结核病和呼吸系统疾病研究所（NITRD）：ECR/315/Inst/DL/2013/RR - 19；批准号IEC - No - NITRD/EC/2019/9004；2019年1月8日；（4）浦那 - 国家艾滋病研究所以及分站 - ECR/23/Inst/MH/2013/RR - 19；IEC - NARI/EC/批准/2018/196；2018年5月29日；（5）布巴内什瓦尔区域医学研究中心 - ECR/911/Inst/OR - 2017/RR - 21；批准日期为2018年4月25日；分站 - AIIMS，布巴内什瓦尔ECR/534/Inst/OD/2014/RR - 17以及20批准号T/EMF/Pulm.Med/19/01，日期为2019年5月13日；SCB，科塔克编号No.ECR/84/Inst/OR/2013/RR - 20；批准号186，日期为2020年2月7日；（6）班加罗尔NTI：伦理委员会 - No - ECR/1819/Inst/KA/2019；批准号NTI - IEC/1.2019/首席研究员，日期为2019年1月31日；（7）海得拉巴BMMRC - ECR/450/Inst/AP/2013/RR - 16，批准号779/BMMRC/2018/IEC，日期为2018年6月11日（分站Share India - Mediciti伦理委员会 - ECR/283/Inst/AP/2013/RR - 20；批准号EC/11/VII/2K20(1)，日期为2020年7月11日）以及（8）班加罗尔SJMC：ECR/238/Inst/KA/2013/RR - 19；批准号IEC/1/491/2020；2020年8月7日。试验结果将按照《报告试验的统一标准》指南发表。本临床试验的结果将在科学会议上展示，并通过在同行评审期刊上发表、会议报告以及与卫生和家庭福利部、政策制定者及其他利益相关者分享等方式进行传播。
CTRI/2019/01/017026
