A large Phase 3 trial will evaluate whether the M72/AS01E vaccine candidate can protect adolescents and adults from pulmonary tuberculosis

一项大型的3期试验将评估M72/AS01E候选疫苗是否可以保护青少年和成年人免受肺结核的影响

Clinical trial site at University of the Witwatersrand, Johannesburg, South Africa, is first of up to 60 sites in seven countries

南非约翰内斯堡威特沃特斯兰德大学（University of Witwatersrand）的临床试验场地是七个国家多达60个场地中的第一个

The M72/AS01E vaccine candidate could be the first new TB vaccine in 100 years if proven effective

如果证明有效，M72/AS01E候选疫苗可能是100年来第一种新的结核病疫苗

CAMBRIDGE, Mass., March 19, 2024 /PRNewswire/ -- The Bill & Melinda Gates Medical Research Institute (Gates MRI) today announced that a Phase 3 clinical trial to assess the efficacy of the M72/AS01E tuberculosis (TB) vaccine candidate is now underway, with first doses given in South Africa, where TB takes a heavy toll.

马萨诸塞州剑桥市，2024年3月19日/PRNewswire/--比尔和梅琳达·盖茨医学研究所（Gates MRI）今天宣布，一项评估M72/AS01E结核病（TB）候选疫苗疗效的3期临床试验正在进行中，第一剂是在南非进行的，在南非，结核病造成了沉重的损失。

If shown to be well-tolerated and effective, M72/AS01E could potentially become the first vaccine to help prevent pulmonary TB in adolescents and adults, the most common form of the disease, and the first new TB vaccine in over a century.   .

如果证明M72/AS01E具有良好的耐受性和有效性，则可能成为第一种有助于预防青少年和成人肺结核的疫苗，这是该疾病最常见的形式，也是一个多世纪以来第一种新的结核病疫苗。。

Globally, according to the World Health Organization, an estimated 10.6 million people fell ill with TB in 2022 and 1.3 million died — over 3,500 people per day. The disease primarily affects people in low- and middle-income countries, and those at highest risk are often living in poverty, with poor living and working conditions and undernutrition.

根据世界卫生组织的数据，2022年全球估计有1060万人患有结核病，130万人死亡，每天超过3500人。该疾病主要影响中低收入国家的人，风险最高的人往往生活在贫困之中，生活和工作条件差，营养不良。

In South Africa alone, around 280,000 people are diagnosed with TB each year. .

仅在南非，每年就有大约280000人被诊断出患有结核病。。

'The launch of this pivotal Phase 3 trial demonstrates our commitment to harnessing the power of medical innovation to fight diseases like TB that are particularly devastating for low- and middle-income countries,' said Emilio A. Emini, Ph.D., CEO of the Gates MRI. 'Clinical study of the vaccine will still require years, but our incredible partners in South Africa and elsewhere who have come together for the Phase 3 study share our hope in the vaccine's potential.'.

盖茨MRI首席执行官埃米利奥·埃米尼（EmilioA.Emini）博士说：“这项关键的第三阶段试验的启动表明，我们致力于利用医学创新的力量来对抗结核病等疾病，这些疾病对中低收入国家来说尤其具有毁灭性。疫苗的临床研究仍需要数年时间，但是，我们在南非和其他地方的令人难以置信的合作伙伴聚集在一起进行第三阶段研究，他们对疫苗的潜力抱有共同的希望。”。

The Gates MRI, a nonprofit organization and subsidiary of the Bill & Melinda Gates Foundation, is sponsoring the trial, which is supported by funding from the Gates Foundation and Wellcome. The M72/AS01E vaccine candidate has been in development since the early 2000s. It was originally designed and clinically evaluated by the biopharma company GSK up to the proof-of-concept phase (Phase 2b), in partnership with Aeras and the International AIDS Vaccine Initiative (IAVI) and was funded by GSK and in part by the Gates Foundation.

盖茨MRI是比尔和梅琳达·盖茨基金会（Bill＆MelindaGates Foundation）的一个非营利组织和子公司，正在赞助这项试验，该试验得到了盖茨基金会（Gates Foundation）和惠康（Wellcome）的资助。M72/AS01E候选疫苗自2000年代初以来一直在开发中。它最初由生物制药公司GSK与Aeras和国际艾滋病疫苗倡议（IAVI）合作设计和临床评估，直至概念验证阶段（2b阶段），并由GSK资助，部分由盖茨基金会资助。

In 2020, GSK announced a partnership with the Gates MRI for further development of M72/AS01E. GSK continues to provide technical assistance to the Gates MRI, supplies the adjuvant component of the vaccine for the Phase 3 trial and will provide the adjuvant post licensure should the trial be successful.

2020年，葛兰素史克宣布与盖茨MRI合作，进一步开发M72/AS01E。葛兰素史克继续为盖茨MRI提供技术援助，为3期试验提供疫苗的佐剂成分，如果试验成功，将提供佐剂后许可。

An adjuvant is an ingredient used in some vaccines that can help create a stronger immune response. .

佐剂是一些疫苗中使用的一种成分，可以帮助产生更强的免疫反应。。

Making vaccines accessible and affordable for communities in areas of high disease burden in the long-term is a priority for all trial partners. The Gates MRI has worked with a wide range of stakeholders, including communities around clinical trial sites, to guide the TB candidate vaccine to Phase 3.

所有试验合作伙伴的优先事项是，从长远来看，使高疾病负担地区的社区能够获得和负担得起疫苗。盖茨MRI与包括临床试验地点周围社区在内的广泛利益相关者合作，指导结核病候选疫苗进入第三阶段。

To this end, the Gates MRI, GSK, Wellcome and the Gates Foundation are working together to understand the potential demand for the vaccine and build an end-to-end plan to ensure long-term sustainable access, should the trial be successful; from supporting research and building an evidence-base for the potential impact of the vaccine and community requirements for uptake, to collaborating with multilateral, regional and country partners required to introduce the vaccine.

为此，如果试验成功，盖茨MRI，葛兰素史克，惠康和盖茨基金会正在共同努力，以了解对疫苗的潜在需求，并制定端到端计划，以确保长期可持续获取；从支持研究和为疫苗的潜在影响和社区对接种的要求建立证据基础，到与引入疫苗所需的多边、区域和国家合作伙伴合作。

Additionally, the trial funders are planning to establish an international advisory group comprised of representatives from all these groups to provide input on the overall program..

此外，试验资助者正计划成立一个由所有这些团体的代表组成的国际咨询小组，为整个项目提供投入。。

Developing and ensuring access to global health products is a complex task. As such, global collaboration and strong partnerships are a core component of planning for future access to the candidate vaccine.

开发和确保获得全球保健产品是一项复杂的任务。因此，全球合作和强大的伙伴关系是规划未来获得候选疫苗的核心组成部分。

'Reaching Phase 3 with an urgently needed TB vaccine candidate is an important moment for South Africans because it demonstrates that there is a strong local and global commitment to fight a disease that remains distressingly common in our communities,' said Dr. Lee Fairlie, Director of Maternal and Child Health at Wits RHI at University of the Witwatersrand, Johannesburg, South Africa, and national principal investigator for the trial in South Africa.

南非约翰内斯堡威特沃特斯兰德大学（University of the Witwatersrand）Wits RHI妇幼保健主任李·费尔利（Lee Fairlie）博士说：“对于南非人来说，使用急需的结核病疫苗候选人进入第三阶段是一个重要的时刻，因为这表明当地和全球都有强烈的承诺，要与一种在我们社区仍然普遍存在的疾病作斗争。”，以及南非试验的国家首席研究员。

'South Africa also has considerable experience with TB- and vaccine-related clinical trials and a strong track record for protecting patient safety and generating high quality data essential for regulatory approvals.'.

“南非在结核病和疫苗相关的临床试验方面也有丰富的经验，在保护患者安全和产生监管批准所必需的高质量数据方面有着良好的记录。”。

At full capacity, the trial will include up to 20,000 participants, including people living with HIV, at up to 60 trial sites in seven countries — South Africa, Zambia, Malawi, Mozambique, Kenya, Indonesia and Vietnam. Participants will receive either the investigational M72/AS01E vaccine or a placebo in what is known as a double-blind trial, meaning neither the trial participant nor the clinical investigators will know who receives vaccine or placebo.

该试验将在南非、赞比亚、马拉维、莫桑比克、肯尼亚、印度尼西亚和越南七个国家的多达60个试验地点全面展开，包括艾滋病毒感染者在内的多达20000名参与者。参与者将在所谓的双盲试验中接受研究性M72/AS01E疫苗或安慰剂，这意味着试验参与者和临床研究人员都不知道谁会接受疫苗或安慰剂。

This approach is considered the gold standard for evaluating the safety and efficacy of an investigational vaccine.  .

这种方法被认为是评估研究疫苗安全性和有效性的金标准。。

'After dedicating over 20 years to developing this essential candidate vaccine, we at GSK are delighted that the Phase 3 trial is underway. Developing and ensuring access to global health products is complex but our collaboration with the Gates MRI, Wellcome and the Gates Foundation exemplifies the transformative power of leveraging diverse partners' expertise to change the trajectory of challenging diseases, like TB, which place a huge burden on communities around the world,' said Deborah Waterhouse, CEO, ViiV Healthcare and President, Global Health, GSK. .

“在花了20多年的时间开发这种重要的候选疫苗后，我们GSK很高兴3期试验正在进行中。首席执行官黛博拉·沃特豪斯（DeborahWaterhouse）说，开发和确保获得全球保健产品是一项复杂的工作，但我们与盖茨MRI、惠康（Wellcome）和盖茨基金会（Gates Foundation）的合作证明了利用不同合作伙伴的专业知识来改变结核病等挑战性疾病的发展轨迹的变革力量，ViiV Healthcare和GSK全球健康总裁。。

While TB is one of the world's deadliest infectious diseases — and the leading cause of death amongst people living with HIV — the only available TB vaccine, BCG, dates back to 1921. It protects babies and young children against severe forms of TB, but it offers inadequate protection for adolescents and adults against the pulmonary form of the disease, which is primarily responsible for transmission of the TB bacterium..

虽然结核病是世界上最致命的传染病之一，也是艾滋病毒感染者死亡的主要原因，但唯一可用的结核病疫苗卡介苗可以追溯到1921年。它可以保护婴儿和幼儿免受严重形式的结核病的侵害，但对青少年和成年人的肺部疾病保护不足，而肺部疾病是结核病传播的主要原因。。

'If effective, M72/AS01E could reinvigorate a global fight against TB that has been weakened by the COVID-19 pandemic,' said Alemnew Dagnew, M.D., who leads development of M72/AS01E at the Gates MRI. 'I am particularly excited to see this trial get underway because when I was working as a physician in Ethiopia, I saw first-hand what pulmonary TB does to communities — and a vaccine that could help prevent that from happening would be transformative.'.

盖茨MRI研发M72/AS01E的负责人Alemnew Dagnew医学博士说：“如果有效，M72/AS01E可能会重振全球抗击因新型冠状病毒大流行而减弱的结核病的斗争。我特别兴奋地看到这项试验正在进行，因为当我在埃塞俄比亚担任医生时，我亲眼目睹了肺结核对社区的影响，而一种有助于预防这种情况发生的疫苗将具有变革性。”。

Dagnew noted that TB is both a health problem and a socioeconomic problem. He said the disease primarily affects people during their prime working years, leaving families without income and children without parents. Almost half of TB-affected households face costs higher than 20% of their household income..

达格纽指出，结核病既是一个健康问题，也是一个社会经济问题。他说，这种疾病主要影响工作旺季的人，使家庭没有收入，孩子没有父母。几乎一半受结核病影响的家庭面临的成本高于其家庭收入的20%。。

'We must continue to move with urgency to develop and equitably deliver innovative tools with the potential to transform the prevention, diagnosis, and treatment of TB. The start of the Gates MRI's M72 TB vaccine candidate Phase 3 clinical trial marks a pivotal moment in the fight to end TB, which devastatingly afflicts the world's most vulnerable communities.

“我们必须继续紧迫地开发和公平地提供创新工具，这些工具有可能改变结核病的预防，诊断和治疗。盖茨MRI的M72结核病候选疫苗3期临床试验的开始标志着结束结核病斗争的关键时刻，结核病严重影响着世界上最脆弱的社区。

We think this trial marks the beginning of a series of opportunities that will usher in the most promising pipeline ever of new TB tools. The Gates Foundation remains committed to supporting local and global partners to accelerate the solutions needed to save lives and reduce suffering from this preventable disease,' said Trevor Mundel, President, Global Health, Bill & Melinda Gates Foundation..

我们认为，这项试验标志着一系列机会的开始，这些机会将迎来有史以来最有希望的新结核病工具管道。盖茨基金会全球健康总裁特雷弗·蒙德尔（TrevorMundel）说，盖茨基金会仍然致力于支持当地和全球合作伙伴，以加快挽救生命和减少这种可预防疾病的痛苦所需的解决方案。。

Alex Pym, Director of Infectious Disease at Wellcome, said: 'While it is a long journey to results, the start of this trial in South Africa brings us a critical step closer to having an effective vaccine to protect those most at risk of TB. Global collaboration with regulators, in-country decision makers and communities affected is crucial if those who need it most are to benefit from this vaccine, should the trial be successful.' .

惠康（Wellcome）传染病主管亚历克斯·皮姆（AlexPym）说：“虽然要取得结果还有很长的路要走，但在南非开始的这项试验使我们离获得有效疫苗以保护结核病高危人群的目标又近了一步。如果试验成功，如果最需要疫苗的人要从这种疫苗中受益，那么与监管机构、国内决策者和受影响社区的全球合作至关重要。”。

It is anticipated that it will take up to five years to complete the trial, followed by data analysis and then preparation for submission of data to regulatory authorities.

预计完成试验将需要五年时间，然后进行数据分析，然后准备向监管机构提交数据。

In GSK's Phase 2b trial, M72/AS01E provided approximately 50% protection (13/1626 versus 26/1663) against progression to active pulmonary tuberculosis for three years in Mycobacterium tuberculosis-infected HIV-negative adults, which was unprecedented in decades of TB vaccine research. The World Health Organization estimates that over a 25-year time span, that level of protection could save 8.5 million lives, prevent 76 million new TB cases and save $41.5 billion for TB affected households..

在GSK的2b期试验中，M72/AS01E在结核分枝杆菌感染的HIV阴性成年人中提供了大约50%的保护（13/1626对26/1663），可以防止三年内发展为活动性肺结核，这在数十年的结核病疫苗研究中是前所未有的。世界卫生组织估计，在25年的时间跨度内，这一保护水平可以挽救850万人的生命，预防7600万新的结核病病例，并为受结核病影响的家庭节省415亿美元。。

About the Bill & Melinda Gates Medical Research Institute (Gates MRI)The Bill & Melinda Gates Medical Research Institute is a non-profit medical research organization dedicated to the development and effective use of novel biomedical interventions addressing substantial global health concerns, for which investment incentives are limited, including malaria, tuberculosis, enteric and diarrheal diseases, and diseases that impact maternal, newborn, and child health.

关于比尔和梅琳达·盖茨医学研究所（盖茨MRI）比尔和梅琳达·盖茨医学研究所是一家非营利性医学研究组织，致力于开发和有效使用新型生物医学干预措施，解决全球重大健康问题，投资激励措施有限，包括疟疾，结核病，肠道和腹泻疾病，以及影响孕产妇、新生儿和儿童健康的疾病。

For further information please visit www.gatesmri.org..

欲了解更多信息，请访问www.gatesmri.org。。

For more information, contact: media@gatesmri.org

有关更多信息，请联系：media@gatesmri.org

SOURCE Bill & Melinda Gates Medical Research Institute

来源：比尔和梅琳达·盖茨医学研究所