PRISM-TB is an international, multicenter, open-label, randomized, controlled, pragmatic, stratified medicine, treatment shortening, noninferiority Phase 3 clinical trial for fluoroquinolone-susceptible multidrug-resistant/rifampin-resistant pulmonary tuberculosis (FQ-S MDR/RR-TB).
The trial objective is to evaluate whether stratified medicine treatment strategies for FQ-S MDR/RR-TB, defined by a pre-specified risk stratification algorithm, have noninferior efficacy to a one-size-fits-all control regimen (the local standard-of-care [SOC] regimen consistent with preferred regimen(s) in international guidelines), as measured by TB-related unfavorable outcomes at Week 73.

Start Date01 Nov 2024

Sponsor / Collaborator

The University of California, San Francisco

[+1]

NCT06192160 / Not yet recruitingPhase 2IIT

A Phase 2 Randomized, Adaptive, Dose-Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis

A5409/RAD-TB is an adaptive Phase 2 randomized, controlled, open-label, dose-ranging, platform protocol to evaluate the safety and efficacy of multidrug regimens for the treatment of adults with drug-susceptible pulmonary tuberculosis (TB).
A5409 hypothesizes that novel regimens for the treatment of pulmonary tuberculosis will result in superior early efficacy, as determined by longitudinal mycobacteria growth indicator tube (MGIT) liquid culture time to positivity (TTP) measurements over the first 6 weeks of treatment, and will have acceptable safety and tolerability over 8 weeks of treatment relative to standard of care [(SOC) isoniazid/rifampicin/pyrazinamide/ethambutol (HRZE)].
The study will run for 52 weeks, inclusive of 26 weeks of TB treatment comprised of 8 weeks of experimental or SOC treatment (based on treatment arm assignment) followed by 18 weeks of SOC treatment with 45 participants in each experimental treatment arm and at least 90 participants in the SOC arm.

Start Date15 Sep 2024

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

[+1]

CTR20240602 / CompletedNot Applicable

富马酸贝达喹啉片在中国健康受试者中的随机、开放、单次给药、两制剂、空腹两周期双交叉的生物等效性研究。

[Translation] A randomized, open-label, single-dose, two-formulation, two-period fasting, double-crossover bioequivalence study of bedaquiline fumarate tablets in Chinese healthy subjects.

以中国健康受试者为试验对象，采用自身交叉对照的试验设计，测定中诺凯琳健康产业（海南）有限公司持证，华益泰康药业股份有限公司生产的富马酸贝达喹啉片给药后的血浆中贝达喹啉在健康受试者体内的血药浓度经时过程，估算相应的药代动力学参数，并以Janssen-Cilag International NV持证，Janssen Pharmaceutica NV生产的富马酸贝达喹啉片（商品名：Sirturo®，规格：100 mg）为参比，评价制剂间的生物等效性，并观察富马酸贝达喹啉片在中国健康受试者中的安全性。

[Translation]

Healthy Chinese subjects were used as the experimental subjects. A self-crossover experimental design was adopted to determine the time course of plasma concentration of bedaquiline in healthy subjects after administration of bedaquiline fumarate tablets, which are licensed by Sinocare Health Industry (Hainan) Co., Ltd. and produced by Huayi Taikang Pharmaceutical Co., Ltd., and to estimate the corresponding pharmacokinetic parameters. Bedaquiline fumarate tablets (trade name: Sirturo®, specification: 100 mg), which are licensed by Janssen-Cilag International NV and produced by Janssen Pharmaceutica NV, were used as the reference to evaluate the bioequivalence between the preparations and to observe the safety of bedaquiline fumarate tablets in healthy Chinese subjects.

Start Date25 Feb 2024

Sponsor / Collaborator

Best Medicine Co., Ltd.

100 Clinical Results associated with Bedaquiline Fumarate

100 Translational Medicine associated with Bedaquiline Fumarate

100 Patents (Medical) associated with Bedaquiline Fumarate

1,300

Literatures (Medical) associated with Bedaquiline Fumarate

31 Dec 2024·Global health action

Low body mass index as a predictor of sputum culture conversion and treatment outcomes among patients receiving treatment for multidrug-resistant tuberculosis in Lesotho

Article

Author: Maime, Refiloe ; Makaka, Joalane ; Kunda, Mikanda ; Seung, K J ; Kanu, Makelele ; Maama, Llang ; Franke, Molly F ; Mpinda, Stephanie ; Mofolo, Mabatloung ; Oyewusi, Lawrence ; Senyo, Ninza ; Mitnick, Carole D ; Mayombo, Lwayi ; Oguntoyinbo, Bamidele ; Zeng, Chengbo ; Tamirat, Meseret

BACKGROUND:

A low body mass index (BMI) at the start of treatment for rifampicin- or multidrug-resistant tuberculosis (MDR/RR-TB) is associated with poor treatment outcomes and may contribute to delayed sputum culture conversion, thereby prolonging the period of potential transmission to others. Whether the relative importance of low BMI in predicting treatment outcomes differs by HIV status is unclear.

OBJECTIVES:

We evaluated the association between low BMI and two dependent variables, sputum culture conversion and end-of-treatment outcome, among patients receiving treatment for MDR/RR-TB in Lesotho, a setting with a high prevalence of HIV infection.

METHODS:

Secondary data from a prospective cohort of patients initiating a longer (18-20 months) treatment containing bedaquiline and/or delamanid under routine programmatic conditions in Lesotho were analysed. Risk ratios and differences were adjusted for potential confounders using multivariable logistic regression, and estimates were stratified by HIV status.

RESULTS:

Of 264 patients, 105 and 250 were eligible for culture conversion and end-of-treatment analyses, respectively. Seventy-one per cent of patients (74/105) experienced culture conversion within six months, while 74% (184/250) experienced a favourable end-of-treatment outcome. Low BMI was associated with a lower frequency of culture conversion at six months among those who were not living with HIV (relative risk [RR]: 0.50 [95% CI: 0.21, 0.79]); this association was attenuated among those living with HIV (RR: 0.88 [95% CI: 0.68, 1.23]). A low BMI was moderately associated with a lower frequency of treatment success (RR = 0.89 [95% CI: 0.77, 1.03]), regardless of HIV status.

CONCLUSIONS:

Low BMI was common and associated with the frequency of six-month culture conversion and end-of-treatment outcomes. The association with culture conversion was more pronounced among those not living with HIV. Addressing the myriad factors that drive low BMI in this setting could hasten culture conversion and improve end-of-treatment outcomes. This will require a multipronged approach focused on alleviating food insecurity and enabling prompt diagnosis and treatment of HIV and TB.

01 Mar 2024·Tuberculosis (Edinburgh, Scotland)

The use of Mycobacterium tuberculosis H37Ra-infected immunocompetent mice as an in vivo model of persisters

Article

Author: Chandra, Gyan ; Krishnan, Manju Y ; Ali, Juned ; Sharma, Romil ; Kumari, Neetu ; Singh, Sarika

Persistence of Mycobacterium tuberculosis (Mtb) is one of the challenges to successful treatment of tuberculosis (TB). In vitro models of non-replicating Mtb are used to test the efficacy of new molecules against Mtb persisters. The H37Ra strain is attenuated for growth in macrophages and mice. We validated H37Ra-infected immunocompetent mice for testing anti-TB molecules against slow/non-replicating Mtb in vivo. Swiss mice were infected intravenously with H37Ra and monitored for CFU burden and histopathology for a period of 12 weeks. The bacteria multiplied at a slow pace reaching a maximum load of ∼10⁶ in 8-12 weeks depending on the infection dose, accompanied by time and dose-dependent histopathological changes in the lungs. Surprisingly, four-weeks of treatment with isoniazid-rifampicin-ethambutol-pyrazinamide combination caused only 0.4 log₁₀ and 1 log₁₀ reduction in CFUs in lungs and spleen respectively. The results show that ∼40 % of the H37Ra bacilli in lungs are persisters after 4 weeks of anti-TB therapy. Isoniazid/rifampicin monotherapy also showed similar results. A combination of bedaquiline and isoniazid reduced the CFU counts to <200 (limit of detection), compared to ∼5000 CFUs by isoniazid alone. The study demonstrates an in vivo model of Mtb persisters for testing new leads using a BSL-2 strain.

01 Mar 2024·International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

Second-line antituberculosis drug exposure thresholds predictive of adverse events in multidrug-resistant tuberculosis treatment

Article

Author: Alffenaar, Jan-Willem ; Wang, Shanshan ; Zhu, Yue ; Schön, Thomas ; Niward, Katarina ; Shao, Ge ; Wang, Sainan ; Xu, Chunhua ; Bruchfeld, Judith ; Zhu, Limei ; Zhang, Haoyue ; Cao, Jiayi ; Forsman, Lina Davies ; Xiong, Haiyan ; Hu, Yi

OBJECTIVES:

This study aimed to investigate the association between drug exposure and adverse events (AEs) during the standardized multidrug-resistant tuberculosis (MDR-TB) treatment, as well as to identify predictive drug exposure thresholds.

METHODS:

We conducted a prospective, observational multicenter study among participants receiving standardized MDR-TB treatment between 2016 and 2019 in China. AEs were monitored throughout the treatment and their relationships to drug exposure (e.g., the area under the drug concentration-time curve from 0 to 24 h, AUC_{0-24 h}) were analyzed. The thresholds of pharmacokinetic predictors of observed AEs were identified by boosted classification and regression tree (CART) and further evaluated by external validation.

RESULTS:

Of 197 study participants, 124 (62.9%) had at least one AE, and 15 (7.6%) experienced serious AEs. The association between drug exposure and AEs was observed including bedaquiline, its metabolite M2, moxifloxacin and QTcF prolongation (QTcF >450 ms), linezolid and mitochondrial toxicity, cycloserine and psychiatric AEs. The CART-derived thresholds of AUC_{0-24 h} predictive of the respective AEs were 3.2 mg·h/l (bedaquiline M2); 49.3 mg·h/l (moxifloxacin); 119.3 mg·h/l (linezolid); 718.7 mg·h/l (cycloserine).

CONCLUSIONS:

This study demonstrated the drug exposure thresholds predictive of AEs for key drugs against MDR-TB treatment. Using the derived thresholds will provide the knowledge base for further randomized clinical trials of dose adjustment to minimize the risk of AEs.

News (Medical) associated with Bedaquiline Fumarate

25 Mar 2024

·www.prnewswire.com

New PeerLINC Knowledge Hub will Leverage Local Expertise and Experience to Accelerate New, More Effective TB Cures Around the World

Hub will focus on supporting global use of new treatments that effectively treated drug-resistant TB in 98% of Filipino participants MANILA, Australia, March 24, 2024 /PRNewswire/ -- TB Alliance's new Peer-to-Peer Learning for Innovative Cures (PeerLINC) Knowledge Hub launched today in Manila, with funding from the Australian Government through the Partnerships for a Healthy Region initiative. PeerLINC, operating in partnership between TB Alliance and the Tropical Disease Foundation, Inc. (TDF), and in close collaboration with the Department of Health, Philippines, will help countries implement best practices in the treatment of drug-resistant tuberculosis (DR-TB) to help speed the worldwide programmatic implementation of innovative, more effective treatments for the disease, starting with the World Health Organization (WHO)-recommended six-month, all-oral BPaL/M regimens, composed of the antibiotics bedaquiline (B), pretomanid (Pa), and linezolid (L), with or without moxifloxacin (M). PeerLINC will provide practical training and technical assistance to countries to support this objective, via experts from the Philippines and the Department of Health, including Lung Center of the Philippines and the National TB Reference Laboratory (NTRL). The Philippines has successfully and rapidly deployed new treatments through participation in TB Alliance's Leveraging Innovation for Faster TB Treatment (LIFT-TB) initiative. "TB Alliance works to minimize the gap between research and access, ensuring people anywhere in the world can have access to new treatments as soon as possible, maximizing the number of lives and livelihoods saved," said Sandeep Juneja, Senior Vice President of Market Access at TB Alliance. "PeerLINC will make training and knowledge on new treatments available swiftly and efficiently to ensure their rapid adoption and roll out. We are proud to launch PeerLINC in the Philippines with DOH and TDF and establish the first Knowledge Hub on the introduction of new DR-TB regimens, and we are grateful for the support of Australia in helping make this a reality." "It is important for the Philippines to share our knowledge and experience in using the BPaL/M regimens," said Dr. Mamel Quelapio, TDF Board of Trustees member and Programmatic Implementation Lead at PeerLINC. "DOH's leadership through the Disease Prevention and Control Bureau in partnership with TDF and TB Alliance in the LIFT-TB initiative has led to improved outcomes and treatment experiences for people. We are eager to help new treatments reach far and wide." The BPaL/M regimens combine the antibiotics bedaquiline (B), pretomanid (Pa), linezolid (L) with or without moxifloxacin (M). The BPaL regimen was first clinically studied by TB Alliance and the BPaL/M regimens are now recommended by WHO as the standard of care treatment for the vast majority of people with DR-TB. Prior to the initial study of the BPaL regimen, global treatment success rates for DR-TB were less than 50% and treatment options were limited, expensive, toxic, and lengthy – requiring individuals to take more than 14,000 pills over the course of treatment, which could last from nine months to two years or longer. Data to date reveals treatment success rates of 90% or higher with BPaL/M, in addition to reduced treatment duration and approximately 95% lower pill burden. TB Alliance's LIFT-TB initiative, which is co-funded by GDEF/KOICA, the South Korean Development agency, helped accelerate implementation of the regimen in the Philippines, Indonesia, Kyrgyzstan, Myanmar, Ukraine, Uzbekistan, and Vietnam. Interim data from these countries shows an average success rate of 92.5%, with the Philippines program reporting a 98% cure rate. Several key high-burden countries around the world, including the early adopting LIFT-TB countries, are now rolling out BPaL/M in their national programs. However, some countries have moved more slowly. Leveraging a group of experts and the experience garnered from those who have rapidly and successfully implemented the BPaL/M regimens, PeerLINC will focus on assisting other countries in doing the same. "In the Philippines, the new regimen exceeded all expectations," said Dr. Irene Flores, Medical Officer of the Jose B. Lingad Memorial Medical Center and Head of PeerLINC. "Every country with drug-resistant TB can benefit from widespread implementation of the best available TB treatment. With BPaL/M, we see a path toward transforming DR-TB treatment for everybody, anywhere in the world." "I tried everything before I was given BPaL as part of the research program," said Joegene Mangilaya, a participant from the Philippines who was treated with the BPaL regimen. "I was losing hope that I'd be cured, but shortly after I started on this new regimen, my body felt stronger and I had a new hope for my health and future. It is important to speed the availability of life-saving new therapies everywhere they are needed – the work of PeerLINC will help save lives." PeerLINC will offer support such as advice, assistance, training materials, tools, guides, and other materials to TB programs, clinicians, lab specialists, and community organizations, all delivered through peer-to-peer learning models. Trainings will be provided in-person in the Philippines or in the beneficiary country or remotely through virtual meetings. The expert team from PeerLINC will continue to guide countries after trainings, as they work to implement the regimens. A delegation from Peru is scheduled to visit PeerLINC in April 2024 and will be the first to receive training on BPaL/M from PeerLINC and its partners in the DOH. "We are excited to visit the PeerLINC Knowledge Hub and work with experts from the early implementers of the short, highly effective treatments for drug-resistant tuberculosis," said Dr. Valentina Alarcón, Executive Director at the Directorate of Tuberculosis Prevention and Control - MINSA Peru. "The communities affected by resistant tuberculosis in Peru deserve the best possible experiences and treatment schemes and we are taking measures to access the BPaL and BPaL/M regimens and make them available to people throughout Peru in a timely and rapid manner. Our experience with PeerLINC will help us achieve those goals." About TB TB is a difficult infection to cure, requiring patients to take a combination of medicines for at least four to six months. Even after symptoms disappear, medicines still need to be taken so that the disease can be fully eradicated. The scope and intensity of TB globally is in large part fueled by antiquated and inadequate TB drugs. Novel drug regimens are urgently needed to bring the TB pandemic under control. About BPaL The BPaL regimen—which combines the antibiotics bedaquiline (B), pretomanid (Pa), and linezolid (L)—was first designed and clinically studied by TB Alliance. Pretomanid, as part of the BPaL regimen, received its first regulatory approval in August 2019 for use against highly drug-resistant strains of TB. Prior to the initial BPaL clinical trial, less than one-third of drug-resistant TB patients around the world were being successfully treated. Treatment options were limited, expensive, toxic, and lengthy – requiring patients to take more than 20 pills per day for 9-20 months. About TB Alliance TB Alliance is a not-for-profit organization dedicated to finding faster-acting and affordable drug regimens to fight TB. Through innovative science and with partners around the globe, we aim to ensure equitable access to faster, better TB cures that will advance global health and prosperity. TB Alliance operates with support from Australia's Department of Foreign Affairs and Trade, Bill & Melinda Gates Foundation, Foreign, Commonwealth and Development Office (United Kingdom), Cystic Fibrosis Foundation, Germany's Federal Ministry of Education and Research through KfW, Global Disease Eradication Fund (South Korea), Global Health Innovative Technology Fund, Irish Aid, Korea International Cooperation Agency, National Institute of Allergy and Infectious Diseases, South Korea's Ministry of Foreign Affairs, Unitaid, and the United States Agency for International Development. For more information, please visit: . Contact: Jessica Wiggs, +1 (646) 616-8613 / [email protected] SOURCE TB Alliance

Drug ApprovalClinical Study

24 Mar 2024

·www.prnewswire.com

Australian Government Grants TB Alliance an Award to Help Bolster Clinical Research and Improve Access to New Treatments for Drug-Resistant TB

AUD 17 Million Grant over 5 Years Will Fund Next-Generation TB Cures CANBERRA, Australia, March 24, 2024 /PRNewswire/ -- The Australian Government, through the Partnerships for a Healthy Region initiative, has announced a new AUD 17 million grant to support work with TB Alliance through its Product Development and Access Partnerships program. The funding will contribute toward the completion of the NC-009 Pan-Phase 2 clinical trial and also help establish and sustain the Peer-to-Peer Learning for Innovative Cures (PeerLINC) Knowledge Hub in Manila, which will disseminate best practices to help speed the programmatic implementation of innovative, effective tuberculosis treatments, including the World Health Organization (WHO) recommended six-month, all-oral BPaL/M regimens for drug-resistant tuberculosis (DR-TB). "Drug-resistant TB is an increasing threat to the health and well-being both in Australia and in our neighbouring countries, and in many low- and middle-income countries around the world," said the Hon. Pat Conroy, Minister for International Development and the Pacific. "We are proud of our continued support of the work of TB Alliance, and to help in the rollout of the BPaL/M regimens and to support the development of the next generation of new TB treatments. These are important steps in the effort to end TB as a major health threat by 2030." PeerLINC, which will operate in partnership between TB Alliance and the Tropical Disease Foundation, Inc., will provide practical training, guidance, technical support, field experience, tools, and materials to national TB programs covering a wide range of topics including clinical management, diagnostics, drug safety monitoring, programmatic management, community engagement, and health economics. PeerLINC will continue to guide countries after completion of initial training, as countries work to implement and integrate the BPaL/M regimens into their national tuberculosis programs. The NC-009 trial, which launched in November 2023, will evaluate the safety and efficacy of a combination of a new experimental compound, TBAJ-876, with pretomanid and linezolid, components of the BPaL regimen. This new combination has the potential to shorten and improve treatment for both drug-sensitive and drug-resistant tuberculosis (TB). Results from preclinical and Phase 1 studies presented at the Union Conference showed that TBAJ-876, when compared to bedaquiline (an approved TB medicine in the same drug class), eliminated TB bacteria faster and had a potentially improved safety profile. "Australia has long been a leader in the global health community, and we greatly appreciate their unwavering support in the battle to end TB," said Dr. Mel Spigelman, President and CEO of TB Alliance. "This funding will contribute both to rapidly expanding access to improved treatments, and also to developing the next generation of even more effective TB cures. This award exemplifies the sort of global commitment and political will needed if we hope to, one day, end the TB pandemic." About TB TB is a difficult infection to cure, requiring patients to take a combination of medicines for at least four to six months. Even after symptoms disappear, medicines still need to be taken so that the disease can be fully eradicated. The scope and intensity of TB globally is in large part fueled by antiquated and inadequate TB drugs. Novel drug regimens are urgently needed to bring the TB pandemic under control. About BPaL The BPaL regimen—which combines the antibiotics bedaquiline (B), pretomanid (Pa), and linezolid (L)—was first designed and clinically studied by TB Alliance. Pretomanid, as part of the BPaL regimen, received its first regulatory approval in August 2019 for use against highly drug-resistant strains of TB. Prior to the initial BPaL clinical trial, less than one -third of drug-resistant TB patients around the world were being successfully treated. Treatment options were limited, expensive, toxic, and lengthy – requiring patients to take more than 20 pills per day for 9-20 months. About TB Alliance TB Alliance is a not-for-profit organization dedicated to finding faster-acting and affordable drug regimens to fight TB. Through innovative science and with partners around the globe, we aim to ensure equitable access to faster, better TB cures that will advance global health and prosperity. TB Alliance operates with support from Australia's Department of Foreign Affairs and Trade, Bill & Melinda Gates Foundation, Foreign, Commonwealth and Development Office (United Kingdom), Cystic Fibrosis Foundation, Germany's Federal Ministry of Education and Research through KfW, Global Disease Eradication Fund (South Korea), Global Health Innovative Technology Fund, Irish Aid, Korea International Cooperation Agency, National Institute of Allergy and Infectious Diseases, South Korea's Ministry of Foreign Affairs, Unitaid, and the United States Agency for International Development. For more information, please visit: . Contact: Jessica Wiggs, +1 (646) 616-8613 / [email protected] SOURCE TB Alliance

Phase 1Phase 2

16 Nov 2023

·www.prnewswire.com

TB Alliance Launches Five-Country Phase 2 Clinical Trial Evaluating Next-Generation TB Drug

Early results presented at the Union World Conference on Lung Health suggest promise of new compound to fight tuberculosis that will be tested as part of Phase 2 trial The first participant has been dosed in this partially double-blind study to evaluate the safety and efficacy of what has the potential to be a "universal regimen" to treat TB PARIS, Nov. 16, 2023 /PRNewswire/ -- TB Alliance launched a new Pan-Phase 2 clinical trial incorporating elements of Phase 2a, b and c, identified as NC-009, to evaluate the safety and efficacy of a combination of a new experimental compound, TBAJ-876, with pretomanid and linezolid, components of TB Alliance's BPaL regimen. This regimen has the potential to shorten and improve treatment for both drug-sensitive and drug-resistant tuberculosis (TB)—one of the world's deadliest infectious diseases. Results from preclinical and Phase 1 studies presented at the Union Conference showed that the new compound, when compared with bedaquiline (a TB medicine in the same drug class), eliminated TB bacteria faster and had a potentially safer profile. "A 'universal' TB medicine needs to be highly effective while causing very few adverse effects; initial Phase 1 trial results show that TBAJ-876 could possibly move the needle in this direction," said Dr. Mel Spigelman, President and CEO of TB Alliance. "If we can develop a regimen that is composed of novel compounds with minimal pre-existing resistance that is both highly potent and safe, it could blur the distinction between drug-sensitive and drug-resistant TB allowing for treatment of virtually all patients with active TB with the same regimen." The new trial, NC-009, will test different doses of TBAJ-876 in combination with pretomanid and linezolid against the current standard of care for drug-sensitive TB—isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE). Another arm of the trial will also test pretomanid and linezolid in combination with bedaquiline (BPaL), a regimen recommended by the World Health Organization to treat some forms of drug-resistant TB, against drug-sensitive TB. The study aims to enroll 300 participants with drug-sensitive TB at 21 clinical trial sites in five countries: Georgia, Philippines, South Africa, Tanzania, and Uganda. "To truly get ahead of the tuberculosis pandemic in all of its forms, we need to continually innovate," said Dr. Francesca Conradie, Principal Investigator for the NC-009 clinical trial in South Africa. "Recent innovations in drug-resistant TB therapy have been enormously important, but we need to continue to develop shorter, simpler, and more people-friendly cures, including in drug-sensitive TB where there hasn't been a new drug approved in more than 50 years." New Experimental Compound TBAJ-876 is a diarylquinoline, a category of antibiotic that targets a key enzyme of the tuberculosis bacteria involved in energy production. Bedaquiline, a TB drug approved for the treatment of drug-resistant TB by the US FDA in 2012, is in the same diarylquinoline drug class. At the Union Conference in Paris, data were presented—showing that the new experimental compound has the potential to become an important component in TB regimens moving forward: In in vitro studies, TBAJ-876 demonstrated anti-mycobacterial activity approximately 10-fold greater than bedaquiline. In mouse models of TB, TBAJ-876, together with pretomanid and linezolid, cured infections with shorter treatment durations than HRZE and BPaL regimens. TBAJ-876 also demonstrates greater activity against TB strains resistant to bedaquiline (Rv0678 mutants), suggesting it will also be more effective in treating these emerging strains. In preclinical studies, TBAJ-876 showed the potential to be safer than bedaquiline, including low potential for QT prolongation. In Phase 1 studies involving 165 healthy subjects, few, generally mild, adverse events were observed. About TB TB is a difficult infection to cure, requiring patients to take a combination of medicines for at least four to six months. Even after symptoms disappear, medicines still need to be taken so that all traces of the disease can be fully eradicated. The scope and intensity of TB globally is in large part fueled by antiquated and inadequate TB drugs. Novel drug regimens are urgently needed to bring the TB pandemic under control. About BPaL The BPaL regimen—which combines the antibiotics bedaquiline (B), pretomanid (Pa), and linezolid (L)—was first clinically studied by TB Alliance. Pretomanid, as part of the BPaL regimen, received its first regulatory approval in August 2019 for use against highly drug-resistant strains of TB. Previously, less than two-thirds of drug-resistant TB patients around the world had been successfully treated. Treatment options were limited, expensive, toxic, and lengthy – requiring patients to take more than 20 pills per day for 9-20 months. About TB Alliance TB Alliance is a not-for-profit organization dedicated to finding faster-acting and affordable drug regimens to fight TB. Through innovative science and with partners around the globe, we aim to ensure equitable access to faster, better TB cures that will advance global health and prosperity. TB Alliance operates with support from Australia's Department of Foreign Affairs and Trade, Bill & Melinda Gates Foundation, Foreign, Commonwealth and Development Office (United Kingdom), Cystic Fibrosis Foundation, Germany's Federal Ministry of Education and Research through KfW, Global Disease Eradication Fund (South Korea), Global Health Innovative Technology Fund, Irish Aid, Korea International Cooperation Agency, National Institute of Allergy and Infectious Diseases, South Korea's Ministry of Foreign Affairs, Unitaid, and the United States Agency for International Development. For more information, please visit: . Contact: Jess Wiggs, [email protected], +1 240 425 7117 SOURCE TB Alliance

Phase 1Phase 2Drug ApprovalClinical Result

100 Deals associated with Bedaquiline Fumarate

External Link

KEGG	Wiki	ATC	Drug Bank
D09873	Bedaquiline Fumarate	J04AK05	DB08903

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Pulmonary Tuberculosis	JP	Janssen Pharmaceutical KK	19 Jan 2018
Tuberculosis	KR	Janssen Korea Co. Ltd.	21 Mar 2014
Tuberculosis, Multidrug-Resistant	US	Janssen Therapeutics, Inc.	28 Dec 2012

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Mycobacterium Avium-Intracellulare Infection	Phase 3	JP	Janssen Pharmaceuticals, Inc.	08 Jan 2021
Mycobacterium Avium-Intracellulare Infection	Phase 3	KR	Janssen Pharmaceuticals, Inc.	08 Jan 2021
Mycobacterium Avium-Intracellulare Infection	Phase 3	TW	Janssen Pharmaceuticals, Inc.	08 Jan 2021
Extensively Drug-Resistant Tuberculosis	Phase 3	ZA	Global Alliance for TB Drug Development	01 Mar 2015
Infectious Lung Disorder	Phase 3	ZA	Global Alliance for TB Drug Development	01 Mar 2015
Multidrug resistant pulmonary tuberculosis	Phase 3	ZA	Global Alliance for TB Drug Development	01 Mar 2015
Leprosy, Multibacillary	Phase 2	BR	Janssen Research & Development LLC	26 Sep 2018
HIV Infections	Phase 2	PE	National Institute of Allergy & Infectious Diseases	15 Aug 2016
HIV Infections	Phase 2	ZA	National Institute of Allergy & Infectious Diseases	15 Aug 2016
Liver Diseases	Phase 1	-	Tibotec Virco Virology BV	01 Jan 2010

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03338621 (CTgov)	Phase 2/3	Multidrug resistant pulmonary tuberculosis \| Tuberculosis, Multidrug-Resistant	455	ethambutol+rifampicin+isoniazid+pyrazinamide (Drug Sensitive-TB 2HRZE/4HR)	cpodmrdqha(wqvhizzowq) = nkpjkwvvwy aukwszsioq (njivkgwvhf, waljhczhji - feozgfzdyo) View more	-	08 Nov 2023
				4BPaMZ (Drug Sensitive-TB 4BPaMZ)	cpodmrdqha(wqvhizzowq) = agpkeazfiz aukwszsioq (njivkgwvhf, fzinbypqrv - dqnvqokizn) View more
NCT03086486 (ZeNix, CTgov)	Phase 3	Extensively Drug-Resistant Tuberculosis \| Pulmonary Tuberculosis \| Infectious Lung Disorder	181	Placebo Linezolid+Pretomanid+Linezolid+Bedaquiline (1200mg L x 26 Weeks + Pa + B)	hqfnwhhzbg(svzdeqddyl) = osdevrxlgc jegtikibkg (dgxylugffc, lnvoryyifg - xslwvththm) View more	-	29 Jun 2023
				Placebo Linezolid+Pretomanid+Linezolid+Bedaquiline (1200 mg L x 9 Weeks + Pa + B)	hqfnwhhzbg(svzdeqddyl) = fwpxhymrsw jegtikibkg (dgxylugffc, bbxqceqchk - ejquelejhh) View more
NCT03086486 (ZeNix, Pubmed \| Br Dent J)	Phase 3	Drug-Resistant Tuberculosis	181	Bedaquiline-pretomanid-linezolid with linezolid 1200mg for 26 weeks	ajyjlxuvpg(vogsvyxgdn) = the linezolid dose was modified (i.e., interrupted, reduced, or discontinued) in 51%, 30%, 13%, and 13% of participants who received bedaquiline-pretomanid-linezolid with linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks, respectively micxrhpnsc (ewcldacqrh ) View more	Positive	01 Sep 2022
				Bedaquiline-pretomanid-linezolid with linezolid 1200mg for 9 weeks
NCT02454205 (NExT, Pubmed) Manual	Phase 2/3	Tuberculosis, Multidrug-Resistant	93	Levofloxacin+Bedaquiline+Linezolid	flmdokbdlb(pknlsgwmzm) = jyhketiahw zfokzkwrsm (gxhkzecffz ) View more	Positive	17 Feb 2022
				SOC	flmdokbdlb(pknlsgwmzm) = csxmrbqrxn zfokzkwrsm (gxhkzecffz ) View more
NCT02754765 (Pubmed \| Clin Infect Dis)	Phase 3	Pulmonary Tuberculosis \| Tuberculosis, Multidrug-Resistant	2,296	Bedaquiline and/or Delamanid	iwaxaxffmz(ujtquhaurn) = occurred in 36.8% or 72.8 (95%CI: 66.0-80.0) times/1000 person-months of injectable drug exposure fyzuwtqudh (lgstskgtbp ) View more	-	13 Jan 2022
				Linezolid
ERS2021	Not Applicable	Extensively Drug-Resistant Tuberculosis	87	Bedaquiline and fluoroquinolone-based treatment regimens	xbninarnwz(rmrnfzjynx) = agdpjgsyap cnlsyttrzv (tkpabbdurk ) View more	-	05 Sep 2021
ERS2021	Not Applicable	Soft Tissue Infections	-	Bedaquiline	tvjpccaidf(ixadcwfthz) = Side effects included corrected QT prolongation utbvjglkpz (visbcvvrtg ) View more	-	05 Sep 2021
NCT02354014 (TMC207-C211, Pubmed) Manual	Phase 2	Tuberculosis	30	Bedaquiline	yariswlkzj(kljcfjtjfy) = Few esekahsfvi (dcsdfchvua ) View more	Positive	01 Sep 2021
				Bedaquiline (≥12-<18 years)
NCT02583048 (ACTG A5343, Pubmed \| Lancet Infect Dis)	Phase 2	Rifampicin resistant tuberculosis	84	Bedaquiline	uuargjowkj(ersqluhukw) = ynjzuicwxe ocbzgnbrul (rifnpvozwr, 71 - 97)	Positive	12 Feb 2021
				Delamanid	uuargjowkj(ersqluhukw) = oubfvairqa ocbzgnbrul (rifnpvozwr, 65 - 95)
ZeNix (IAS2021)	Not Applicable	Tuberculosis	181	Bedaquiline (B)	hojezrdafw(jfkkdnvkdj) = rqsuvvelda btqgiayqlq (vfyiyqfehh )	-	01 Jan 2021

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