Delamanid

LOS ANGELES, Nov. 14, 2024 (GLOBE NEWSWIRE) -- ACTG, a global clinical trials network focused on HIV and other infectious diseases, announced two oral presentations on tuberculosis (TB) therapy that took place at The Union Conference on Lung Health 2024, in Bali, Indonesia. The oral presentation “Six Months is a Lot of Time to Lie:” Disclosure and Treatment Preferences Among Participants in a Tuberculosis Therapeutic Trial was presented by Faith Mugodhi, M.Sc., H.S.W., University of Zimbabwe-Clinical Trials Research Centre (UZ-CTRC). The oral presentation High Prevalence of Fluoroquinolone Resistance and katG Mutations in Adult Index Patients in a Multinational MDR-TB Prevention Trial was presented by Soyeon Kim, Sc.D., IMPAACT Senior Statistician, Frontier Science Foundation. “ACTG is honored to share these important findings with the many global stakeholders who are gathered in Indonesia at the Union Conference,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles. “TB is one of ACTG’s key research priorities, as the disease remains a leading killer worldwide. The knowledge gained from the research presented today has the potential to inform our approach to TB treatment and ultimately improve the experiences of people with TB.” “Six Months is a Lot of Time to Lie:” Disclosure and Treatment Preferences Among Participants in a Tuberculosis Therapeutic Trial was a sub-study that investigated experiences around disclosure and treatment preferences among participants in ACTG 5362. Also known as CLO-FAST, this multi-center treatment-shortening trial for drug-susceptible TB randomized individuals to receive either a three-month regimen containing clofazimine (which can be associated with skin hyperpigmentation) or the six-month standard of care. The sub-study consisted of exploratory, qualitative in-depth interviews with 23 participants undergoing treatment in CLO-FAST from India, Malawi, and Zimbabwe. This presentation reported that all sub-study participants with TB had voluntarily disclosed their TB status to at least one other person. Nearly half of participants (43.5 percent) feared inadvertent disclosure of their status due to their treatment and attendance at the TB clinic; 80 percent (n=8) of these were taking clofazimine. One in five participants reported experiencing stigma or discrimination as a result of inadvertent disclosure, including being treated badly by their families or communities. Today’s presentation also found that participants had different preferences around the kind of treatment they received. Two-thirds (n=15) of participants reported that they would prefer the shortened regimen even if one of the medications led to a change in their skin color, while one-third (n=8) reported a preference for the longer regimen. That preference was associated with anticipation of stigma and beliefs that a longer regimen is more potent against TB. These data suggest that anticipated stigma and pre-existing beliefs may be important in understanding treatment preferences. High Prevalence of Fluoroquinolone Resistance and katG Mutations in Adult Index Patients in a Multinational MDR-TB Prevention Trial is an analysis from the PHOENIx study, an ongoing clinical trial evaluating the efficacy and safety of preventive treatment for multi-drug resistant TB (MDR-TB) with delamanid compared to isoniazid, conducted jointly by the ACTG and IMPAACT (International Maternal Pediatric Adolescent AIDS Clinical Trials) networks. (IMPAACT is a global collaboration of investigators, institutions, community representatives, and other partners, with a mission to improve health outcomes for infants, children, and adolescents as well as pregnant and postpartum people who are impacted by or living with HIV by evaluating novel treatments and interventions for HIV and its complications for tuberculosis and other related complications, through the conduct of high-quality clinical trials.) Knowledge of drug susceptibility in people with active TB is important for the provision of both efficacious treatment for their TB disease and TB preventive treatment for their contacts. This presentation sought to describe drug resistance patterns in adults with MDR-TB whose household members were approached to participate in PHOENIx. Between June 2019 and October 2023, 1,353 adults with documented MDR-TB were enrolled from 28 sites and 13 countries in Africa, Asia, and Central and South America. Among those for whom isoniazid mutation data were available, 73 percent (n=783 of 1078) had high-level resistance (katG mutations). Among the 699 participants who had fluoroquinolone drug-susceptibility testing available, 20 percent (n=139) had fluoroquinolone resistance. These results suggest that it is important to have non-fluoroquinolone options for TB preventive treatment. They also support the relevance of the PHOENIx trial’s evaluation of delamanid vs. isoniazid for TB preventive treatment in high-risk household contacts of adults with MDR-TB. Primary results of the clinical trial are anticipated in 2027. CLO-FAST is led by John Metcalfe, M.D., Ph.D., M.P.H., University of California San Francisco; Samuel Pierre, M.D., Les Centres Gheskio, Haiti; and Kimberly Scarsi, Pharm.D., M.S., University of Nebraska Medical Center and study drugs were supplied by the Global Drug Facility. PHOENIx is jointly conducted by ACTG and IMPAACT and led by Gavin Churchyard M.B.Ch.B., M.Med., Ph.D., The Aurum Institute NPC; Amita Gupta, M.D., M.H.S., Johns Hopkins University; Anneke Hesseling, M.B.Ch.B., M.Sc., Ph.D., Desmond Tutu TB Centre - Stellenbosch University; and Susan Swindells, M.B.B.S., University of Colorado. Delamanid is supplied for PHOENIx by Otsuka Pharmaceutical Company, Ltd. ACTG is led by Dr. Currier and Joseph J. Eron, M.D., University of North Carolina (ACTG Vice-Chair). The studies are sponsored by the National Institute of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID, which also funds ACTG) under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. IMPAACT is also funded by NIAID with support and co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH). About ACTGACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at hundreds of locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve. Disclaimer: This content is solely the responsibility of ACTG and does not necessarily represent the official views of the NIH. Media Contact:Jenna Conley, ACTGjenna@conleycommunications.net

Otsuka Pharmaceutical, Co. Ltd. And our U.S.-based subsidiary Otsuka Pharmaceutical Development & Commercialization, Inc., announce that interim data from a Phase 2b/c trial exploring quabodepistat (QBS), in combination with delamanid and bedaquiline, for the treatment of pulmonary tuberculosis (TB) is positive and may shorten the duration of TB treatment for patients. QBS is an investigational anti-tuberculosis compound which has a new mechanism of action that interferes with the cell-wall structure of the bacteria causing TB.1,2 Worldwide, TB is the second leading infectious fatal disease after COVID-19. The interim analysis -- which was presented at the 2024 Conference on Retroviruses and Opportunistic Infections in Denver, Colorado in early March -- demonstrated that a four-month regimen of QBS, in combination with delamanid and bedaquiline, can achieve similar safety and efficacy, compared to the six-month, standard-of-care four-drug regimen in participants with drug-susceptible TB.3 These results show that sputum culture conversion rates -- or effectiveness of the treatment combination in killing the bacteria -- at the end of treatment in the pooled QBS-based, three-drug regimen arms were on par with existing standard four-drug TB treatment. The three-drug QBS-based arms were well-tolerated, with no serious treatment emergent adverse events reported, related to the regimens.3 The ongoing study, supported by Otsuka and the Bill & Melinda Gates Foundation, is being held across six clinical research sites in South Africa. Otsuka and the foundation have been collaborating to end TB worldwide, and the foundation contributed to initial funding for the early development of quabodepistat.2,3 "Otsuka is encouraged by these positive interim data and is pleased to continue working with the support of the Bill & Melinda Gates Foundation to identify safe and effective treatment options for patients living with tuberculosis," said Masanori Kawasaki, global project leader of TB Project at Otsuka Pharmaceutical. "We are deeply thankful to the patients, their families and the clinicians who participated in this important clinical research study." The trial (NCT05221502) was a multicenter, Phase 2b/c, open-label, randomized, dose-finding trial designed to evaluate the safety and efficacy of a four-month regimen of OPC-167832 (quabodepistat) in combination with delamanid and bedaquiline in patients with drug-susceptible pulmonary tuberculosis in comparison with six months standard treatment. Full results of this phase 2b/c, randomized trial are expected by the end of 2024.2,3 *1Hariguchi N et al. OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor. Antimicrob Agents Chemother. 2020 May 21;64(6):e02020-19. *2Dawson R et al. Quabodepistat in Combination with Delamanid and Bedaquiline in Participants with Drug-Susceptible Pulmonary Tuberculosis: protocol for a multicenter, phase 2 b/c, open-label, randomized, dose-finding trial to evaluate safety and efficacy. Trials. 2024 Jan 19;25(1):70. *3Dawson R et al. A 4-month Regimen of Quabodepistat, Delamanid and Bedaquiline for Pulmonary TB: Interim Results. Conference on Retroviruses and Opportunistic Infections (CROI), 5 March 2024, Denver, Co., USA; Abstract no. 163. *4World Health Organization, Tuberculosis key facts　https://www.who.int/news-room/fact-sheets/detail/tuberculosis