Project Title: A phase IIb, Open-label, Randomized Controlled Dose Ranging Multi-Centre Trial to Evaluate the safety, Tolerability, Pharmacokinetics and Exposure-Response Relationship of different doses of Delpazolid in combination with Bedaquiline Delamanid Moxifloxiacin in adult Subjects with newly diagnosed uncomplicated, Smear-Positive, Drug-Sensitive Pulmonary Tuberculosis Delpazoilid.
Project Description: While progress has been made in recent years in controlling tuberculosis (TB) globally, TB has remained a persistent problem in the developing countries of Africa, Asia and Eastern Europe. TB is the ninth leading cause of death worldwide and the leading cause from a single infectious agent, ranking above HIV/AIDS. The current first-line anti-tubercular agents have been in use for over 20 years and are relatively ineffective in controlling TB as a public health problem.... While progress has been made in recent years in controlling tuberculosis (TB) globally, TB has remained a persistent problem in the developing countries of Africa, Asia and Eastern Europe. TB is the ninth leading cause of death worldwide and the leading cause from a single infectious agent, ranking above HIV/AIDS. The current first-line anti-tubercular agents have been in use for over 20 years and are relatively ineffective in controlling TB as a public health problem. New TB treatment regimens are vital to combat the TB epidemic, and most importantly, the drug resistant TB epidemic. PanACEA has taken the opportunity to build on knowledge derived from NiX-TB, and aims to take steps to test a similar regimen to be used in a larger population of TB patients. PanACEA proposes to investigate the combination of BDM - DZD: BDQ DLM, moxifloxacin (MXF) and DZD. DZD in combination with BDM, is key in advancing a TB regimen with low pre-existing resistance and improved tolerability compared to LZD containing regimens. DZD has a good safety profile, as has been assessed both pre-clinically and clinically for up to 21 days in healthy volunteer. The study sponsor is LegoChem Biosciences, Inc. The trial is conducted under the umbrella of PanACEA, the Pan African Consortium for the Evaluation of anti-TB Antibiotics. LegoChem Biosciences ensures that sufficient funding of this study is available, and will contribute sufficient DZD 400mg tablets Biosciences to ensure conduct of this study. Overall, the primary objective is to describe the safety, tolerability and exposure-toxicity relationship of DZD given over 16 weeks in combination with standard-dose BDQ, DLM and MXF compared to standard-dose BDQ, DLM and MXF alone. The aim is to identify the optimal dose of DZD to be used in subsequent studies that provides the best efficacy at acceptable safety of the drug when given daily over 4 months in patients with newly diagnosed, uncomplicated, smear-positive, drug-sensitive, pulmonary tuberculosis. It will be conducted in Dar es Salaam, Mwananyamala Regional Referral Hospital. The design of the study will be an open label Phase 11b dose-finding, randomized, controlled study with a duration of 16 weeks of experimental therapy of DZD — Bedaquiline/Delamanid/Moxifloxacin (BDM) in adult patients with newly diagnosed, smear positive, uncomplicated, drug sensitive pulmonary tuberculosis (TB) to evaluate the safety, efficacy, tolerability, pharmacokinetics and exposure/response-relationship of different doses of delpazolid in combination with bedaquiline, delamanid and moxifloxacin. Participants will be randomized to one of five arms containing BDM with different doses of DZD. A total of 75 male or female subjects, aged between 18 and 65 years with newly diagnosed, drug sensitive, uncomplicated, smear-positive, pulmonary TB will be included. For analysis, 15 patients per arm with a total of N = 75 patients, and a wide range of DZD doses (from Omg to 800mg BID) has been determined as an adequate sample size for population PK modelling, and for exposure-response modeliing to detect a clinically meaningful dose-dependent relationship. Participants will be randomized to one of five arms containing a BDM backbone with different doses of DZD, ranging from Omg DZD (no DZD present in the regimen) up to 1,600mg (800mg BD). Study treatment intake will be observed by study staff during the study visits in the morning and will be administered at home on the other days. Furthermore, treatment adherence will be assessed by pill counting at every visit. Recruitment can be enhanced by individual and community awareness of the study and/or TB in general, through the following materials, but not limited to these: e Public announcements through advertisements, posters and radio announcements • Information leaflets distributed to healthcare providers, to be handed to newly diagnosed TB patients Written informed consent must be obtained from every patient prior to any procedures being done specifically for the study. The final analysis populations will be described in the Statistical Analysis Plan (SAP),which will be signed off before database lock. For each patient screened, an electronic CRF (eCRF) will be completed, even if the patient drops out at any time point during the study. All eCRF information for the completed visits must be completed. After completion of the study, the data may be considered for reporting at a scientific conference and/or publication in scientific journals. LMU will be responsible for these activities and will collaborate with the investigators to determine how the manuscript is written and edited, the number and order of authors, the journal to which it will be submitted and other related issues. The results of the study will be published independent of the outcome - positive or negative — of the study
Principal Investigator : Beno Mbeya
Department Name :
Time frame: (2021-08-10) - (2023-10-10)
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