Safety and Efficacy Evaluation of 4-month Regimen of OPC-167832, Delamanid and Bedaquiline in Participants With Drug-Susceptible Pulmonary TB

NCT05221502 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 323-201-00006
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 6

Brief Summary

This trial will assess the safety and efficacy of OPC-167832 combined with delamanid and bedaquiline in participants with drug-susceptible tuberculosis (DS-TB) administered for 17 weeks compared to rifampin, isoniazid, ethambutol, pyrazinamide (RHEZ) administered for 26 weeks.

Conditions

Pulmonary TB

Outcome Measures

Primary Outcomes (5)

• Incidence of Treatment Emergent Adverse Events

  Incidence of TEAEs: all TEAEs, TEAEs by severity, TEAEs potentially causally related to the IMP or trial medication, TEAEs with an outcome of death or trial medication, Serious TEAEs, TEAEs leading to discontinuation of the IMP or trial medication

  Baseline to 12 months post randomization

• Incidence of potentially clinically significant changes of laboratory tests from baseline and abnormalities in the vital signs, physical examinations, electrocardiograms (ECGs) at each visit were assessed and at end of study.

  Incidence of potentially clinically significant changes from baseline and abnormalities in the parameters below, at each visit were assessed and at end of study: Lab Tests: Hematology, Clinical Chemistry, CD4 Count, Urinalysis Vital Signs: systolic and diastolic blood pressure (mmHg), heart rate (beats/min), respiratory rate (breaths/min), body temperature (C), weight (kg) and body mass index (kg/m2) Physical exam include examination of the abdomen; extremities; head, eyes, ears, nose (HEENT); neurological; skin and mucosae; thorax; urogenital; audiometry assessment and visual assessment. ECGs: ECG PR interval (msec) ECG QTc interval (msec) ECG arrhythmia

  Baseline to 12 months post randomization

• Number of participants with a grade 3 or higher AE

  The proportion of subjects with a grade 3 or higher AE

  Baseline to 12 months post randomization

• Number of all cause Treatment Discontinuation

  Rate of All Cause Treatment Discontinuation

  Baseline to 12 months post randomization

• Sputum culture conversion (SCC) in Mycobacteria Growth Indicator Tube® (MGIT)

  The proportion of subjects achieving sputum culture conversion (SCC) in Mycobacteria Growth Indicator Tube® (MGIT) (Sputum culture conversion occurs when a subject has the first of 2 visits of at least 1 week apart (±4 days) with sputum cultures negative and without a positive sputum culture result in between).

  Baseline to End of Treatment Period - Week 17 and Week 26

Secondary Outcomes (5)

• Proportion of participants who achieve SCC in MGIT by 8 weeks of treatment

  Baseline to Week 8

• Time to detection of MGIT cultures

  Baseline to 12 months post randomization

• Proportion of participants who convert sputum LAM to negative by 8 weeks of treatment and by end of treatment

  End of Treatment Period - Week 17 and Week 26

• Proportion of participants who develop drug resistance

  Baseline to 12 months post randomization

• Time to Sputum Culture Conversion (SCC) of each treatment group.

  Baseline to 12 months post randomization

Other Outcomes (5)

• Assess the positron emission tomography/computerized axial tomography (PET/CT) imaging response over the course of treatment

  Baseline to Week 26

• Evaluate the ribosomal ribonucleic acid synthesis ratio (RS ratio) decline in sputum

  Baseline to 12 months post randomization

• Assess whole blood transcriptomic signatures previously associated with TB cure from serum

  Screening to 12 months post randomization

Study Arms (4)

Delamanid + Bedaquiline + OPC-167832 10 mg

EXPERIMENTAL

Participants will receive a combination regimen of delamanid, 300 mg, oral tablets, once daily (QD), bedaquiline, 400 mg, oral tablets, QD for 2 weeks, then 200 mg, thrice weekly (TIW) and OPC-167832, 10 mg, oral tablets, QD for a total of 17 weeks.

Drug: Delamanid + Bedaquiline + OPC-167832 10 mg

Delamanid + Bedaquiline + OPC-167832 30 mg

EXPERIMENTAL

Participants will receive a combination regimen of delamanid, 300 mg, oral tablets, QD, bedaquiline, 400 mg, oral tablets, QD for 2 weeks, then 200 mg, TIW and OPC-167832, 30 mg, oral tablets, QD for a total of 17 weeks.

Drug: Delamanid + Bedaquiline + OPC-167832 30 mg

Delamanid + Bedaquiline + OPC-167832 90 mg

EXPERIMENTAL

Participants will receive a combination regimen of delamanid, 300 mg, oral tablets, QD, bedaquiline, 400 mg, oral tablets, QD for 2 weeks, then 200 mg, TIW and OPC-167832, 90 mg, oral tablets, QD for a total of 17 weeks.

Drug: Delamanid + Bedaquiline + OPC-167832 90 mg

Rifampin, Isoniazid, Ethambutol, and Pyrazinamide (RHEZ)

ACTIVE COMPARATOR

Participants will receive RHEZ, orally, QD for 8 weeks followed by 18 weeks of rifampin and isoniazid for a total of 26 weeks.

Drug: RHEZ

Interventions

Delamanid + Bedaquiline + OPC-167832 10 mg DRUG

Delamanid (300 mg QD) + Bedaquiline (400 mg QD x 2 weeks, then 200 mg TIW) + OPC-167832 (10 mg QD) for 17 weeks

Delamanid + Bedaquiline + OPC-167832 10 mg

Delamanid + Bedaquiline + OPC-167832 30 mg DRUG

Delamanid (300 mg QD\] + Bedaquiline (400 mg QD x 2 weeks, then 200 mg TIW) + OPC-167832 (30 mg QD) for 17 weeks

Delamanid + Bedaquiline + OPC-167832 30 mg

Delamanid + Bedaquiline + OPC-167832 90 mg DRUG

Delamanid (300 mg QD) + Bedaquiline (400 mg QD x 2 weeks, then 200 mg TIW) + OPC-167832 (90 mg QD) for 17 weeks

Delamanid + Bedaquiline + OPC-167832 90 mg

RHEZ DRUG

RHEZ for 8 weeks followed by 18 weeks of rifampin and isoniazid (for a total of 26 weeks)

Rifampin, Isoniazid, Ethambutol, and Pyrazinamide (RHEZ)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written, informed consent prior to initiation of any trial-related procedures or treatments, and able, in the opinion of the investigator, to comply with all the requirements of the trial.
• Male or female participants between 18 and 65 years of age (inclusive) at the screening visit.
• Body weight ≥ 35.0 kg at the screening visit.
• Newly diagnosed, rifampin and isoniazid susceptible (on the screening sample) pulmonary TB.
• Able to spontaneously produce sputum.
• Females of childbearing potential (FOCBP) must agree to use 2 different approved methods of birth control or remain abstinent throughout their participation in the trial and for 12 weeks after the last dose of IMP or dose of RHEZ.
• Male participants must agree to use 2 different approved methods of birth control or remain abstinent throughout their participation in the trial and for 12 weeks after the last dose of IMP or RHEZ.

You may not qualify if:

• Participants are known or suspected of having resistance to rifampin, isoniazid, ethambutol, pyrazinamide, DLM, or BDQ either confirmed by the laboratory, or based on epidemiological history, at screening.
• Evidence of clinically significant metabolic (for example, including ongoing or current hypokalemia \[ie, potassium \<3.5 mEq/dL at screening\]), gastrointestinal, neurological, psychiatric, endocrine or liver (eg, hepatitis B and C) disease; malignancy; or other abnormalities (other than the indication being studied).
• History of, or current, clinically relevant cardiovascular disorder such as heart failure, coronary heart disease, uncontrolled hypertension, arrhythmia or symptom strongly suggestive of such a problem (for example, syncope or palpitations), tachyarrhythmia or status after myocardial infarction.
• Known bleeding disorders or family history of bleeding disorders.
• Any diseases or conditions in which the use of DLM, BDQ, OPC 167832, rifampin, isoniazid, pyrazinamide, or ethambutol is contraindicated.
• Any prior treatment for M tuberculosis within the past 2 years.
• Any treatment with a drug active against M tuberculosis (eg, quinolones) within the 3 months prior to screening.
• Clinical evidence of severe extrapulmonary TB (eg, miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis).
• Evidence of pulmonary silicosis, lung fibrosis, or other lung condition considered as severe by the investigator (other than TB). In particular, any underlying condition that could interfere with the assessment of x-ray images, sputum collection, or interpretation of sputum findings, or otherwise compromise the subject's participation in the trial.
• Any renal impairment characterized by creatinine clearance/estimated glomerular filtration rate (eGFR) of \< 60 mL/min/1.73 m2, or hepatic impairment characterized by alanine transaminase or aspartate transaminase \> 2.0 × upper limit of normal of the clinical laboratory reference range or bilirubin \> 2.0 × upper limit of normal of the clinical laboratory reference range, at screening.
• Screening glucose (nonfasting) ≥ 200 mg/dL or glycosylated hemoglobin (HbA1c) ≥ 6.5%.
• QTcF \> 450 msec in male participants (\> 470 msec in female participants), atrioventricular block II or III, bi-fasicular block, at screening or current or history of clinically significant ventricular arrhythmias. Other ECG abnormalities, if considered clinically significant by the investigator.
• Participants receiving any of the prohibited medications (see Section 6.5.1) within the specified periods or who would be likely to require prohibited concomitant therapy during the trial.
• Female participants who are breast-feeding or who have a positive pregnancy test result prior to receiving the first dose of IMP or RHEZ on Day 1.
• Current history of significant drug and/or alcohol abuse that is likely to result in poor adherence to trial requirements or that would pose a risk to the participant's well-being during the course of the trial.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (6)

Aurum Institute - Tembisa Clinical Research Centre

Tembisa, Gauteng, 1632, South Africa

Location

TASK Applied Science, Brooklyn Chest Hospital Premises

Cape Town, 7100, South Africa

Location

University of CapeTown Lung Center Institute

Cape Town, 7700, South Africa

Location

Themba Lethu Clinic Clinical HIV Research Unit (CHRU)

Johannesburg, 2092, South Africa

Location

Perinatal HIV Research Unit Tshepong Hospital Complex

Klerksdorp, 2574, South Africa

Location

Setshaba Research Center

Pretoria, 0152, South Africa

Location

Related Publications (1)

• Dawson R, Diacon AH, Takuva S, Liu Y, Zheng B, Karwe V, Hafkin J. Quabodepistat in combination with delamanid and bedaquiline in participants with drug-susceptible pulmonary tuberculosis: protocol for a multicenter, phase 2b/c, open-label, randomized, dose-finding trial to evaluate safety and efficacy. Trials. 2024 Jan 19;25(1):70. doi: 10.1186/s13063-024-07912-5.

  PMID: 38243296 DERIVED

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

OPC-67683; bedaquiline

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: February 3, 2022
• Study Start: April 12, 2022
• Primary Completion: April 8, 2024
• Study Completion: May 19, 2024
• Last Updated: April 10, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Locations

ZA (6)