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 Results 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 (8)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs, TEAEs Related to Study Drug, TEAEs Leading to Study Discontinuation, TEAEs Leading to Death, and All Grade TEAEs Based on DAIDS Criteria

  An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant administered an investigational medicinal product or trial treatment and which does not necessarily have a causal relationship with this treatment. TEAEs are AEs with an onset date on or after the start of treatment. Serious AE are AEs that leads to death, is life threatening, requires or prolongs hospitalization, significant disability, congenital anomaly or birth defect, and other medically important serious advent. AEs were graded on a severity 3-point scale as follows: Mild: Discomfort noticed, but no disruption to daily activity.; Moderate: Discomfort sufficient to reduce or affect normal daily activity.;Severe: Inability to work or perform normal daily activity. As pre-specified in statistical analysis plan (SAP),Division of AIDS (DAIDS v2.1) criteria was used and AEs graded as follows:Grade 1-Mild;Grade 2-Moderate;Grade 3-Severe;Grade 4-Life Threatening;Grade 5-Death.

  From first dose of study drug up to end of follow up period (up to Week 52)

• Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities

  Laboratory assessments included clinical chemistry (Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Total Bilirubin, Calcium, Creatinine, estimated Glomerular Filtration Rate (eGFR), Glucose, Fasting and Non-Fasting, Cholesterol, Inorganic Phosphorus, Magnesium, Potassium, Sodium, Triglycerides and Uric Acid), hematology (Activated Partial Thromboplastin Time, Prothrombin Time, Partial Thromboplastin Time, International Normalized Ratio (INR), Absolute CD4+ Count, Absolute Lymphocytes, Absolute Neutrophil Count, Hemoglobin, Platelet Count, White Blood Cell), and urinalysis (Urine Glucose, Blood and Protein). As pre-specified in statistical analysis plan (SAP), Division of AIDS (DAIDS) criteria was used and abnormalities were graded as follows:Grade 1 - Mild; Grade 2 - Moderate; Grade 3 - Severe; Grade 4 - Life Threatening; Grade 5 - Death. Laboratory values with DAIDS Grade ≥3 were considered as potentially clinically relevant abnormalities and are reported here.

  Baseline up to end of follow up period (up to Week 52)

• Number of Participants With Potentially Clinically Relevant Abnormalities in the Vital Signs

  Vital signs measurements included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, body weight, and body temperature. Blood pressure (i.e., SBP, DBP) and heart rate were measured in the supine and sitting positions after the participant had been in each position for at least 3 minutes. The participants were categorized based on the clinically relevant vital sign values as per DAIDS criteria pre-specified in SAP. Each vital sign parameter was graded using the DAIDS criteria as follows: Grade 1 - Mild; Grade 2 - Moderate; Grade 3 - Severe; Grade 4 - Potentially Life Threatening; Grade 5 - Death. The categories with at least one participant with clinically significant value of any grade for vital signs are reported here.

  Baseline up to end of follow up period (up to Week 52)

• Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities

  3 ECGs were performed at baseline (Day -1) spaced 5 to 10 minutes apart, and 3 ECGs at all subsequent visits during the treatment and follow-up periods. The categories with at least one participant with clinically relevant ECG abnormalities are reported here.

  Baseline up to end of follow up period (up to Week 52)

• Number of Participants With an AE Reported as DAIDS Grade 3 or Higher

  An AE was defined as any untoward medical occurrence in a clinical trial participant administered a treatment that does not necessarily have a causal relationship with the treatment. All AEs were graded on a 5-point scale according to DAIDS Table for Grading the Severity of Adult and Pediatric AEs as follows: Grade 1 - Mild; Grade 2 - Moderate; Grade 3 - Severe; Grade 4 - Life Threatening; Grade 5 - Death.

  From first dose of study drug up to end of follow up period (up to approximately Week 52)

• Number of Participants With TEAEs Leading to Discontinuation of Treatment

  An AE was defined as any untoward medical occurrence in a clinical trial participant administered an investigational medicinal product or trial treatment and which does not necessarily have a causal relationship with this treatment. TEAEs are AEs with an onset date on or after the start of treatment.

  From first dose of the study drug up to end of follow up period (up to approximately Week 52)

• Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) in Mycobacteria Growth Indicator Tube® (MGIT) by End of Treatment (Week 17)

  A participant was classified as having achieved SCC if the participant achieved first 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis at least 1 week apart (±4 days) after his/her last sputum culture that was positive for growth, and did not have a positive sputum culture result in between, and by the end of the treatment. Efficacy was assessed by using the MGIT liquid culture system. 95% confidence interval (CI) was calculated using Clopper Pearson (exact) confidence interval model.

  Week 17

• Percentage of Participants Who Achieved SCC in MGIT by End of Treatment (Week 26)

  A participant was classified as having achieved SCC if the participant achieved first 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis at least 1 week apart (±4 days) after his/her last sputum culture that was positive for growth, and did not have a positive sputum culture result in between, and by the end of the treatment. Efficacy was assessed by using the MGIT liquid culture system. 95% CI is calculated using Clopper Pearson (exact) confidence interval model.

  Week 26

Secondary Outcomes (5)

• Percentage of Participants Who Achieved SCC in MGIT by the End of 8 Weeks of Treatment

  Week 8

• Time to Detection of MGIT Cultures

  Baseline up to Week 52

• Percentage of Participants Achieving Negative Sputum Lipoarabinomannan (LAM) by 8 Weeks of Treatment and by End of Treatment

  Week 8, and End of Treatment Period - Week 17 (for OPC-167832 arms) and Week 26 (for RHEZ arm)

• Percentage of Participants With Acquired Drug Resistance

  Baseline up to Week 52

• Time to Sputum Culture Conversion (SCC)

  From the first dose of the study up to the end of the follow-up period (up to Week 52)

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; Drug: Bedaquiline; Drug: 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; Drug: Bedaquiline; Drug: 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; Drug: Bedaquiline; Drug: 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; Drug: Rifampin; Drug: Isoniazid

Interventions

OPC-167832 30 mg DRUG

OPC-167832 (30 mg QD) for 17 weeks

Delamanid + Bedaquiline + OPC-167832 30 mg

RHEZ DRUG

RHEZ (RIFAFOUR single dose combination tablets) for 8 weeks

Also known as: RIFAFOUR

Rifampin, Isoniazid, Ethambutol, and Pyrazinamide (RHEZ)

Delamanid DRUG

Delamanid (300 mg QD) for 17 weeks

Delamanid + Bedaquiline + OPC-167832 10 mg; Delamanid + Bedaquiline + OPC-167832 30 mg; Delamanid + Bedaquiline + OPC-167832 90 mg

Bedaquiline DRUG

Bedaquiline (400 mg QD x 2 weeks, then 200 mg TIW) for 17 weeks

Delamanid + Bedaquiline + OPC-167832 10 mg; Delamanid + Bedaquiline + OPC-167832 30 mg; Delamanid + Bedaquiline + OPC-167832 90 mg

Rifampin DRUG

Rifampin tablets for 18 weeks

Rifampin, Isoniazid, Ethambutol, and Pyrazinamide (RHEZ)

Isoniazid DRUG

Isoniazid tablets for 18 weeks

Rifampin, Isoniazid, Ethambutol, and Pyrazinamide (RHEZ)

OPC-167832 10 mg DRUG

OPC-167832 (10 mg QD) for 17 weeks

Delamanid + Bedaquiline + OPC-167832 10 mg

OPC-167832 90 mg DRUG

OPC-167832 (90 mg QD) for 17 weeks

Delamanid + Bedaquiline + OPC-167832 90 mg

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 (2)

• Dawson R, Diacon AH, Variava E, Moloantoa T, Brumskine W, Ngwanto T, Zuma-Gwala N, Osman A, Rassool M, Bennet JA, Liu Y, Xu R, Li W, Takuva S, Hafkin J. Efficacy and safety of a 4-month quabodepistat, delamanid, and bedaquiline regimen for drug-susceptible pulmonary tuberculosis: a multicentre, open-label, randomised, proof-of-concept, non-inferiority, phase 2b/c trial. Lancet Infect Dis. 2026 May 29:S1473-3099(26)00143-X. doi: 10.1016/S1473-3099(26)00143-X. Online ahead of print.

  PMID: 42214407 DERIVED

• 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

Related Links

• Otsuka Clinical Trial Website:
• Otsuka Clinical Trial Transparency:

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

OPC-67683; bedaquiline; Rifampin; Isoniazid

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

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Clinical Transparency
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

smb_clinicaltranspa@otsuka-us.com

08446878522

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: August 12, 2026
• Results First Posted: August 12, 2026

Record last verified: 2026-07

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)