PanACEA DElpazolid Dose-finding and COmbination DEvelopment (DECODE)

NCT04550832 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: LCB01-0371-20-2-02PanACEA-DECODE-01
• Study Type: interventional
• Target: 76
• Locations: 2 countries
• Sites: 5

Brief Summary

This trial is to describe the safety, tolerability and exposure-toxicity relationship of Depazolid given over 16 weeks, in combination with standard-dose Bedaquiline, Delamanid and Moxifloxacin, compared to standard-dose Bedaquiline, Delamanid and Moxifloxacin alone

Conditions

Infections and Infestations; Pulmonary Tuberculosis

Keywords

drug-sensitive TB

Outcome Measures

Primary Outcomes (4)

• Safety Outcome : Proportion of Patients Experiencing Adverse Event

  Participants with ≥ 1 TEAE, by severity, related Adverse events: possibly, probably, or definitely related to study drugs

  week0 - week52

• Efficacy Outcome: Exposure-response Analysis With TTP (Time to Positive)_AUC0-24

  The efficacy of DZD was evaluated by measuring the change in mycobacterial load over time on treatment as quantified by TTP (Time to positive) in BD MGIT960® liquid culture described by non linear mixed effects methodology. A population PK model was developed using NONMEM version 7.4.1. DZD PK is well-described by a two-compartment model with first-order absorption, first-order elimination and a proportional residual error. The final model included allometric scaling based on FFM.

  Week 0 - Week 16

• Efficacy Outcome: Exposure-response Analysis With TTP (Time to Positive)_Cmax

  The efficacy of DZD was evaluated by measuring the change in mycobacterial load over time on treatment as quantified by TTP (Time to positive) in BD MGIT960® liquid culture described by non linear mixed effects methodology. A population PK model was developed using NONMEM version 7.4.1. DZD PK is well-described by a two-compartment model with first-order absorption, first-order elimination and a proportional residual error. The final model included allometric scaling based on FFM.

  Week 0 - Week 16

• Efficacy Outcome: Exposure-response Analysis With TTP (Time to Positive)_Cmin

  The efficacy of DZD was evaluated by measuring the change in mycobacterial load over time on treatment as quantified by TTP (Time to positive) in BD MGIT960® liquid culture described by non linear mixed effects methodology. A population PK model was developed using NONMEM version 7.4.1. DZD PK is well-described by a two-compartment model with first-order absorption, first-order elimination and a proportional residual error. The final model included allometric scaling based on FFM.

  Week 0 - Week 16

Secondary Outcomes (6)

• Efficacy Outcome: BD MGIT960® Liquid Media Culture Results

  Week 0 - Week 16

• Efficacy Outcome: Changes in Mycobacterial Load Over Time on Treatment as Quantified by Time to Positivity in BD MGIT960® Liquid Media

  Week 0 - Week 16

• Efficacy Outcome: Loewenstein-Jensen Solid Media Culture Results

  Week 0 - Week 16

• Efficacy Outcome: The Proportion Converted by Day Corresponding to End of Each Week

  Week 0 - Week 16

• Efficacy Outcome: Time to Culture Conversion

  Week 0 - Week 16

Study Arms (5)

Arm1(D0)

ACTIVE COMPARATOR

Participants receive the following medication for the duration of 16weeks together with food. * Delpazolid : Will not administered * Bedaquiline: will be dosed as per the licensed dose: 400 mg orally once daily for the first 14 days, then 200 mg three times a week. * Delamanid: will be dosed as per the licensed dose: 200 mg orally twice daily doses of 100 mg. * Moxifloxacin: will be dosed as per the licensed dose: 400 mg orally once daily

Drug: Bedaquiline, Delamanid, Moxifloxacin

Arm2(D400)

EXPERIMENTAL

Participants receive the following medication for the duration of 16weeks together with food. * Delpazolid : Will be dosed 400 mg orally once daily * Bedaquiline: will be dosed as per the licensed dose: 400 mg orally once daily for the first 14 days, then 200 mg three times a week. * Delamanid: will be dosed as per the licensed dose: 200 mg orally twice daily doses of 100 mg. * Moxifloxacin: will be dosed as per the licensed dose: 400 mg orally once daily

Drug: Delpazolid; Drug: Bedaquiline, Delamanid, Moxifloxacin

Arm3(D800-OD)

EXPERIMENTAL

Participants receive the following medication for the duration of 16weeks together with food. * Delpazolid : Will be dosed 800 mg orally once daily * Bedaquiline: will be dosed as per the licensed dose: 400 mg orally once daily for the first 14 days, then 200 mg three times a week. * Delamanid: will be dosed as per the licensed dose: 200 mg orally twice daily doses of 100 mg. * Moxifloxacin: will be dosed as per the licensed dose: 400 mg orally once daily

Drug: Delpazolid; Drug: Bedaquiline, Delamanid, Moxifloxacin

Arm4(D1200)

EXPERIMENTAL

Participants receive the following medication for the duration of 16weeks together with food. * Delpazolid : Will be dosed 1200 mg orally once daily * Bedaquiline: will be dosed as per the licensed dose: 400 mg orally once daily for the first 14 days, then 200 mg three times a week. * Delamanid: will be dosed as per the licensed dose: 200 mg orally twice daily doses of 100 mg. * Moxifloxacin: will be dosed as per the licensed dose: 400 mg orally once daily

Drug: Delpazolid; Drug: Bedaquiline, Delamanid, Moxifloxacin

Arm5(D800-BD)

EXPERIMENTAL

Participants receive the following medication for the duration of 16weeks together with food. * Delpazolid : Will be dosed 800 mg orally twice daily * Bedaquiline: will be dosed as per the licensed dose: 400 mg orally once daily for the first 14 days, then 200 mg three times a week. * Delamanid: will be dosed as per the licensed dose: 200 mg orally twice daily doses of 100 mg. * Moxifloxacin: will be dosed as per the licensed dose: 400 mg orally once daily

Drug: Delpazolid; Drug: Bedaquiline, Delamanid, Moxifloxacin

Interventions

Delpazolid DRUG

Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5.

Also known as: LCB01-0371

Arm2(D400); Arm3(D800-OD); Arm4(D1200); Arm5(D800-BD)

Bedaquiline, Delamanid, Moxifloxacin DRUG

These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5.

Also known as: BDM

Arm1(D0); Arm2(D400); Arm3(D800-OD); Arm4(D1200); Arm5(D800-BD)

Eligibility Criteria

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

You may qualify if:

• Provide written, informed consent prior to all trial-related procedures including HIV testing.
• Male or female, aged between 18 and 65 years, inclusive.
• Body weight between 40 and 90 kg, inclusive.
• Newly diagnosed, previously untreated, drug susceptible pulmonary TB: presence of MTB complex and rapid molecular tests result confirming susceptibility to RIF and INH such as GeneXpert and/or HAIN MTBDR plus.
• A chest X-ray (no older than 2 weeks) which, in the opinion of the Investigator, is consistent with TB.
• Sputum positive on microscopy from concentrated sputum for acid-fast bacilli on at least one sputum sample (at least 1+ on the IUATLD/WHO scale).
• The participant is willing to forgo consumption of foods high in tyramine for the period of taking study medication (See Appendix, section 20.2, page 92).
• The participant is either unable to conceive/father children AND/OR his/her partner is unable to conceive/father children AND/OR they will consent to be using effective methods of contraception when engaging in heterosexual intercourse, as defined below:
• a. Non-childbearing potential: i. Female participant/sexual partner of male participant: Bilateral oophorectomy, and/or hysterectomy or bilateral tubal ligation more than 12 months ago and/or has been postmenopausal with a history of no menses for at least 12 consecutive months ii. Male participant/sexual partner of female participant: Vasectomised or has had a bilateral orchidectomy minimally three months prior to screening iii. Male participants having a pregnant female partner or a male sexual partner: At least one barrier method has to be used in this case. b. Effective contraception methods: i. Female participants: Two methods, including methods that the patient's sexual partner(s) use. At least one must be a barrier method. Contraception must be practised for at least until 12 weeks after the last dose of DZD. ii. Male participants: Two methods, including methods that the patient's female sexual partner(s) use. At least one must be a barrier method. Effective contraception must be ensured for at least 16 weeks after the last dose of DZD.
• Note: hormone-based contraception alone may not be reliable when taking RIF during continuation phase; therefore, hormone-based contraceptives alone cannot be used by female participants/female partners of male participants to prevent pregnancy.

You may not qualify if:

• Circumstances that raise doubt about free, unconstrained consent to study participation (e.g. prisoner or mentally handicapped person)
• Poor general condition where delay in treatment cannot be tolerated or death within four months is likely.
• Poor social condition which would make it unlikely that the patient would be able to complete follow-up
• The patient is pregnant or breast-feeding.
• The patient is infected with HIV with a CD4 count \<220 cells/mm3. If \>220 cells/mm3, patients will be included only if any of the following is applicable:
• The patient is antiretroviral (ARV) naïve and able to postpone commencing HIV treatment for 2 months after the trial has started and then restrict regimens to those containing dolutegravir (see section 12.6.2 on ARVs) or The patient is ARV experienced (has been on ARV´s a minimum of 5 months) and able to switch to a dolutegravir-based regimen.
• The patient is treated with nucleosidic reverse transcriptase inhibitors (are permitted as concomitant medication).
• The patient is treated with protease inhibitors as part of antiretroviral treatment regimens, which will be stopped at least 3 days before the start of study treatment (WK01, day1) for a patient to be eligible.
• The patient is treated with Efavirenz as part of antiretroviral treatment regimens which would have to be stopped 14 days before the start of study treatment (WK00, Day 01) for a patient to be eligible.
• The patient has a known intolerance to any of the study drugs or concomitant disorders or conditions for which study drugs or standard TB treatment are contraindicated
• The patient has a history of, or current evidence of clinically relevant cardiovascular metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or any other condition that will influence treatment response, study adherence or survival in the judgement of the investigator, especially:
• Neuropathy, or significant psychiatric disorder like depression or schizophrenia; especially if treatment for those has ever been required or is anticipated to be required
• Clinically significant evidence of extra-pulmonary TB (e.g. miliary TB, TB meningitis, but not limited lymph node involvement)
• Serious lung conditions other than TB, or significant respiratory impairment in the discretion of the investigator
• Any diabetes mellitus

Sponsors & Collaborators

• LigaChem Biosciences, Inc.: lead
• Ludwig-Maximilians - University of Munich: collaborator
• Radboud University Medical Center: collaborator
• University of California, San Francisco: collaborator

Study Sites (5)

The Aurum Institute Tembisa Clinical Research Centre

Tembisa, Gauteng, 1632, South Africa

Location

Clinical HIV Research Unit (CHRU) University of the Witwatersrand

Johannesburg, 2092, South Africa

Location

Ifakara Health Institute

Bagamoyo, Tanzania

Location

National Institute for Medical Research (NIMR-MMRC)

Mbeya, Tanzania

Location

Ki'bongoto Infectious Disease Hospital (KIDH) Kilimanjaro Clinical Research Institute (KCRI)

Moshi, Tanzania

Location

Related Publications (2)

• Minja LT, van der Feltz I, Manyama C, Mpagama S, Mhimbira F, Norena I, Sebe M, Rassool M, Wallis RS, Ntinginya N, Liyoyo A, Mbeya B, Wagnerberger L, Zumba T, Peter DD, Makkan H, Sloan DJ, Brake LT, Schildkraut JA, Aarnoutse R, McHugh TD, Wildner L, Boeree MJ, Geiter L, Cho YL, Aldana BH, Phillips PPJ, Hoelscher M, Svensson EM, Heinrich N; PanACEA consortium. Delpazolid in combination with bedaquiline, delamanid, and moxifloxacin for pulmonary tuberculosis (PanACEA-DECODE-01): a prospective, randomised, open-label, phase 2b, dose-finding trial. Lancet Infect Dis. 2025 Nov;25(11):1219-1229. doi: 10.1016/S1473-3099(25)00289-0. Epub 2025 Jul 8.

  PMID: 40645198 RESULT

• Dierig A, Hoelscher M, Schultz S, Hoffmann L, Jarchow-MacDonald A, Svensson EM, Te Brake L, Aarnoutse R, Boeree M, McHugh TD, Wildner LM, Gong X, Phillips P, Minja LT, Ntinginya N, Mpagama S, Liyoyo A, Wallis RS, Sebe M, Mhimbira FA, Mbeya B, Rassool M, Geiter L, Cho YL, Heinrich N. 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 moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis. Trials. 2023 Jun 6;24(1):382. doi: 10.1186/s13063-023-07354-5.

  PMID: 37280643 DERIVED

MeSH Terms

Conditions

Infections; Tuberculosis, Pulmonary

Interventions

delpazolid; bedaquiline; OPC-67683; Moxifloxacin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Seonghye Cheon
• Organization: LigaChem Bioscience, Inc.

scheon@ligachembio.com

+82)02-6952-0689

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: September 1, 2020
• First Posted: September 16, 2020
• Study Start: October 28, 2021
• Primary Completion: January 4, 2023
• Study Completion: September 11, 2023
• Last Updated: September 16, 2025
• Results First Posted: October 28, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: PD will be provided 1 - 2 years after and up to 5 years after the publication of the article on the results of the trial
• Access Criteria: IPD access will be provided for analyses of related to the aims of research described in the protocol and for individual patient data meta-analyses to researchers who provide a methodologically sound proposal to yhlee@ligachembio.com

Locations

ZA (2); TA (3)