Ultra-Short Course Bedaquiline, Clofazimine, Pyrazinamide and Delamanid Versus Standard Therapy for Drug-Susceptible Tuberculosis

NCT05556746 | Active Not Recruiting Phase 2 Results DMC

• 2 other identifiers: 2022p003075U01AI170426
• Study Type: interventional
• Target: 94
• Locations: 2 countries
• Sites: 2

Brief Summary

The PRESCIENT trial is a Phase IIc, open-label, randomized trial that compared a 12-week regimen of bedaquiline (BDQ), clofazimine (CFZ), pyrazinamide (PZA), and delamanid (DLM) with standard treatment for drug-susceptible pulmonary tuberculosis (TB). Eligible participants were randomized in a 1:1 ratio to BDQ, CFZ, PZA, and DLM (BCZD) or standard anti-TB therapy. Participants in the experimental arm with evidence of poor clinical response at the end of therapy were re-treated with standard TB therapy. The primary analysis is a superiority efficacy comparison of time to liquid culture conversion through 8 weeks in the experimental (BCZD) arm vs. the standard therapy arm. The other key secondary outcome is safety.

Conditions

Tuberculosis, Pulmonary; HIV

Keywords

Pulmonary Tuberculosis; Treatment Shortening; HIV; Drug-Susceptible Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Median Time to Stable Liquid Culture Conversion by Week 8

  Culture conversion is defined as the first of two negative sputum cultures, consecutive or not, without an intervening positive culture, and/or visits wherein the participant is unable to produce sputum and has no signs or symptoms of active tuberculosis (TB).

  Measured through Week 8

Secondary Outcomes (16)

• Cumulative Probability of Experiencing Any Grade 3 or Higher Adverse Event (AE)

  Measured at Week 60

• Cumulative Probability of Having a Favorable Composite Outcome

  Measured at Week 60

• Proportion Who Prematurely Discontinue Treatment

  Measured at Week 12 in Arm 1 and Week 26 in Arm 2

• Median Time to Stable Liquid Culture Conversion by Week 12

  Measured through Week 12

• Mean Change in Skin Coloration Since TB Treatment Started at Weeks 8, 12, 16, 26, 60, and 86

  Weeks 8, 12, 16, 26, 60, and 86

Study Arms (2)

Arm 1 BCZD

EXPERIMENTAL

BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.

Drug: Bedaquiline (BDQ); Drug: Clofazimine (CFZ); Drug: Pyrazinamide (PZA); Drug: Delamanid (DLM)

Arm 2 RHZE

ACTIVE COMPARATOR

RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.

Drug: Rifampicin (RIF); Drug: Isoniazid (INH); Drug: Ethambutol (EMB); Drug: Pyrazinamide (PZA)

Interventions

Bedaquiline (BDQ) DRUG

Daily therapy for 12 weeks

Arm 1 BCZD

Clofazimine (CFZ) DRUG

Daily therapy for 12 weeks

Arm 1 BCZD

Pyrazinamide (PZA) DRUG

Daily therapy for 12 weeks

Arm 1 BCZD

Delamanid (DLM) DRUG

Daily therapy for 12 weeks

Arm 1 BCZD

Rifampicin (RIF) DRUG

Daily therapy for 26 weeks

Arm 2 RHZE

Isoniazid (INH) DRUG

Daily therapy for 26 weeks

Arm 2 RHZE

Ethambutol (EMB) DRUG

Daily therapy for 8 weeks

Arm 2 RHZE

Eligibility Criteria

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

You may qualify if:

• Informed consent obtained and signed.
• Pulmonary TB diagnosed by Xpert MTB/RIF, Xpert MTB/RIF Ultra, Line Probe Assay (LPA), or mycobacterial culture.
• Sputum positive for acid fast bacilli (at least 1+ grade on the WHO scale).
• Newly diagnosed with TB and have a history of being untreated for at least 6 months after cure from a previous episode of TB.
• For participants living with HIV, CD4+ cell count ≥200 cells/mm3, obtained within 30 days prior to study entry. Enrollment of participants living with HIV was limited to no more than 20% of the total study population.
• For participants living with HIV, must be currently receiving or planning to initiate ART at or before study week 8.
• Laboratory values at study screening:
• Alanine aminotransferase (ALT) ≤3x the upper limit of normal (ULN)
• Total bilirubin ≤2.5 x ULN
• Creatinine ≤2 x ULN
• Potassium ≥3.5 mEq/L, ≤5.5 mEq/L
• Absolute neutrophil count (ANC) ≥650/mm3
• Hemoglobin ≥7.0g/dL
• Platelet count ≥50,000/mm3
• For females of reproductive potential, negative serum or urine pregnancy test within 5 days prior to entry and willingness to use effective contraception for the duration of the study. Female participants who are not of reproductive potential must have documentation of menopause, hysterectomy, or bilateral oophorectomy or bilateral tubal ligation. Acceptable forms of contraception include: condoms, intrauterine device or intrauterine system, cervical cap with spermicide, diaphragm with spermicide.

You may not qualify if:

• More than 5 days of treatment directed against active TB for the current TB episode preceding study entry.
• Current extrapulmonary TB (e.g. neurological, skeletal, abdominal, or nodal), not including pleural TB, in the opinion of the site investigator.
• Pregnant or breastfeeding.
• Weight \<30kg.
• Inability to take oral medications.
• Current or planned use of any drug known to severely prolong the QTc interval, including, but not limited to: amiodarone, amitriptyline, chloroquine, chlorpromazine, cisapride, disopyramide, erthyromycin, moxifloxacin, procainamide, quinidine, or sotalol.
• Current or planned use of one or more of the following HIV medications: HIV protease inhibitors, HIV non-nucleoside reverse transcriptase inhibitors, elvitegravir/cobicistat, or bictegravir.
• Current or past use of clofazimine, bedaquiline or delamanid.
• QTcF \>450ms for men or \>470 ms for women.
• Current or history of known personal or family long QT syndrome.
• Known allergy/sensitivity to components of study TB drugs or their formulation.
• A. Screening, baseline study, and Week 1 visit sputum cultures fail to grow M. tuberculosis.
• B. Resistance to RIF or INH is detected from baseline molecular or phenotypic testing results that become available after enrollment.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• University of Cape Town: collaborator
• University of Stellenbosch: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic: collaborator
• University of California, Los Angeles: collaborator
• Harvard School of Public Health (HSPH): collaborator

Study Sites (2)

GHESKIO

Port-au-Prince, Haiti

Location

University of Cape Town

Cape Town, South Africa

Location

Related Links

• The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

bedaquiline; Clofazimine; Pyrazinamide; OPC-67683; Rifampin; Isoniazid; Ethambutol

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)

Phenazines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Ethylenediamines; Diamines; Polyamines; Amines

Limitations and Caveats

Accrual was stopped early due to both low conditional power (0.54%) for the primary outcome and a trend towards higher unfavorable outcomes in Arm 1 (BCZD).

Results Point of Contact

• Title: Dr. Serena Koenig
• Organization: Brigham and Women's Hospital

skoenig@bwh.harvard.edu

617-413-4090

Study Officials

• Serena Koenig, MD, MPH

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Sean Wasserman, MBChB, PhD

  University of Cape Town

  PRINCIPAL INVESTIGATOR

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: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Participants were randomized in a 1:1 ratio to the experimental or standard groups.

Study Record Dates

• First Submitted: September 20, 2022
• First Posted: September 27, 2022
• Study Start: November 24, 2023
• Primary Completion: June 12, 2025
• Study Completion (Estimated): January 1, 2027
• Last Updated: August 5, 2026
• Results First Posted: August 5, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

HA (1); ZA (1)