Phase 2 Trial of Sorfequiline Regimens in Adults With Newly Diagnosed Drug-sensitive Pulmonary TB

A Phase 2b, Randomised, Multi-center, Partially Blinded Trial Assessing the Safety and Efficacy of Regimens Containing Sorfequiline, Pretomanid and Linezolid in Adults With Newly Diagnosed, Drug-sensitive, Smear Positive Pulmonary Tuberculosis

The goal of this interventional trial is to evaluate the safety and efficacy of the loading dose regimen 200/100SPaL-4/13 weeks, and the 100SPaL -17 weeks regimen in adults with newly diagnosed, drug-sensitive, smear-positive pulmonary tuberculosis.

Participants (18-65 years) will be randomised 1:1, stratified by country and disease severity, to receive either :

1. a sorfequiline loading-dose regimen (200 mg daily for 4 weeks followed by 100 mg daily for 13 weeks) plus pretomanid 200 mg and linezolid 600 mg daily, or
2. sorfequiline 100 mg daily for 17 weeks plus pretomanid 200 mg and linezolid 600 mg daily. Study treatment is administered orally once daily with food.

The primary objective is to assess safety through 17 weeks of treatment, including treatment-emergent adverse events, ECG findings, vital signs, laboratory assessments, visual acuity, and peripheral neuropathy. Secondary objectives include assessments of efficacy (time to stable sputum culture conversion; favorable outcome and treatment failure/relapse at 26 and 52 weeks after end of treatment) and pharmacokinetics of trial drugs, with exploratory analyses including predictors of culture conversion, exposure-response relationships, and quality of life.

Study Overview

• Status: Not yet recruiting
• Conditions: Tuberculosis, Pulmonary
• Intervention / Treatment: Drug: sorfequiline; Drug: Pretomanid; Drug: Linezolid

Detailed Description

This is a phase 2, randomised, multi-center, partially blinded, clinical trial conducted in 2 treatment arms.

The trial will be performed at multiple centers in South Africa and Tanzania in at approximately 100 participants with DS-TB who meet all the inclusion criteria and none of the exclusion criteria, aged 18 to 65, inclusive. Participants will be randomised to one of the 2 sorfequiline, pretomanid and linezolid containing regimens and will be randomised in 1:1 ratio based on country and severity of disease (AFB 3+ and/or bilateral cavitation). T

The trial will consist of the following periods:

1. Screening period: Screening visit, up to 11 days prior to randomisation (Day 1)

2. Treatment Period: approximately 100 participants will be randomised equally to the 2 treatment arms below:

   • Sorfequiline 200 mg + pretomanid 200 mg + linezolid 600 mg for 4 weeks followed by sorfequiline 100 mg for 13 weeks
   • Sorfequiline 100 mg + pretomanid 200 mg + linezolid 600 mg for 17 week
3. Follow-up Period: 52 weeks after end of treatment

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Morounfolu Olugbosi, MD; Phone Number: +27 79 045 4917; Email: morounfolu.olugbosi@tballiance.org
• Study Contact Backup: Name: Leandra Lombard; Phone Number: +27 83 30 76784; Email: leandra.lombard@tballiance.org

Study Locations

• South Africa
  • East London, South Africa, 5201
    • Synergy Biomed Research Institute
    • Principal Investigator: Mookho Malahleha, MD
    • Contact: Mookho Mallahleha, MD; Phone Number: +27 34 722 2306; Email: drmookho@sbri.org.za
  • Bethelsdorp
    • Port Elizabeth, Bethelsdorp, South Africa, 6200
      • Isango Lethemba TB Research Unit
      • Principal Investigator: Simone Faesen, MD
      • Contact: Simone Faesen, MD; Phone Number: +27 41 492 3195; Email: SimFaesen@witshealth.co.za
  • Guateng
    • Pretoria, Guateng, South Africa, 0152
      • Setshaba Research Centre
      • Contact: Zinhie Zwane, MD; Phone Number: +27 12 799 2422; Email: Zzwane@setshabe.org.za
      • Principal Investigator: Zinhle Zwane, MD
  • Mowbray
    • Cape Town, Mowbray, South Africa, 7700
      • University of Capetown Lung Institute
      • Contact: Sherman PadayaChee, MD; Phone Number: +27 21 404 7747; Email: Sherman.Padayachee@uct.ac.za
      • Principal Investigator: Sherman Padayachee, MD
  • North West
    • Rustenburg, North West, South Africa, 2999
      • The Aurum Institute, Rustenburg
      • Contact: William Brumskine, MD
      • Principal Investigator: William Brumskine, MD
      • Contact: William Brumskine, MD; Phone Number: +27 87 135 1575; Email: wbrumskine@auruminstitute.org
  • North West Provinvce
    • Brits, North West Provinvce, South Africa, 0250
      • Madiberg Centre for Research
      • Contact: Lindsey Faul, MD; Phone Number: +27 12 252 1140; Email: lfaul@madibengresearch.co.za
      • Principal Investigator: Lindsey Faul, MD
  • Wentworth
    • Durban, Wentworth, South Africa, 4052
      • Durban International Clinical Research Site, Enhancing Care Foundation
      • Contact: Umesh Lalloo, MD; Phone Number: + 27 31 261 1093/5; Email: lalloo@ecarefoundation.com
      • Principal Investigator: Umesh Lalloo, MD
• Tanzania
  • Dar es Salaam, Tanzania
    • INUKA Africa
    • Contact: Frederik Haraka, MD; Phone Number: +255 22 270 0021/4; Email: fharaka@inuka-africa.org
    • Principal Investigator: Frederik Haraka, MD
  • Mbeya, Tanzania
    • Mbeya Referral Hospital
    • Contact: Christina Manyama, MD; Phone Number: +255 25 250 3364; Email: christina.manyama@nimr.or.tz
    • Principal Investigator: Christina Manyama, MD
  • Moshi, Tanzania
    • Kilimanjaro Clinical Research Instuute
    • Contact: Blandina Mmbaga, MD; Phone Number: +255 27 275 4201; Email: b.nmbaga@kcri.ac.tz
    • Principal Investigator: Blandina Mmbaga, MD
  • Mwanza, Tanzania
    • National Instittute for Medical Research
    • Contact: Kidola Jeremiah, MD; Phone Number: +255 28 250 3012; Email: kiddola.jeremiah@nimri.or..tz
    • Principal Investigator: Kidola Jeremiah, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• DS-TB as defined as sensitive to rifampicin and isoniazid by rapid sputum-based test AND either newly diagnosed for TB or have a history of being untreated for at least 3 years after cure from a previous episode of TB
• Of non-childbearing potential OR using effective birth control methods
• Body weight ≥ 35 k

Exclusion Criteria:

• Karnofsky score < 60 at screening
• Any evidence of extrapulmonary TB
• Cardiovascular or QT prolongation risk factors Pregnant or breast-feeding

• Laboratory abnormalities as defined in the protocol. • For participants living with HIV only:

  • CD4+ count<200 cells/μL.
  • WHO Clinical Stage 4 HIV disease
  • Participant does not agree to use DTG/TFV/3TC during study treatment if ARV therapy is indicated
  • If initiation of ARV therapy is indicated, participants who are known to be intolerant, non-responsive to DTG/TFV/3TC or have DTG/TFV/3TC as a contraindication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sorfequline 200/100-Pretomanid 200mg-Linezolid 600mg (Loading Dose); Regimen (17 weeks total): Weeks 1-4: Sorfequiline 200 mg + Pretomanid 200 mg + Linezolid 600 mg, once daily Weeks 5-17: Sorfequiline 100 mg + Pretomanid 200 mg + Linezolid 600 mg, once daily	Drug: sorfequiline; Two sorfequiline 100mg tablets taken once daily for 4 weeks then one sorfequiline taken once daily for 13 weeks OR one sorfequiline 100mg tablet taken once daily for 17 weeks (with one 100mg sorfequiline placebo tablet for the first 4 weeks); Other Names: S; TBAJ876; Drug: Pretomanid; one 200mg tablet taken once daily for 17 weeks; Other Names: P; PA-824; Dovprela; Drug: Linezolid; one 600mg tablet taken once daily for 17 weeks; Other Names: Zyvox; L; Linospan; Linosept; Lizolid
Experimental: Sorfequiline 100-Pretomanid 200mg-Linezolid 600mg (No Loading Dose); Regimen (17 weeks total): Weeks 1-17: Sorfequiline 100 mg + Pretomanid 200 mg + Linezolid 600 mg, once daily Includes sorfequiline placebo tablets during first 4weeks to maintain blinding vs the loading regimen.	Drug: sorfequiline; Two sorfequiline 100mg tablets taken once daily for 4 weeks then one sorfequiline taken once daily for 13 weeks OR one sorfequiline 100mg tablet taken once daily for 17 weeks (with one 100mg sorfequiline placebo tablet for the first 4 weeks); Other Names: S; TBAJ876; Drug: Pretomanid; one 200mg tablet taken once daily for 17 weeks; Other Names: P; PA-824; Dovprela; Drug: Linezolid; one 600mg tablet taken once daily for 17 weeks; Other Names: Zyvox; L; Linospan; Linosept; Lizolid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and characterization of treatment-emergent adverse events (TEAEs)	Includes severity, relationship to study drugs, seriousness, TEAEs leading to discontinuation, and TEAEs leading to death; plus safety monitoring endpoints (ECG, vital signs, clinical labs, visual acuity changes, peripheral neuropathy changes.	Through 17 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to stable sputum culture conversion (SSCC) to negative	SSCC defined as two negative cultures at least 7 days apart without an intervening MTB-positive result (protocol definition used for time-to-event analyses). Time Frame: Through 17 weeks of treatment	Through 17 weeks of treatment
Proportion with favorable outcome	Favorable outcome assessed post-treatment; protocol includes evaluation at 26 weeks and 52 weeks after end of treatment	26 weeks after EOT; 52 weeks after EOT

Collaborators and Investigators

• Sponsor: Global Alliance for TB Drug Development
• Investigators: Study Director: Morounfolu Olugbosi, TB Alliance

Publications and helpful links

General Publications

• Olugbosi M, Beumont M, Lombard L, Nedelman J, Timm J, Black T, Bruning-Barry R, Hickman D, Lombardi A, Betteridge M, Egizi E, Marcopulos L, Henderson J, Seidel S, Foraida S, Benhayoun M, Sun E. Protocol for a phase 2, partially blinded, randomized trial assessing the safety and efficacy of sorfequiline or bedaquiline in combination with pretomanid and linezolid in adult participants with newly diagnosed, drug-sensitive, smear-positive pulmonary tuberculosis (NC-009). Trials. 2026 Jan 6;27(1):102. doi: 10.1186/s13063-025-09413-5.

Helpful Links

• NC-009 Protocol Description

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 28, 2027
• Study Completion (Estimated): June 24, 2028

Study Registration Dates

• First Submitted: June 15, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 26, 2026

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: tuberculosis; pretomanid; linezolid; sorfequiline; drug sensitive tuberculosis
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Acids, Acyclic; Carboxylic Acids; Amides; Acetamides; Acetates; Oxazolidinones; Oxazoles; Linezolid; pretomanid; TBAJ-876
• Other Study ID Numbers: NC-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

There is an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The results of this trial may be published or presented at scientific meetings. If this is foreseen, the investigator agrees to submit all manuscripts or abstracts to TB Alliance before submission. This allows TB Alliance to protect proprietary information and to provide comments; such consent will not be withheld unreasonably . Finalized results are published following completion of the trial. At that time, requests for the IPD can be made to C-Path at https://c-path.org/tools-platforms/tb-pacts/

• IPD Sharing Time Frame: IPD will be available post trial completion
• IPD Sharing Access Criteria: Researchers will be able to access the IPD (datasets) and supporting information through C-path URL.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No