Sorfequiline-based 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 :
- 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
- 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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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:
- Screening period: Screening visit, up to 11 days prior to randomisation (Day 1)
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
- Follow-up Period: 52 weeks after end of treatment
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 2
Contatti e Sedi
Contatto studio
- Nome: Morounfolu Olugbosi, MD
- Numero di telefono: +27 79 045 4917
- Email: morounfolu.olugbosi@tballiance.org
Backup dei contatti dello studio
- Nome: Leandra Lombard
- Numero di telefono: +27 83 30 76784
- Email: leandra.lombard@tballiance.org
Luoghi di studio
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East London, Sud Africa, 5201
- Non ancora reclutamento
- Synergy Biomed Research Institute
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Investigatore principale:
- Mookho Malahleha, MD
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Contatto:
- Mookho Mallahleha, MD
- Numero di telefono: +27 34 722 2306
- Email: drmookho@sbri.org.za
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Durban
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Wentworth, Durban, Sud Africa, 4052
- Reclutamento
- Durban International Clinical Research Site
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Contatto:
- Umesh Lalloo, MD
- Numero di telefono: + 27 31 261 1093/5
- Email: lalloo@ecarefoundation.com
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Investigatore principale:
- Umesh Lalloo, MD
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Eastern Cape
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Port Elizabeth, Eastern Cape, Sud Africa, 6200
- Reclutamento
- Isango Lethemba TB Research Unit
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Investigatore principale:
- Simone Faesen, MD
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Contatto:
- Simone Faesen, MD
- Numero di telefono: +27 41 492 3195
- Email: SimFaesen@witshealth.co.za
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Gauteng
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Soshanguve, Gauteng, Sud Africa, 0152
- Reclutamento
- Setshaba Research Centre
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Contatto:
- Zinhie Zwane, MD
- Numero di telefono: +27 12 799 2422
- Email: Zzwane@setshabe.org.za
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Investigatore principale:
- Zinhle Zwane, MD
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Mowbray
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Cape Town, Mowbray, Sud Africa, 7700
- Reclutamento
- University of Capetown Lung Institute
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Contatto:
- Sherman PadayaChee, MD
- Numero di telefono: +27 21 404 7747
- Email: Sherman.Padayachee@uct.ac.za
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Investigatore principale:
- Sherman Padayachee, MD
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North West
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Rustenburg, North West, Sud Africa, 2999
- Reclutamento
- The Aurum Institute, Rustenburg
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Contatto:
- William Brumskine, MD
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Investigatore principale:
- William Brumskine, MD
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Contatto:
- William Brumskine, MD
- Numero di telefono: +27 87 135 1575
- Email: wbrumskine@auruminstitute.org
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North West Provinvce
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Brits, North West Provinvce, Sud Africa, 0250
- Reclutamento
- Madiberg Centre for Research
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Contatto:
- Lindsey Faul, MD
- Numero di telefono: +27 12 252 1140
- Email: lfaul@madibengresearch.co.za
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Investigatore principale:
- Lindsey Faul, MD
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Northwest Province
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Klerksdorp, Northwest Province, Sud Africa, 2571
- Non ancora reclutamento
- Perinatal HIV Research Unit, Tshepong Hospital
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Contatto:
- Ebrahim Variava, MD
- Numero di telefono: +27 18 406 3111
- Email: variave@phru.co.za
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Contatto:
- Tumelo Moloantoa, MD
- Numero di telefono: +27 18 011 3800
- Email: moloantoat@phru.co.za
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Dar es Salaam, Tanzania
- Non ancora reclutamento
- INUKA Africa
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Contatto:
- Frederik Haraka, MD
- Numero di telefono: +255 22 270 0021/4
- Email: fharaka@inuka-africa.org
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Investigatore principale:
- Frederik Haraka, MD
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Mbeya, Tanzania
- Non ancora reclutamento
- NIMR-Mbeya
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Contatto:
- Christina Manyama, MD
- Numero di telefono: +255 25 250 3364
- Email: christina.manyama@nimr.or.tz
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Investigatore principale:
- Christina Manyama, MD
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Moshi, Tanzania
- Non ancora reclutamento
- Kilimanjaro Clinical Research Institute(KCRI)
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Contatto:
- Blandina Mmbaga, MD
- Numero di telefono: +255 27 275 4201
- Email: b.nmbaga@kcri.ac.tz
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Investigatore principale:
- Blandina Mmbaga, MD
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Mwanza, Tanzania
- Non ancora reclutamento
- NIMRI-Mwanza
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Contatto:
- Kidola Jeremiah, MD
- Numero di telefono: +255 28 250 3012
- Email: kiddola.jeremiah@nimri.or..tz
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Investigatore principale:
- Kidola Jeremiah, MD
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
- Adulto
- Adulto più anziano
Accetta volontari sani
Descrizione
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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Triplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: 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 |
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)
Altri nomi:
one 200mg tablet taken once daily for 17 weeks
Altri nomi:
one 600mg tablet taken once daily for 17 weeks
Altri nomi:
|
|
Sperimentale: 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. |
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)
Altri nomi:
one 200mg tablet taken once daily for 17 weeks
Altri nomi:
one 600mg tablet taken once daily for 17 weeks
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Incidence and characterization of treatment-emergent adverse events (TEAEs)
Lasso di tempo: Through 17 weeks of treatment
|
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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Time to stable sputum culture conversion (SSCC) to negative
Lasso di tempo: Through 17 weeks of treatment
|
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
Lasso di tempo: 26 weeks after EOT; 52 weeks after EOT
|
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
|
Collaboratori e investigatori
Investigatori
- Direttore dello studio: Morounfolu Olugbosi, TB Alliance
Pubblicazioni e link utili
Collegamenti utili
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Infezioni delle vie respiratorie
- Infezioni
- Malattie delle vie respiratorie
- Malattie polmonari
- Infezioni batteriche Gram-positive
- Infezioni batteriche
- Infezioni batteriche e micosi
- Infezioni da actinomiceti
- Infezioni da micobatteri
- Tubercolosi
- Tubercolosi, Polmonare
- Prodotti chimici organici
- Composti eterociclici, 1-anello
- Composti eterociclici
- Azoli
- Acidi, aciclici
- Acidi carbossilici
- Amides
- Acetamidi
- Acetate
- Oxazolidinoni
- Oxazoli
- Linezolid
- premanide
- TBAJ-876
Altri numeri di identificazione dello studio
- NC-010
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
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/
Periodo di condivisione IPD
Criteri di accesso alla condivisione IPD
Tipo di informazioni di supporto alla condivisione IPD
- STUDIO_PROTOCOLLO
- LINFA
- ICF
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .