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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
Contacts et emplacements
Coordonnées de l'étude
- Nom: Morounfolu Olugbosi, MD
- Numéro de téléphone: +27 79 045 4917
- E-mail: morounfolu.olugbosi@tballiance.org
Sauvegarde des contacts de l'étude
- Nom: Leandra Lombard
- Numéro de téléphone: +27 83 30 76784
- E-mail: leandra.lombard@tballiance.org
Lieux d'étude
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East London, Afrique du Sud, 5201
- Pas encore de recrutement
- Synergy Biomed Research Institute
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Chercheur principal:
- Mookho Malahleha, MD
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Contact:
- Mookho Mallahleha, MD
- Numéro de téléphone: +27 34 722 2306
- E-mail: drmookho@sbri.org.za
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Durban
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Wentworth, Durban, Afrique du Sud, 4052
- Recrutement
- Durban International Clinical Research Site
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Contact:
- Umesh Lalloo, MD
- Numéro de téléphone: + 27 31 261 1093/5
- E-mail: lalloo@ecarefoundation.com
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Chercheur principal:
- Umesh Lalloo, MD
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Eastern Cape
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Port Elizabeth, Eastern Cape, Afrique du Sud, 6200
- Recrutement
- Isango Lethemba TB Research Unit
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Chercheur principal:
- Simone Faesen, MD
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Contact:
- Simone Faesen, MD
- Numéro de téléphone: +27 41 492 3195
- E-mail: SimFaesen@witshealth.co.za
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Gauteng
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Soshanguve, Gauteng, Afrique du Sud, 0152
- Recrutement
- Setshaba Research Centre
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Contact:
- Zinhie Zwane, MD
- Numéro de téléphone: +27 12 799 2422
- E-mail: Zzwane@setshabe.org.za
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Chercheur principal:
- Zinhle Zwane, MD
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Mowbray
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Cape Town, Mowbray, Afrique du Sud, 7700
- Recrutement
- University of Capetown Lung Institute
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Contact:
- Sherman PadayaChee, MD
- Numéro de téléphone: +27 21 404 7747
- E-mail: Sherman.Padayachee@uct.ac.za
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Chercheur principal:
- Sherman Padayachee, MD
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North West
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Rustenburg, North West, Afrique du Sud, 2999
- Recrutement
- The Aurum Institute, Rustenburg
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Contact:
- William Brumskine, MD
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Chercheur principal:
- William Brumskine, MD
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Contact:
- William Brumskine, MD
- Numéro de téléphone: +27 87 135 1575
- E-mail: wbrumskine@auruminstitute.org
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North West Provinvce
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Brits, North West Provinvce, Afrique du Sud, 0250
- Recrutement
- Madiberg Centre for Research
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Contact:
- Lindsey Faul, MD
- Numéro de téléphone: +27 12 252 1140
- E-mail: lfaul@madibengresearch.co.za
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Chercheur principal:
- Lindsey Faul, MD
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Northwest Province
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Klerksdorp, Northwest Province, Afrique du Sud, 2571
- Pas encore de recrutement
- Perinatal HIV Research Unit, Tshepong Hospital
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Contact:
- Ebrahim Variava, MD
- Numéro de téléphone: +27 18 406 3111
- E-mail: variave@phru.co.za
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Contact:
- Tumelo Moloantoa, MD
- Numéro de téléphone: +27 18 011 3800
- E-mail: moloantoat@phru.co.za
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Dar es Salaam, Tanzanie
- Pas encore de recrutement
- INUKA Africa
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Contact:
- Frederik Haraka, MD
- Numéro de téléphone: +255 22 270 0021/4
- E-mail: fharaka@inuka-africa.org
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Chercheur principal:
- Frederik Haraka, MD
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Mbeya, Tanzanie
- Pas encore de recrutement
- NIMR-Mbeya
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Contact:
- Christina Manyama, MD
- Numéro de téléphone: +255 25 250 3364
- E-mail: christina.manyama@nimr.or.tz
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Chercheur principal:
- Christina Manyama, MD
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Moshi, Tanzanie
- Pas encore de recrutement
- Kilimanjaro Clinical Research Institute(KCRI)
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Contact:
- Blandina Mmbaga, MD
- Numéro de téléphone: +255 27 275 4201
- E-mail: b.nmbaga@kcri.ac.tz
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Chercheur principal:
- Blandina Mmbaga, MD
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Mwanza, Tanzanie
- Pas encore de recrutement
- NIMRI-Mwanza
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Contact:
- Kidola Jeremiah, MD
- Numéro de téléphone: +255 28 250 3012
- E-mail: kiddola.jeremiah@nimri.or..tz
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Chercheur principal:
- Kidola Jeremiah, MD
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
La 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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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)
Autres noms:
one 200mg tablet taken once daily for 17 weeks
Autres noms:
one 600mg tablet taken once daily for 17 weeks
Autres noms:
|
|
Expérimental: 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)
Autres noms:
one 200mg tablet taken once daily for 17 weeks
Autres noms:
one 600mg tablet taken once daily for 17 weeks
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Incidence and characterization of treatment-emergent adverse events (TEAEs)
Délai: 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
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Time to stable sputum culture conversion (SSCC) to negative
Délai: 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
Délai: 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
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Directeur d'études: Morounfolu Olugbosi, TB Alliance
Publications et liens utiles
Liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Infections des voies respiratoires
- Infections
- Maladies des voies respiratoires
- Maladies pulmonaires
- Infections bactériennes à Gram positif
- Infections bactériennes
- Infections bactériennes et mycoses
- Infections à Actinomycétales
- Infections à mycobactéries
- Tuberculose
- Tuberculose pulmonaire
- Produits chimiques organiques
- Composés hétérocycliques, 1 anneau
- Composés hétérocycliques
- Azoles
- Acides, acyclique
- Acides carboxyliques
- Amides
- Acétamides
- Acétates
- Oxazolidinones
- Oxazoles
- Linézolide
- pré-ancré
- TBAJ-876
Autres numéros d'identification d'étude
- NC-010
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime 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/
Délai de partage IPD
Critères d'accès au partage IPD
Type d'informations de prise en charge du partage d'IPD
- PROTOCOLE D'ÉTUDE
- SÈVE
- CIF
Informations sur les médicaments et les dispositifs, documents d'étude
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