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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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 de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Morounfolu Olugbosi, MD
- Número de teléfono: +27 79 045 4917
- Correo electrónico: morounfolu.olugbosi@tballiance.org
Copia de seguridad de contactos de estudio
- Nombre: Leandra Lombard
- Número de teléfono: +27 83 30 76784
- Correo electrónico: leandra.lombard@tballiance.org
Ubicaciones de estudio
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East London, Sudáfrica, 5201
- Aún no reclutando
- Synergy Biomed Research Institute
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Investigador principal:
- Mookho Malahleha, MD
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Contacto:
- Mookho Mallahleha, MD
- Número de teléfono: +27 34 722 2306
- Correo electrónico: drmookho@sbri.org.za
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Durban
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Wentworth, Durban, Sudáfrica, 4052
- Reclutamiento
- Durban International Clinical Research Site
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Contacto:
- Umesh Lalloo, MD
- Número de teléfono: + 27 31 261 1093/5
- Correo electrónico: lalloo@ecarefoundation.com
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Investigador principal:
- Umesh Lalloo, MD
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Eastern Cape
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Port Elizabeth, Eastern Cape, Sudáfrica, 6200
- Reclutamiento
- Isango Lethemba TB Research Unit
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Investigador principal:
- Simone Faesen, MD
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Contacto:
- Simone Faesen, MD
- Número de teléfono: +27 41 492 3195
- Correo electrónico: SimFaesen@witshealth.co.za
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Gauteng
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Soshanguve, Gauteng, Sudáfrica, 0152
- Reclutamiento
- Setshaba Research Centre
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Contacto:
- Zinhie Zwane, MD
- Número de teléfono: +27 12 799 2422
- Correo electrónico: Zzwane@setshabe.org.za
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Investigador principal:
- Zinhle Zwane, MD
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Mowbray
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Cape Town, Mowbray, Sudáfrica, 7700
- Reclutamiento
- University of Capetown Lung Institute
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Contacto:
- Sherman PadayaChee, MD
- Número de teléfono: +27 21 404 7747
- Correo electrónico: Sherman.Padayachee@uct.ac.za
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Investigador principal:
- Sherman Padayachee, MD
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North West
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Rustenburg, North West, Sudáfrica, 2999
- Reclutamiento
- The Aurum Institute, Rustenburg
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Contacto:
- William Brumskine, MD
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Investigador principal:
- William Brumskine, MD
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Contacto:
- William Brumskine, MD
- Número de teléfono: +27 87 135 1575
- Correo electrónico: wbrumskine@auruminstitute.org
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North West Provinvce
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Brits, North West Provinvce, Sudáfrica, 0250
- Reclutamiento
- Madiberg Centre for Research
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Contacto:
- Lindsey Faul, MD
- Número de teléfono: +27 12 252 1140
- Correo electrónico: lfaul@madibengresearch.co.za
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Investigador principal:
- Lindsey Faul, MD
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Northwest Province
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Klerksdorp, Northwest Province, Sudáfrica, 2571
- Aún no reclutando
- Perinatal HIV Research Unit, Tshepong Hospital
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Contacto:
- Ebrahim Variava, MD
- Número de teléfono: +27 18 406 3111
- Correo electrónico: variave@phru.co.za
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Contacto:
- Tumelo Moloantoa, MD
- Número de teléfono: +27 18 011 3800
- Correo electrónico: moloantoat@phru.co.za
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Dar es Salaam, Tanzania
- Aún no reclutando
- INUKA Africa
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Contacto:
- Frederik Haraka, MD
- Número de teléfono: +255 22 270 0021/4
- Correo electrónico: fharaka@inuka-africa.org
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Investigador principal:
- Frederik Haraka, MD
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Mbeya, Tanzania
- Aún no reclutando
- NIMR-Mbeya
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Contacto:
- Christina Manyama, MD
- Número de teléfono: +255 25 250 3364
- Correo electrónico: christina.manyama@nimr.or.tz
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Investigador principal:
- Christina Manyama, MD
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Moshi, Tanzania
- Aún no reclutando
- Kilimanjaro Clinical Research Institute(KCRI)
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Contacto:
- Blandina Mmbaga, MD
- Número de teléfono: +255 27 275 4201
- Correo electrónico: b.nmbaga@kcri.ac.tz
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Investigador principal:
- Blandina Mmbaga, MD
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Mwanza, Tanzania
- Aún no reclutando
- NIMRI-Mwanza
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Contacto:
- Kidola Jeremiah, MD
- Número de teléfono: +255 28 250 3012
- Correo electrónico: kiddola.jeremiah@nimri.or..tz
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Investigador principal:
- Kidola Jeremiah, MD
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
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 de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
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 |
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)
Otros nombres:
one 200mg tablet taken once daily for 17 weeks
Otros nombres:
one 600mg tablet taken once daily for 17 weeks
Otros nombres:
|
|
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. |
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)
Otros nombres:
one 200mg tablet taken once daily for 17 weeks
Otros nombres:
one 600mg tablet taken once daily for 17 weeks
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Incidence and characterization of treatment-emergent adverse events (TEAEs)
Periodo de tiempo: Through 17 weeks of treatment
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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
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Time to stable sputum culture conversion (SSCC) to negative
Periodo de tiempo: 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
Periodo de tiempo: 26 weeks after EOT; 52 weeks after EOT
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Favorable outcome assessed post-treatment; protocol includes evaluation at 26 weeks and 52 weeks after end of treatment
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26 weeks after EOT; 52 weeks after EOT
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Morounfolu Olugbosi, TB Alliance
Publicaciones y enlaces útiles
Enlaces Útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Infecciones del Tracto Respiratorio
- Infecciones
- Enfermedades de las vías respiratorias
- Enfermedades pulmonares
- Infecciones por bacterias grampositivas
- Infecciones bacterianas
- Infecciones bacterianas y micosis
- Infecciones por Actinomycetales
- Infecciones por micobacterias
- Tuberculosis
- Tuberculosis Pulmonar
- Químicos orgánicos
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Azoles
- Ácidos, acíclico
- Ácidos carboxílicos
- Amidas
- Acetamidas
- Acetato
- Oxazolidinonas
- Oxazoles
- Linezolida
- pretomaní
- TBAJ-876
Otros números de identificación del estudio
- NC-010
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan 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/
Marco de tiempo para compartir IPD
Criterios de acceso compartido de IPD
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- CIF
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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