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.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 2
Kontakte und Standorte
Studienkontakt
- Name: Morounfolu Olugbosi, MD
- Telefonnummer: +27 79 045 4917
- E-Mail: morounfolu.olugbosi@tballiance.org
Studieren Sie die Kontaktsicherung
- Name: Leandra Lombard
- Telefonnummer: +27 83 30 76784
- E-Mail: leandra.lombard@tballiance.org
Studienorte
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East London, Südafrika, 5201
- Noch keine Rekrutierung
- Synergy Biomed Research Institute
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Hauptermittler:
- Mookho Malahleha, MD
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Kontakt:
- Mookho Mallahleha, MD
- Telefonnummer: +27 34 722 2306
- E-Mail: drmookho@sbri.org.za
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Durban
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Wentworth, Durban, Südafrika, 4052
- Rekrutierung
- Durban International Clinical Research Site
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Kontakt:
- Umesh Lalloo, MD
- Telefonnummer: + 27 31 261 1093/5
- E-Mail: lalloo@ecarefoundation.com
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Hauptermittler:
- Umesh Lalloo, MD
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Eastern Cape
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Port Elizabeth, Eastern Cape, Südafrika, 6200
- Rekrutierung
- Isango Lethemba TB Research Unit
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Hauptermittler:
- Simone Faesen, MD
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Kontakt:
- Simone Faesen, MD
- Telefonnummer: +27 41 492 3195
- E-Mail: SimFaesen@witshealth.co.za
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Gauteng
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Soshanguve, Gauteng, Südafrika, 0152
- Rekrutierung
- Setshaba Research Centre
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Kontakt:
- Zinhie Zwane, MD
- Telefonnummer: +27 12 799 2422
- E-Mail: Zzwane@setshabe.org.za
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Hauptermittler:
- Zinhle Zwane, MD
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Mowbray
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Cape Town, Mowbray, Südafrika, 7700
- Rekrutierung
- University of Capetown Lung Institute
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Kontakt:
- Sherman PadayaChee, MD
- Telefonnummer: +27 21 404 7747
- E-Mail: Sherman.Padayachee@uct.ac.za
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Hauptermittler:
- Sherman Padayachee, MD
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North West
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Rustenburg, North West, Südafrika, 2999
- Rekrutierung
- The Aurum Institute, Rustenburg
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Kontakt:
- William Brumskine, MD
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Hauptermittler:
- William Brumskine, MD
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Kontakt:
- William Brumskine, MD
- Telefonnummer: +27 87 135 1575
- E-Mail: wbrumskine@auruminstitute.org
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North West Provinvce
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Brits, North West Provinvce, Südafrika, 0250
- Rekrutierung
- Madiberg Centre for Research
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Kontakt:
- Lindsey Faul, MD
- Telefonnummer: +27 12 252 1140
- E-Mail: lfaul@madibengresearch.co.za
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Hauptermittler:
- Lindsey Faul, MD
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Northwest Province
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Klerksdorp, Northwest Province, Südafrika, 2571
- Noch keine Rekrutierung
- Perinatal HIV Research Unit, Tshepong Hospital
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Kontakt:
- Ebrahim Variava, MD
- Telefonnummer: +27 18 406 3111
- E-Mail: variave@phru.co.za
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Kontakt:
- Tumelo Moloantoa, MD
- Telefonnummer: +27 18 011 3800
- E-Mail: moloantoat@phru.co.za
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Dar es Salaam, Tansania
- Noch keine Rekrutierung
- INUKA Africa
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Kontakt:
- Frederik Haraka, MD
- Telefonnummer: +255 22 270 0021/4
- E-Mail: fharaka@inuka-africa.org
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Hauptermittler:
- Frederik Haraka, MD
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Mbeya, Tansania
- Noch keine Rekrutierung
- NIMR-Mbeya
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Kontakt:
- Christina Manyama, MD
- Telefonnummer: +255 25 250 3364
- E-Mail: christina.manyama@nimr.or.tz
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Hauptermittler:
- Christina Manyama, MD
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Moshi, Tansania
- Noch keine Rekrutierung
- Kilimanjaro Clinical Research Institute(KCRI)
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Kontakt:
- Blandina Mmbaga, MD
- Telefonnummer: +255 27 275 4201
- E-Mail: b.nmbaga@kcri.ac.tz
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Hauptermittler:
- Blandina Mmbaga, MD
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Mwanza, Tansania
- Noch keine Rekrutierung
- NIMRI-Mwanza
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Kontakt:
- Kidola Jeremiah, MD
- Telefonnummer: +255 28 250 3012
- E-Mail: kiddola.jeremiah@nimri.or..tz
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Hauptermittler:
- Kidola Jeremiah, MD
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Beschreibung
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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Verdreifachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
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)
Andere Namen:
one 200mg tablet taken once daily for 17 weeks
Andere Namen:
one 600mg tablet taken once daily for 17 weeks
Andere Namen:
|
|
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)
Andere Namen:
one 200mg tablet taken once daily for 17 weeks
Andere Namen:
one 600mg tablet taken once daily for 17 weeks
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Incidence and characterization of treatment-emergent adverse events (TEAEs)
Zeitfenster: 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
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Time to stable sputum culture conversion (SSCC) to negative
Zeitfenster: 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
Zeitfenster: 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
|
Mitarbeiter und Ermittler
Ermittler
- Studienleiter: Morounfolu Olugbosi, TB Alliance
Publikationen und hilfreiche Links
Nützliche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Infektionen der Atemwege
- Infektionen
- Erkrankungen der Atemwege
- Lungenkrankheit
- Grampositive bakterielle Infektionen
- Bakterielle Infektionen
- Bakterielle Infektionen und Mykosen
- Actinomycetales-Infektionen
- Mycobacterium-Infektionen
- Tuberkulose
- Tuberkulose, Lungen
- Organische Chemikalien
- Heterocyclische Verbindungen, 1-Ring
- Heterocyclische Verbindungen
- Azolen
- Säuren, acyclisch
- Carboxylsäuren
- Amides
- Acetamides
- Acetate
- Oxazolidinone
- Oxazoles
- Linezolid
- prostomanid
- TBAJ-876
Andere Studien-ID-Nummern
- NC-010
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
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-Zeitrahmen
IPD-Sharing-Zugriffskriterien
Art der unterstützenden IPD-Freigabeinformationen
- STUDIENPROTOKOLL
- SAFT
- ICF
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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