PanACEA Sutezolid Dose-finding and Combination Evaluation

Summary

This study is an open-label, randomized, controlled, multi-center Phase IIB dose-finding trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response-relationship of different doses of sutezolid (STZ) in combination with bedaquiline, delamanid and moxifloxacin in adults with newly diagnosed, uncomplicated, smear positive and drug sensitive pulmonary tuberculosis. Participants will be randomized to one of five arms containing bedaquiline, delamanid and moxifloxacin with different doses of STZ (0mg, 600mg once daily (OD), 1200mg OD, 600 mg twice daily (BD), 800 mg BD). Study treatment duration will be three months, followed by a follow-up period of 2 weeks.

The primary objective is to identify the optimal dose of sutezolid to be used in subsequent studies that provides the best efficacy at acceptable safety of the drug by describing the safety, tolerability and exposure toxicity relationship of sutezolid (and its main metabolite) given over three months, in combination with standard-dose bedaquiline, delamanid and moxifloxacin, compared to standard-dose bedaquiline, delamanid and moxifloxacin alone.

Conditions

• Pulmonary Tuberculosis
• Other Specified Pulmonary Tuberculosis

Interventions

DRUG

Sutezolid

Sutezolid is not licensed yet. Current experience in humans up to Phase IIA. Dose according to randomization to dosing arms 2-5.

DRUG

Bedaquiline, Delamanid, Moxifloxacin

These three licensed drugs form the backbone of a new regimen to which sutezolid is added in arms 2-5.

DRUG

Midazolam oral solution

Midazolam will be administered as per probe drug use in a single dose of 2 mg at day -1 and day 14 to assess the potential of sutezolid for CYP 459 3A4 enzyme induction, as measured by its influence on the ratio of AUCs of the CYP 3A4 probe drug

Sponsors & Collaborators

• European and Developing Countries Clinical Trials Partnership (EDCTP)

  collaborator OTHER_GOV

• Sequella, Inc.

  collaborator INDUSTRY

• Radboud University Medical Center

  collaborator OTHER

• University of California, San Francisco

  collaborator OTHER

• German Federal Ministry of Education and Research

  collaborator OTHER_GOV

• Michael Hoelscher

  lead OTHER

Principal Investigators

• Michael Hoelscher, Prof. · University Hospital, LMU Munich, Division of Infectious Diseases and Tropical Medicine

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-05-06

Primary Completion

2022-09-30

Completion

2022-09-30

FDA Drug

Yes

Countries

• South Africa
• Tanzania

Study Locations