Evaluation of SQ109, High-dose Rifampicin, and Moxifloxacin in Adults With Smear-positive Pulmonary TB in a MAMS Design

Summary

This study is a multiple-arm, multiple-stage (MAMS), phase 2, open label, randomized, controlled clinical trial that will compare the efficacy and safety of four experimental four drug regimens with a standard control regimen in patients with smear positive, pulmonary tuberculosis (TB). Patients will be randomly allocated to the control or one of the four experimental regimens in the ratio 2:1:1:1:1. Experimental regimens will be given for 12 weeks. Thereafter, participants in the experimental arms will receive continuation phase treatment for 14 weeks containing standard-dose rifampicin and isoniazid. All participants will receive 25 mg of vitamin B6 (pyridoxine) with every dose of INH to prevent INH-related neuropathy. Interim analyses will be conducted during the trial for efficacy, with the aim of identifying experimental arms that perform below a pre-specified efficacy threshold; these arms will then be stopped from further recruitment.

Following the first scheduled interim analysis on March 3rd, the Trial Steering Committee (TSC) followed a recommendation of the independent data monitoring committee (IDMC) and has stopped the enrolment into two of the arms in the MAMS-TB trial: HRZQ and HR20ZQ, based on these arms not meeting the pre-specified gain in efficacy over control. Importantly, there was no safety concern that prompted stopping recruitment to these arms. They recommended that recruitment to arm 2 (HRZQ) and 3 (HR20ZQ) be terminated as there was insufficient evidence that these regimens could shorten treatment. Importantly, there was no evidence that either arm was inferior to standard treatment (the control arm) with regards to efficacy. There was, however, sufficient evidence that the other intervention arms HR35ZE and HR20ZM could shorten treatment to continue enrolling patients.

Conditions

• Tuberculosis, Pulmonary

Interventions

DRUG

SQ109

SQ109 300 mg

DRUG

Rifampicin

Rifampicin 10 to 35 mg/kg

DRUG

Moxifloxacin

Moxifloxacin 400mg

DRUG

isoniazid

isoniazid 75 mg

DRUG

pyrazinamide

pyrazinamide 400 mg

DRUG

ethambutol

ethambutol 275 mg

DIETARY_SUPPLEMENT

pyridoxine

pyridoxine 25 mg

Sponsors & Collaborators

• Sequella, Inc.

  collaborator INDUSTRY

• European and Developing Countries Clinical Trials Partnership (EDCTP)

  collaborator OTHER_GOV

• German Federal Ministry of Education and Research

  collaborator OTHER_GOV

• Medical Research Council

  collaborator OTHER_GOV

• Radboud University Medical Center

  collaborator OTHER

• Michael Hoelscher

  lead OTHER

Principal Investigators

• Michael Hoelscher, MD · Klinikum of the University of Munich

• Martin Boeree, MD · Radboud University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-04-30

Primary Completion

2014-09-30

Completion

2015-03-31

Countries

• South Africa
• Tanzania

Study Locations