Evaluation of SQ109, High-dose Rifampicin, and Moxifloxacin in Adults With Smear-positive Pulmonary TB in a MAMS Design
Medical Research Council
Klinikum of the University of Munich

      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.
    
Drug