SIRTURO® Clinical Trials

ADULT PATIENTS

Study 1

Study Design

A placebo-controlled, double-blind, randomized trial (Study 1) was conducted in newly diagnosed patients with multi-drug resistant pulmonary Mycobacterium tuberculosis.

Patients were randomized to receive treatment with:

  • SIRTURO® (bedaquiline) and other drugs used to treat MDR-TB (SIRTURO® treatment group) (n=79); or
  • placebo plus other drugs used to treat MDR-TB (placebo treatment group) (n=81)

The other drugs used to treat MDR-TB consisted of a combination of 5 other antimycobacterial drugs:

  • ethionamide
  • kanamycin
  • pyrazinamide
  • ofloxacin
  • cycloserine/terizidone or available alternative

SIRTURO® was administered as 400 mg once daily for the first 2 weeks and as 200 mg 3 times per week for the following 22 weeks.

After the 24-week study drug (SIRTURO® or placebo) treatment phase, patients continued to receive their other drugs used to treat MDR-TB until a total treatment duration of 18 to 24 months was achieved, or at least 12 months after the first confirmed negative culture.

Sixty-seven patients randomized to SIRTURO® and 66 patients randomized to placebo had confirmed MDR-TB, based on susceptibility tests (taken prior to randomization) or medical history if no susceptibility results were available, and were included in the efficacy analyses.

Study Population

  • 63% Male
  • Median age 34 years
  • 35% Black
  • 15% HIV positive
  • Most patients had cavitation in one lung (62%)
  • Cavitation in both lungs was observed in 18% of patients

Results

Time to sputum culture conversion was defined as the interval in days between the first dose of study drug and the date of the first of 2 consecutive negative sputum cultures collected at least 25 days apart during treatment.

In this trial, the SIRTURO® treatment group had a decreased time to culture conversion and improved culture conversion rates compared to the placebo treatment group at Week 24.

  • Median time to culture conversion was 83 days for the SIRTURO® treatment group compared to 125 days for the placebo treatment group.
  • The table below shows the proportion of patients with sputum culture conversion after 24 weeks and 120 weeks of treatment with SIRTURO® or placebo in combination with other drugs used to treat MDR-TB.

Culture Conversion Status

Study 2

Study Design

Study 2 was a smaller placebo-controlled study designed similarly to Study 1, except that SIRTURO® or placebo was given for only 8 weeks instead of 24 weeks.

Patients were randomized to receive treatment with:

  • SIRTURO® and other drugs used to treat MDR-TB (SIRTURO® treatment group) (n=23); or
  • placebo and other drugs used to treat MDR-TB (placebo treatment group) (n=24)

Twenty-one patients randomized to the SIRTURO® treatment group and 23 patients randomized to the placebo treatment group had confirmed MDR-TB based on patients’ baseline Mycobacterium tuberculosis isolate obtained prior to randomization.

Results

At Week 8, compared to the placebo treatment group, the SIRTURO® treatment group had:

  • Decreased time to culture conversion
  • Improved culture conversion rates

At Weeks 8 and 24 respectively, the differences in culture conversion proportions were:

  • 38.9% (95% CI: [12.3%, 63.1%] and P value: 0.004)
  • 15.7% (95% CI: [-11.9%, 41.9%] and P value: 0.32)

Study 3

Study Design:

Study 3 was a Phase 2b, uncontrolled study to evaluate the safety, tolerability, and efficacy of SIRTURO® as part of an individualized MDR-TB treatment regimen in 233 patients with sputum smear positive (within 6 months prior to screening) pulmonary MDR-TB. Patients received SIRTURO® for 24 weeks in combination with antibacterial drugs. Upon completion of the 24 week treatment with SIRTURO®, all patients continued to receive their background regimen in accordance with national TB program (NTP) treatment guidelines. A final evaluation was conducted at Week 120. Treatment responses to SIRTURO® at week 120 were generally consistent with those from Study 1.

PEDIATRIC PATIENTS (12 TO LESS THAN 18 YEARS OF AGE)

The pediatric trial (NCT02354014) was designed as a single-arm, open-label, trial to evaluate the pharmacokinetics, safety and tolerability of SIRTURO® in combination with a background regimen in patients 12 to less than 18 years of age with confirmed or probable pulmonary MDR-TB infection. Fifteen patients ages 14 to less than 18 years old were enrolled in the study. The median age was 16 years, 80% were female, 53% were Black and 13% Asian. No patients 12 to less than 14 years of age were enrolled in the study. SIRTURO® was administered as 400 mg once daily for the first 2 weeks and 200 mg 3 times/week for the following 22 weeks.

In the subset of patients with culture positive pulmonary MDR-TB at baseline, treatment with SIRTURO® resulted in a culture conversion rate of 75.0% (6/8 patients) at Week 24.