Clofazimine – Repurpose & Strategy
On January 29th, 2016 Novartis Pharma’s Roxana Drake, MD PhD gave a presentation entitled Clofazimine –Repurpose & Strategy.
Novartis study CLAM320b2202 is a 30 month multi-center, phase 2b/3 randomized, open label trial to evaluate the efficacy and safety of clofazimine in patients with multidrug-resistant pulmonary tuberculosis. Patients will be randomized into one of two treatment arms. The experimental arm being the administration of 200 mg of clofazimine once daily in addition to the background regimen for 18 weeks followed by 100 mg clofazimine one daily in addition to the background regimen for the remainder of the 24-month treatment period. The control arm will only receive the background regimen for the entire 24-month treatment period. Both arms will undergo a 6 month follow up period.
The primary end points are to evaluate the effect of clofazimine when administrated orally in addition to background regimen compared to background regimen alone in producing higher cure rates at month 30 based on liquid culture media results in mycobacterial grown indicator tube (MGIT). The study will also assess the drugs effect on time to sputum culture conversion at week 24 using liquid culture media, the proportion of patients achieving sputum culture conversion at week 2, time to positive signal of MTB growth in liquid culture media, the drugs safety and tolerability, and routine safety EKG parameters. This study also contains a substudy that will examine the pharmacokinetic and pharmacodynamic characteristics of clofazimine, determine systemic trough concentrations of antiretroviral drugs co-administered with clofazimine, and explore the relationship between clofazimine concentration estimated using dried-blood spot methodology and traditional bioanalytical methods. The substudy will also assess the relationship between clofazimine plasma concentrations versus ECG parameters on Day -1 and Day 127 to evaluate differences in study arms and analyze serial sputum colony count during first 24 weeks of treatment.
This study plans to enroll 380 patients in multiple TB treatment centers worldwide to yield 310 patients, both male and female ages 14 to 70 years with 155 patients per arm. Enrollment will start on March 31st 2016 and will end on March 28th 2018. The treatment period will conclude on July 30th 2020 and follow ups will conclude in December 2020.
Presentation slides not available.