RESIST-TB Webinar: FDA Perspective

On September 6, 2018, RESIST-TB presented a webinar on Adequate and Well – Controlled Studies in the TB Regimen Development: An FDA Perspective. Hosted by Dr. Carole Mitnick, this webinar featured the expertise of FDA mathematical statistician, Karen Higgins

This presentation outlined the trials necessary to determine the efficacy of new TB drugs and regimens, the design differences between a single drug and a high impact regimen, and the pathway to FDA approval. 

To view the slides from this webinar, please click here.

For more information about FDA Guidance on non-inferiority trials, please visit: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM202140.pdf

 

TREAT TB Clinical Trial Implementation Webinar

On July 10, 2018, TREAT TB hosted its first webinar in a series to address challenges with implementing clinical trials of new treatments for MDR-TB in high burden settings.

Challenges with MDR-TB Clinical Trial Implementation- Sponsor and Site Perspectives featured discussions on current trials, sponsor challenges, challenges in trial implementation, setting up a trial site, patient enrollment, and regulatory requirements. The presentations for each of these discussions can be found below.

For more information about future webinars in this series, please visit: http://www.treattb.org/capacitybuilding/

 

Presentation slides on MDR-TB Clinical Trials Landscape available here.

Presentation slides on Sponsor Challenges available here.

Presentation slides on Challenges in Trial Implementation available here.

Presentation slides on Setting up a Trial Site available here.

Presentation slides on Patient Recruitment, Enrollment, and Retention available here.

Presentation slides on Regulatory Requirements available here.

 

Results of DR-TB Working Group Surveys, 2017 and 2018

On June 7th, DR-TB Working Group Co-Chairs Dr. Robert Horsburgh, Chen-Yuen Chiang, and Arnaud Trebucq presented a webinar hosted by The Union to review the results of the 2017-2018 DR-TB WG Survey.

The DR-TB WG Survey results explored the global implementation of the 9-month TB regimen and the use of bedaquiline and delamanid for MDR-TB treatment. The discussion examined barriers to progress related to rollout of these regimens based on 2018 survey results in comparison to those from 2017.  

Presentation slides from the DR-TB WG Survey 2018 available here.

Combined Use of DLM and BDQ on MDR-TB

On April 5th, Dr. Cathy Hewison and Dr. Lorenzo Guglielmetti presented a webinar on the current evidence and practices for the combined use of delamanid and bedaquiline for the treatment of MDR-TB.

Today, more and more clinicians around the world are experienced in using DLM and BDQ as part of a longer MDR-TB regimens with good results. However, there is less experience in using delamanid and bedaquiline together in the same MDR-TB treatment regimen due to concerns about the common effects on the QT interval. This webinar covered the current clinical practice and results of use of MDR-TB regimens containing the DLM and BDQ combination from endTB, MSF and Europe, as well an overview of the latest publications and the ongoing studies and trials.

Presentation slides from Dr. Hewison available here.

Presentation slides from Dr. Guglielmetti available here.

 

Nix TB and ZeNix Trials

On Thursday, January 11, 2018 by Dr. Dan Everitt, Vice President and Senior Medical Officer at TB Alliance, presented on New XDR-TB Regimens containing Pretomanid.

Dr. Dan Everitt, MD, of the Global Alliance presented the results of an important study of a six-month treatment regimen for XDR-TB using bedaquiline, pretomanid and linezolid, the NiX-TB trial. In addition, the Alliance expects to launch the ZeNix trial in late 2017. This clinical trial, to optimize the use of linezolid with bedaquiline and pretomanid, is expected to be conducted across 10 trial sites in South Africa, Georgia, Belarus, and Russia. Study design and current status was presented on the Webinar.

Presentation slides from Dr. Everitt available here.



STREAM MDR-TB Clinical Trial: Results of comparison of 9-Month Treatment Regimen to 20-24 month regimen.

On Thursday, December 14th, 2017 Dr. I.D. Rusen, Director of Research and Development at the Union, gave a presentation on the STREAM MDR-TB Clinical Trial: Results of comparison of 9-Month Treatment Regimen to 20-24 month regimen.

Dr. I.D. Rusen, MD, of the MRC presented the preliminary results from Stage 1 of the STREAM randomized clinical trial. These results have been eagerly awaited and were first made public at the Union meeting in Guadalajara.

 No presentation slides available.



LAM as a Pharmacodynamic Biomarker and Drug Development Tool for TB

On June 22nd, 2017, Dr. Yongge Liu, Director of Diagnostics at Otsuka Novel Products, gave a presentation on LAM (Lipoarabinomannan) as a Pharmacodynamic Biomarker and Drug Development Tool for TB. 

Otsuka Pharmaceutical is developing an assay that can measure the concentration of LAM, which is showing promise as a biomarker of the load of viable tubercle bacilli in sputum. The assay shows potential for real-time evaluation of treatment response in clinical trials, and Otsuka is working with the Critical Path to TB Drug Regimens (CPTR) to seek qualification of this biomarker as a drug development tool by the FDA in the USA and as a drug development method by the EMA in the European Union. Yongge Liu, the Director of Diagnostics at Otsuka Novel Products, will discuss the development of this assay and the biomarker qualification process.

A copy of the presentation slides can be viewed here.



TB-PRACTECAL Trial

On May 4th, 2017, Dr. Bern-Thomas Nyang’wa, MD gave a presentation on the The Pragmatic Clinical Trial for More Effective Concise and Less Toxic MDR-TB Treatment Regimen (TB-PRACTECAL).

TB-PRACTECAL is a multi-center, open label, multi-arm, randomized, controlled phase II-III trial. TB-PRACTECAL, a Médecins Sans Frontières (MSF) sponsored clinical trial, aims to evaluate short treatment regimens that contain bedaquiline and pretomanid in combination with existing and re-purposed anti-TB drugs for the treatment of biologically confirmed pulmonary MDR-  and XDR-TB.  The trial’s first patient was randomized and started treatment on January 17, 2017. Additional information on the trial can be found at https://www.msf.org.uk/content/tb-practecal.

Presentation slides not available.



TB-CHAMP Trial

On Thursday, April 20th, 2017 Dr. Anneke Hesseling, MBChB, MSc, PhD, gave a presentation on the TB-CHAMP Trial. 

The TB-CHAMP Trial is a phase III cluster randomized, double blind, placebo-controlled, superiority multicenter trial that aims to evaluate the efficacy of levofloxacin versus placebo as preventative therapy against MDR-TB in child and adolescent household contacts.  The TB-CHAMP Trial expects to begin enrolling patients this year.

A copy of the presentation slides can be viewed here.



The PHOENIx MDR-TB Trial

On January 19th, 2017 Dr. Gavin Churchyard, MBBCh, MMED, FCP (SA), PhD gave a presentation entitled “Protecting MDR-TB and XDR-TB Affected Households: The PHOENIx MDR-TB Trial.”

The Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients (PHOENIx) Study, is a phase III trial in development by the ACTG and IMPAACT networks aiming to asses the efficacy of six months of daily delamanid versus six months of isoniazid preventive therapy in high-risk household contacts of adult pulmonary MDR-TB cases.

Presentation slides not available.



The V-QUIN MDR Trial

On Thursday, November 3rd, 2016 Dr. Greg Fox hosted a webinar on the V-QUIN MDR Trial.

The webinar provided an update on the trial design, start-up, study sites, target population, and anticipated timeline of the V-QUIN MDR Trial. The V-QUIN Trial is a randomized controlled trial that aims to evaluate six months of daily levofloxacin versus six months of placebo as preventative therapy among household contacts of patients with MDR-TB. At this time, the V-QUIN Trial is only enrolling adults aged 15 years and above, with the hopes of enrolling children and adolescents at a later stage.  The V-QUIN Trial is currently enrolling participants in Vietnam.

A copy of the presentation slides can be viewed here.



ACTG 5343 Study

On Tuesday, September 13th, 2016, Dr. Kelly Dooley, MD PhD, gave a presentation on the ACTG 5343 Study. 

The ACTG 5343 study, conducted in South Africa and Peru, is a trial of the safety, tolerability, and pharmacokinetics of bedaquiline and delamanid, alone and in combination, among participants taking multidrug treatment for drug-resistant pulmonary tuberculosis.

A copy of the presentation slides can be viewed here.



endTB Clinical Trial: Evaluating Newly approved Drugs for Multidrug-Resistant TB

On June 23rd, 2016 Dr. Carole Mitnick hosted a webinar entitled “endTB Clinical Trial: Evaluating Newly approved Drugs for Multidrug-Resistant TB.”

This webinar provided an update on the design, study start-up, study sites, and anticipated timeline of the endTB clinical trial, a Phase III trial, using Bayesian outcome-adapted randomization to examine 5 all-oral, 9-month regimens for MDR-TB. All regimens contain at least one of the newly approved anti-TB drugs, bedaquiline and delamanid. The trial is supported by UNITAID and will be implemented by MSF & PIH and their partners.

A copy of the presentation slides can be viewed  here.



Identification of Patients Who Could Benefit from Bedaquiline or Delamanid

On March 16th, 2016, Maryline Bonnet gave a presentation entitled “Identification of Patients Who Could Benefit from Bedaquiline or Delamanid.”

WHO recommends adding bedaquiline or delamanid when a multidrug-resistant tuberculosis (MDR-TB) regimen with four effective drugs cannot be designed and delamanid in patients with high risk of poor outcomes. Based on a retrospective cohort study of outcomes of treatment of MDR-TB patients in programmes in Uzbekistan, Georgia, Armenia, Swaziland and Kenya, we aimed to identify patients at risk of unfavourable outcomes who may benefit of the new drugs. Of 1433 patients, 48.5% had body mass index (BMI) below 18.5Kg/m2, 72.9% high bacillary load, 16.7% harboured strains resistant to two injectables, 2.9% to ofloxacin, and 3.0% had extensively DRTB (XDR-TB). XDR-TB; resistance to two injectables or ofloxacin; imprisonment in the past; 2nd line drugs treatment history low BMI and high bacillary load were independently associated with unfavourable outcomes. In our cohort, patients who may benefit of the new drugs represented up to two thirds of all MDR-TB patients.

Presentation slides not available.



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.