Efficacy and Tolerability of Bedaquiline, Delamanid, Levofloxacin, Linezolid, and Clofazimine to Treat MDR-TB

Summary

Multidrug-resistant tuberculosis (MDR-TB) is tuberculosis (TB) that is resistant to at least isoniazid and rifampicin, the two most important anti-TB drugs. It occurs in 3.6% of newly diagnosed TB patients in the world and 17% of patients who have been previously treated. In 2017, approximately 600,000 people were estimated to have acquired MDR-TB. However, only 25% of persons with MDR-TB were diagnosed and started on treatment, reflecting inadequate diagnostic capacity and lack of TB treatment capacity.

In this multicenter, randomized, partially blinded, four-arm, phase 2 study, the investigators will examine the efficacy and safety of an all-oral regimen of bedaquiline, delamanid, levofloxacin, linezolid, and clofazimine given for 16, 24, 32 or 40 weeks

Conditions

• Tuberculosis, Multidrug-Resistant

Interventions

DRUG

Delamanid

Frequency: daily Route of administration: oral Delamanid is a medication used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, for active multidrug-resistant tuberculosis. It is taken by mouth.

DRUG

Levofloxacin

Frequency: daily Route of administration: oral Levofloxacin is an antibiotic used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, urinary tract infections, chronic prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis.

DRUG

Bedaquiline

Frequency: daily Route of administration: oral Bedaquiline is indicated for use as part of an appropriate combination regimen for pulmonary multidrug-resistant tuberculosis (MDR-TB) in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability.

DRUG

Clofazimine

Frequency: daily Route of administration: oral Clofazimine has shown activity against multidrug-resistant tuberculosis (MDR-TB) and is now recommended by the World Health Organization (WHO) to treat drug resistant tuberculosis as a "Group B" drug. It is thought that clofazimine acts by inhibiting the formation of matrixes within the DNA and thus delaying the growth of the bacterium. Clofazimine first received FDA approval in 1986, although its use in the treatment of MDR-TB has not been approved by any stringent regulatory authorities and it is therefore used "off-label" for this function.

DRUG

Linezolid

Frequency: daily Route of administration: oral Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics.

Sponsors & Collaborators

• Novartis Pharmaceuticals

  collaborator INDUSTRY

• Pfizer

  collaborator INDUSTRY

• Otsuka Pharmaceutical Co., Ltd.

  collaborator INDUSTRY

• University of California, San Francisco

  collaborator OTHER

• Westat

  collaborator OTHER

• National Institute of Allergy and Infectious Diseases (NIAID)

  collaborator NIH

• University of Colorado, Denver

  collaborator OTHER

• Harvard Medical School (HMS and HSDM)

  collaborator OTHER

• National Lung Hospital, Vietnam

  collaborator UNKNOWN

• De La Salle Health Sciences Institute, Philippines

  collaborator UNKNOWN

• Boston University

  lead OTHER

Principal Investigators

• Charles Horsburgh, MD · Boston University

• Payam Nahid, MD · University of California, San Francisco

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-06-07

Primary Completion

2027-05-31

Completion

2027-05-31

FDA Drug

Yes

Countries

• Philippines
• Vietnam

Study Locations