New treatment approach for multidrug-resistant tuberculosis
Prospective, Randomized, Partially Blinded, Phase 2 Study of the Efficacy and Tolerability of Bedaquiline, Delamanid, Levofloxacin, Linezolid, and Clofazimine for Treatment of Patients With MDR-TB
This study is testing a new all-oral treatment for multidrug-resistant tuberculosis to see if it can be safer and more effective than current options.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 220 (estimated) |
| Ages | 12 Years and up |
| Sex | All |
| Sponsor | Boston University Academic / other |
| Locations | 2 sites (Dasmariñas and 1 other locations) |
| Trial ID | NCT03828201 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the efficacy and safety of a novel all-oral regimen consisting of bedaquiline, delamanid, levofloxacin, linezolid, and clofazimine for treating multidrug-resistant tuberculosis (MDR-TB). The study is a multicenter, randomized, partially blinded, four-arm phase 2 trial that aims to determine the optimal duration of treatment while minimizing toxicity. Participants will receive treatment for varying durations of 16, 24, 32, or 40 weeks, with a focus on improving tolerability and reducing the need for injectable agents. The trial addresses significant challenges in current MDR-TB treatment regimens, which are often lengthy and associated with severe side effects.
Who should consider this trial
Good fit: Ideal candidates for this study are individuals aged 12 years and older with pulmonary tuberculosis that is rifamycin-resistant and fluoroquinolone-susceptible.
Not a fit: Patients with tuberculosis that is not resistant to rifamycin or fluoroquinolone may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a shorter and less toxic option for patients suffering from multidrug-resistant tuberculosis.
How similar studies have performed: Other studies have explored similar treatment regimens for MDR-TB, but this specific combination and approach is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Males and females age ≥12 years. Prior to study procedures, if ≥18 years of age, provides informed consent; if \<18 years of age, child provides informed assent and has a parent or guardian who provides informed consent on the participant's behalf.
2. Has pulmonary TB based on investigator assessment of all available information (e.g., chest radiograph, sputum smear, culture, molecular testing).
3. Has a sputum sample that is positive for M. tuberculosis that is rifamycin-resistant and fluoroquinolone-susceptible by molecular assay.
4. Is HIV seropositive or seronegative; HIV serostatus must be assessed at screening if either (a) HIV serostatus is unknown, or (b) the last documented negative HIV test was more than two (2) months prior to screening.
5. Willing to attend scheduled follow-up visits and undergo study assessments.
6. Participants of child-bearing potential must agree either (a) to practice an adequate birth control (defined as one of the following oral contraceptives, intrauterine devices, contraceptive implants under the skin, contraceptive rings or patches or injections, diaphragms with spermicide or condoms with foam) or (b) to abstain from heterosexual intercourse during study regimen.
Exclusion Criteria:
1. Current MTB isolate is known at screening to be fluoroquinolone-resistant.
2. History of allergy (hypersensitivity) or intolerability to one or more agents in the investigational regimens (i.e., Arms 1 and 2)
3. History of serotonin syndrome
4. History of symptomatic ventricular arrhythmia or is taking anti-arrhythmic agents
5. History of optic neuropathy or peripheral neuropathy
6. History of Ehlers-Danlos Syndrome, Marfan Syndrome or aortic aneurism
7. History of prior treatment with delamanid or linezolid for TB for greater than one month.
8. Has at screening received ≥14 days of second-line anti-TB drugs during current TB episode
9. Has at screening a Karnofsky score of ≤40 or, in the opinion of the Investigator, is unlikely to survive 76 weeks.
10. Has at screening laboratory results that meet one or more of the following criteria:
* Hemoglobin concentration 8.0 g/dL (\<80 g/L)
* Platelet count of \<80,000/mm3
* Absolute neutrophil count (ANC) \<2000/ mm3
* Serum creatinine \>2.0 mg/dL (\>177 µmol/L)
* Serum ALT \>3x upper limit of normal (ULN)
* Total bilirubin \>3x upper limit of normal (ULN)
* Serum albumin \<2.8 g/dL (\<28 g/L)
* For women of childbearing potential, a positive or indeterminate serum pregnancy test
11. For women of childbearing potential, has a positive or indeterminate urine pregnancy test on the day of randomization.
12. Has at screening a mean QTcF \>450 msec based on three ECGs.
13. At screening requires ongoing use of prohibited drugs indicated in section 4.2
14. At screening, has weight less than 33 Kg
15. In the investigator's judgement is unable to provide consent (if ≥18 years of age) or unable to provide assent (if \>12 years of age).
16. History of congestive heart failure
Where this trial is running
Dasmariñas and 1 other locations
- De La Salle Health Sciences Institute — Dasmariñas, Philippines (Recruiting)
- National Lung Hospital — Hanoi, Vietnam (Recruiting)
Study contacts
- Principal investigator: Charles Horsburgh, MD — Boston University
- Study coordinator: Pawandeep Kaur, MPH
- Email: kaurp@bu.edu
- Phone: (617) 358-2421
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.