Evaluating Newly Approved Drugs for Multidrug-resistant TB

• Register: ClinicalTrials.gov
• Last refreshed on: 4 September 2023
• Main ID: NCT02754765
• Date of registration: 25/04/2016
• Prospective Registration: Yes
• Primary sponsor: Médecins Sans Frontières, France
• Public title: Evaluating Newly Approved Drugs for Multidrug-resistant TB endTB
• Scientific title: Evaluating Newly Approved Drugs for Multidrug-resistant TB (endTB): A Clinical Trial
• Date of first enrolment: December 2016
• Target sample size: 754
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02754765
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Georgia, India, Kazakhstan, Kyrgyzstan, Lesotho, Pakistan, Peru, South Africa

Contacts

• Name: Carole Mitnick, Sc.D
• Affiliation: Harvard Medical School (HMS and HSDM)

• Name: Lorenzo Guglielmetti, MD
• Affiliation: Médecins Sans Frontières, France

Key inclusion & exclusion criteria

Inclusion Criteria:

A patient will be eligible for randomization if s/he:

1. Has documented pulmonary tuberculosis due to strains of M. tuberculosis resistant to
rifampin (RIF) and susceptible to fluoroquinolones, diagnosed by validated rapid
molecular test;

2. Is = 15 years of age;

3. Is willing to use contraception: pre-menopausal women or women whose last menstrual
period was within the preceding year, who have not been sterilized must agree to use
contraception unless their partner has had a vasectomy; men who have not had a
vasectomy must agree to use condoms;

4. Provides informed consent for study participation; additionally a legal representative
of patients considered minor per local laws should also provide consent;

5. Lives in a dwelling that can be located by study staff and expects to remain in the
area for the duration of the study.

Exclusion Criteria:

A patient will not be eligible for randomization if s/he:

1. Has known allergies or hypersensitivity to any of the investigational drugs;

2. Is known to be pregnant or is unwilling or unable to stop breast-feeding an infant;

3. Is unable to comply with treatment or follow-up schedule;

4. Any condition (social or medical) which, in the opinion of the site principal
investigator, would make study participant unsafe;

5. a. Has had exposure (intake of the drug for 30 days or more) in the past five years to
bedaquiline, delamanid, linezolid, or clofazimine, or has proven or likely resistance
to bedaquiline, delamanid, linezolid, or clofazimine (e.g., household contact of a
DR-TB index case who died or experienced treatment failure after treatment containing
bedaquiline, delamanid, linezolid, or clofazimine or had resistance to one of the
listed drugs); exposure to other anti-TB drugs is not a reason for exclusion.

b. Has received second-line drugs for 15 days or more prior to screening visit date in
the current MDR/RR-TB treatment episode. Exceptions include: (1) patients whose
treatment has failed according to the WHO definition151 and who are being considered
for a new treatment regimen; (2) patients starting a new treatment regimen after
having been "lost to follow-up" according to the WHO definition149 and, (3) patients
in whom treatment failure is suspected (but not confirmed according to WHO
definition), who are being considered for a new treatment regimen, and for whom the
Clinical Advisory Committee (CAC) consultation establishes eligibility.

6. Has one or more of the following:

- Hemoglobin = 7.9 g/dL;

- Uncorrectable electrolytes disorders:

- Calcium < 7.0 mg/dL;

- Potassium < 3.0 or =6.0 mEq/L;

- Magnesium < 0.9 mEq/L;

- Serum creatinine > 3 x ULN;

- Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) = 3 x ULN;

- Total bilirubin = 1.5 x ULN if accompanied by AST or ALT > ULN or total bilirubin
= 2 x ULN when other liver function results are in the normal range;

- Grade 4 result on any of the specified laboratory tests as defined by the MSF
Severity Scale.

7. Has cardiac risk factors defined as:

- A confirmed QTc interval of greater than or equal to 450 ms. Retesting to
reassess eligibility will be allowed once using an unscheduled visit during the
screening phase;

- Evidence of ventricular pre-excitation (e.g., Wolff Parkinson White syndrome);

- Electrocardiographic evidence of either:

- Complete left bundle branch block or right bundle branch block; OR

- Incomplete left bundle branch block or right bundle branch block and QRS
complex duration greater or equal to 120 msec on at least one ECG;

- Having a pacemaker implant;

- Congestive heart failure;

- Evidence of second or third degree heart block;

- Bradycardia as defined by sinus rate less than 50 bpm;

- Personal or family history of Long QT Syndrome;

- Personal history of arrhythmic cardiac disease, with the exception of sinus
arrhythmia;

- Personal history of syncope (i.e. cardiac syncope not including syncope due to
vasovagal or epileptic causes).

8. Concurrent participation in another trial of any medication used or being studied for
TB treatment, as defined in cited documents.

9. Is taking any medication that is contraindicated with the medicines in the trial
regimen which cannot be stopped (with or without replacement) or requires a wash-out
period longer than 2 weeks.



Age minimum: 15 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Tuberculoses

Tuberculosis, Multidrug-Resistant

Infection, Bacterial

Intervention(s)

Drug: Bedaquiline

Drug: Levofloxacin

Drug: Control arm MDR-TB regimen, consistent with WHO guidelines

Drug: Linezolid

Drug: Clofazimine

Drug: Pyrazinamide

Drug: Delamanid

Drug: Moxifloxacin

Primary Outcome(s)

Week 73 Efficacy [Time Frame: Week 73 after randomization]

Secondary Outcome(s)

Early Treatment Response (culture conversion) [Time Frame: Week 8 after randomization]

Week 104 Efficacy [Time Frame: Week 104 after randomization]

Week 39 Efficacy [Time Frame: Week 39 after randomization]

Week 73 Survival [Time Frame: Week 73 after randomization]

Week 73 Safety [Time Frame: Week 73 after randomization]

Week 104 Safety: proportion of patients with AESIs [Time Frame: Week 104 after randomization]

Week 104 Survival [Time Frame: Week 104 after randomization]

Week 73 Safety: proportion of patients with AESIs [Time Frame: Week 73 after randomization]

Week 104 Safety [Time Frame: Week 104 after randomization]

Secondary ID(s)

MSF ERB-1555

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Epicentre

Harvard Medical School (HMS and HSDM)

Institute of Tropical Medicine, Belgium

Interactive Research and Development

Partners in Health

Socios En Salud, Peru