Overview

Evaluating Newly Approved Drugs in Combination Regimens for Multidrug-Resistant TB With Fluoroquinolone Resistance (endTB-Q)

Status:
Recruiting
Trial end date:
2024-07-01
Target enrollment:
0
Participant gender:
All
Summary
endTB-Q Clinical Trial is a Phase III, randomized, controlled, open-label, non-inferiority, multi-country trial evaluating the efficacy and safety of two new, all-oral, shortened regimens for multidrug-resistant tuberculosis (MDR-TB) with fluoroquinolone resistance.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Médecins Sans Frontières, France
Collaborators:
Epicentre
Harvard Medical School
Harvard Medical School (HMS and HSDM)
Institute of Tropical Medicine, Belgium
Interactive Research and Development
Partners in Health
Socios En Salud, Peru
University of San Francisco
Treatments:
Bedaquiline
Clofazimine
Diarylquinolines
Fluoroquinolones
Linezolid
Criteria
Inclusion Criteria:

1. Has documented pulmonary tuberculosis due to strains of M. tuberculosis resistant to
rifampin (RIF) and not susceptible to fluoroquinolones, according to a validated rapid
molecular test.

2. Is ≥15 years of age;

3. Is willing to use effective contraception: pre-menopausal women or women whose last
menstrual period was within the preceding year, who have not been sterilized must
agree to use two methods of contraception (e.g., a hormonal method and a barrier
method) 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:

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 breastfeeding an infant; 3. Is unable to
comply with treatment or follow-up schedule; 4. Has 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 definition 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 definition 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:

- Total Calcium <7.0 mg/dL (1.75 mmol/L);

- Potassium <3.0 mEq/L (3.0 mmol/L) or ≥6.0 mEq/L (6.0 mmol/L);

- Magnesium <0.9 mEq/L (0.45 mmol/L);

- Serum creatinine >3 x ULN;

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

- Total bilirubin ≥3 x ULN;

- Albumin <2.8 g/dL; Unless otherwise specified, Grade 4 result as defined by the MSF
Severity Scale on any of the screening laboratory tests.

7. Has cardiac risk factors defined as:

- An arithmetic average of the two ECGs with highest QTcF intervals of greater than or
equal to 450 ms. Retesting to reassess eligibility will be allowed 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 >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. Is currently taking part in another trial of a medicinal product;

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.