Pharmacokinetic Study to Evaluate Anti-mycobacterial Activity of TMC207 in Combination With Background Regimen (BR) of Multidrug Resistant Tuberculosis (MDR-TB) Medications for Treatment of Children/Adolescents With Pulmonary MDR-TB

NCT02354014 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: CR106371TMC207-TIDP59-C2112014-003372-23
• Study Type: interventional
• Target: 60
• Locations: 6 countries
• Sites: 11

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (explores what the body does to the drug), and anti-mycobacterial activity of bedaquiline (TMC207) in children and adolescents (0 months to less than \[\<\] 18 years of age) diagnosed with confirmed or probable pulmonary multidrug resistant tuberculosis (MDR-TB), in combination With a Background Regimen (BR) of MDR-TB Medications.

Conditions

Tuberculosis, Multidrug-Resistant

Keywords

Multidrug-Resistant Tuberculosis; Bedaquiline; TMC207

Outcome Measures

Primary Outcomes (9)

• Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)

  An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  Cohort 1 to 3 = up to 120 Weeks and Cohort 4 = up to 88 Weeks

• Maximum Plasma Concentration (Cmax)

  The Cmax is the maximum plasma concentration.

  Week 2 and 12

• Time to Reach Maximum Plasma Concentration (Tmax)

  The Tmax is time to reach the maximum plasma concentration.

  Week 2 and 12

• Minimum Plasma Concentration (Cmin)

  The Cmin is the minimum plasma concentration.

  Week 2, 12 and 24

• Area Under the Plasma Concentration-time Curve From the Time of Dose Administration up to X Hours (AUCtime-h)

  AUCtime-h is the area under the plasma concentration-time curve from the time of dose administration up to X hours.

  Week 2, 12 and 24

• Elimination Half-life (t1/2)

  Elimination half-life (t \[1/2\]) is associated with the terminal slope (lambda \[z\]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z). Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.

  For Cohorts 1 to 3: Day 1, Weeks 2, 4,6,8,12,16,20,24,28,32,40,48,60,72,84,96,108,120; For Cohort 4: Day 1, Weeks 2,12, 24, 32, 48, 88

• Area Under the Plasma Concentration-time Curve From the Time of Dose Administration up to 168 Hours [AUC168h]

  AUC168h is the area under the plasma concentration-time curve from the time of dose administration up to 168 Hours.

  Week 12 and 24

• Volume of Distribution (Vd)

  Volume of distribution is calculated as Dose divided by Lambda(z) multiplied by AUC(infinity). The AUC (infinity) is the area under the plasma concentration-time curve from time zero to infinite time.

  For Cohorts 1 to 3: Day 1, Weeks 2, 4,6,8,12,16,20,24,28,32,40,48,60,72,84,96,108,120; For Cohort 4: Day 1, Weeks 2,12, 24, 32, 48, 88

• Apparent Clearance (CL)

  Apparent clearance is calculated as Dose/AUC (infinity). The AUC (infinity) is the area under the plasma concentration-time curve from time zero to infinite time.

  For Cohorts 1 to 3: Day 1, Weeks 2, 4,6,8,12,16,20,24,28,32,40,48,60,72,84,96,108,120; For Cohort 4: Day 1, Weeks 2,12, 24, 32, 48, 88

Secondary Outcomes (3)

• Percentage of Participants with Favorable Treatment outcome (Sustained Clinical Cure)

  Week 24, Week 120 (for Cohorts 1 to 3) and Week 88 (for Cohort 4)

• Time to First Confirmed Mycobacteria Growth Indicator Tube (MGIT) Culture Conversion of Clinical Specimen Sample

  Baseline (Day 1), up to Week 120 (for Cohorts 1 to 3), Week 88 (for Cohort 4)

• Time to Acid-Fast Bacilli (AFB) Smear Conversion of Clinical Specimen Sample

  Baseline (Day 1), up to Week 120 (for Cohorts 1 to 3), Week 88 (for Cohort 4)

Study Arms (1)

Bedaquiline (TMC207)/Background Regimen (BR)

EXPERIMENTAL

There will be 4 age-based cohorts. Participants will be enrolled concurrently in Cohorts 1 and 2 followed by sequential enrollment of Cohorts 3, 4. Cohort 1: \>= 12 to \< 18 years: bedaquiline (TMC207) tablet orally as 400 mg, once daily(qd),for first 2 weeks, followed by bedaquiline (TMC207), 200 mg 3 times per week (tiw) for 22 weeks; Cohort 2: \>=5 to \<12 years: bedaquiline (TMC207) tablet given orally as 200 mg, qd, for first 2 weeks, followed by bedaquiline (TMC207) 100 mg, tiw for 22 weeks. Cohort 3: \>=2 to \<5 years: bedaquiline (TMC207) 8 milligram per kilogram (mg/kg) qd for the first 2 weeks, followed by bedaquiline (TMC207) 4 mg/kg tiw for 22 weeks. Cohort 4: 0 months to \<2 years: bedaquiline (TMC207) doses will be selected as per weight band and age group. Bedaquiline (TMC207) will be given in combination with Background Regimen for Multidrug Resistant Tuberculosis (MDR-TB) according to WHO/national tuberculosis program (NTP) guidelines/current standard of care.

Drug: Bedaquiline (TMC207); Drug: Background Regimen (BR)

Interventions

Bedaquiline (TMC207) DRUG

Bedaquiline (TMC207) oral tablet adult formulation (containing 100 mg bedaquiline (TMC207) per tablet) administered as 400 milligram (mg), once daily, for the first 2 weeks, followed by bedaquiline 200 mg 3 times per week with intakes at least 2 days (48 hours) apart for 22 weeks in cohort 1. Cohort 2, 3 and 4 will receive an age appropriate oral tablet formulation containing 20mg bedaquiline . Bedaquiline tablet administered orally as 200 mg, once daily, for the first 2 weeks, followed by bedaquiline 100 mg 3 times per week with intakes at least 2 days (48 hours) apart for 22 weeks in cohort 2. In Cohort 3, dose of bedaquiline 8 mg/kg qd for the first 2 weeks, followed by bedaquiline 4 mg/kg times weekly (TIW) with intakes at least 2 days (48 hours) apart for 22 weeks will be administered. In cohort 4, bedaquiline (TMC207) qd for the first 2 weeks, followed by bedaquiline TIW with intakes at least 2 days (48 hours) apart for 22 weeks.

Also known as: Bedaquiline

Bedaquiline (TMC207)/Background Regimen (BR)

Background Regimen (BR) DRUG

Background Regimen (BR) of Multidrug Resistant Tuberculosis (MDR-TB) medications will be dosed according to World Health Organization (WHO) guidelines, National Tuberculosis Program (NTP) guidelines and current standard of care at the site.

Bedaquiline (TMC207)/Background Regimen (BR)

Eligibility Criteria

• Age: 0 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participant must be a boy or girl, aged from birth (0 months) to less than (\<) 18 years at screening. Participants in Cohort 4 who are \<6 months of age at screening, gestational age at birth had to be greater than or equal to (\>=) 37 weeks
• Participant must weigh \>3 kilogram (kg) at baseline and be within the 5th and 95th percentiles (inclusive) for the participant's age, based on the World Health Organization (WHO) child growth standards; Body Mass Index (BMI) for age. In Cohorts 3 and 4, weight for height/length may be used instead of BMI for age according to the local standard of care. Per WHO guidance, for participants aged \< 2 years in Cohort 4, length will be used to calculate the BMI instead of height
• For Cohorts 1 and 2 only: Heterosexually active girls may participate if they are of non-childbearing potential, or if they are using effective birth control methods and are willing to continue practicing birth control methods throughout Multidrug Resistant Tuberculosis (MDR-TB) treatment and for 6 months after stopping TMC207 treatment, or if they are non-heterosexually active or willing to practice sexual abstinence throughout MDR-TB treatment
• For Cohorts 1 and 2 only: Boys who engage in sexual activity that could lead to pregnancy of the female partner must use at minimum a male condom throughout MDR-TB treatment and for 3 months after stopping TMC207 treatment
• Participant must have confirmed or probable (clinically diagnosed or presumed) pulmonary and/or non-severe extrapulmonary MDR-TB, including pre-extensively drug-resistant TB (pre- extensively drug resistant \[XDR\]-TB) or XDR-TB infection, based on the case definitions of pediatric pulmonary and non-severe extrapulmonary TB as described in the International (WHO) guidelines and in accordance with the local standard of care
• Participants must be starting the initial MDR-TB treatment at Day 1 or have started an MDR-TB treatment within 12 weeks of Day 1 and are willing to modify it if necessary to an acceptable MDR-TB regimen for use with TMC207
• Participant must be willing to permanently discontinue RMP from at least 7 days before the baseline visit
• Participant or legally acceptable representative must consent/assent to human Immunodeficiency virus (HIV) testing of the participant. The mother must also consent to testing of her own HIV status, if the potential participant is a child aged \<2 years, or if the participant is \>= 2 years old and being breastfed or was breastfed within the last 8 weeks before screening, unless the mother had HIV test performed within 1 month prior to screening and documentation of HIV status can be provided. When documented HIV-positive status is available prior to screening for participants in Cohort 4 or their mother, HIV testing for the participant and mother is not required

You may not qualify if:

• Participant has a clinically significant active medical condition or the presence of any concomitant severe illness or rapidly deteriorating health condition, including immune deficiency (except HIV infection), which in the opinion of the investigator would prevent appropriate participation in the study, or that would make implementation of the protocol or interpretation of the study results difficult, or otherwise make the subject a poor candidate for a clinical study
• Participant is a girl who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 6 months after stopping TMC207 treatment
• Participant has known or presumed forms of extrapulmonary TB, other than: Lymphadenopathy (peripheral nodes or isolated mediastinal mass without significant airway compression); Pleural effusion or pleural fibrotic lesions
• Participant has a significant cardiac arrhythmia that requires medication or risk factors for Torsade de Pointes, example heart failure, hypokalemia, known personal or family history of Long QT Syndrome, and untreated hypothyroidism

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (11)

Hospital Geral da Polana Caniço

Maputo, 00000, Mozambique

RECRUITING

De La Salle Health Sciences Institute- DLSUMC

Dasmariñas, 4114, Philippines

RECRUITING

Lung Center Of The Philippines

Quezon City, 1100, Philippines

COMPLETED

Silang Specialists Medical Center

San Vincent Silang, 000, Philippines

RECRUITING

First Moscow State Medical University n.a. I.M. Sechenov

Moscow, 119991, Russia

COMPLETED

THINK: Tuberculosis & HIV Investigative Network

Durban, 4001, South Africa

COMPLETED

Sizwe Tropical Diseases Hospital

Johannesburg, 2131, South Africa

RECRUITING

Wits Health Consortium

Port Elizabeth, 6200, South Africa

RECRUITING

Desmond Tutu TB Centre

Stellenboch, 7600, South Africa

RECRUITING

Makerere University Lung Institute

Kampala, Uganda

TERMINATED

State Institute Of Phthisiology And Pulmonology N.A. F.G. Yanovskiy Of Ams Ukraine

Kiev, 3038, Ukraine

COMPLETED

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Interventions

bedaquiline

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Central Study Contacts

Study Contact

CONTACT

Participate-In-This-Study1@its.jnj.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2015
• First Posted: February 3, 2015
• Study Start: May 3, 2016
• Primary Completion (Estimated): February 11, 2027
• Study Completion (Estimated): November 2, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

PH (3); ZA (4); RU (1); UG (1); MO (1); UA (1)