Evaluating the Pharmacokinetics, Safety, and Tolerability of Delamanid in Combination With Optimized Multidrug Background Regimen (OBR) for Multidrug-Resistant Tuberculosis (MDR-TB) in HIV-Infected and HIV-Uninfected Children With MDR-TB

NCT03141060 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: IMPAACT 200520721
• Study Type: interventional
• Target: 37
• Locations: 3 countries
• Sites: 5

Brief Summary

This study will evaluate the pharmacokinetics, safety, and tolerability of the anti-tuberculosis (TB) drug delamanid (DLM) in combination with an optimized multidrug background regimen (OBR) for multidrug-resistant tuberculosis (MDR-TB) in HIV-infected and HIV-uninfected children with MDR-TB.

Conditions

Tuberculosis; HIV Infections

Outcome Measures

Primary Outcomes (5)

• Frequency of Grade 3 or 4 adverse events (AEs)

  Based on labs, signs/symptoms, diagnoses

  Measured through Week 24

• Frequency of Grade 3 or 4 AEs judged by the Clinical Management Committee (CMC) to be related to DLM

  Based on labs, signs/symptoms, diagnoses

  Measured through Week 24

• Frequency of permanent discontinuations of DLM due to a toxicity or AE

  Based on study drug discontinuation criteria outlined in the protocol

  Measured through Week 24

• Frequency of QTcF interval greater than or equal to 500 ms

  Based on electrocardiogram (ECG)

  Measured through Week 24

• Frequency of participant deaths

  Grade 5 event

  Measured through Week 24

Secondary Outcomes (8)

• Frequency of Grade 3 or 4 AEs

  Measured through Week 72

• Frequency of Grade 3 or 4 AEs judged by the CMC to be related to DLM

  Measured through Week 72

• Frequency of permanent discontinuations of DLM due to a toxicity or AE

  Measured through Week 72

• Frequency of QTcF interval greater than or equal to 500 ms

  Measured through Week 72

• Frequency of participant deaths

  Measured through Week 72

Study Arms (1)

Arm 1: Delamanid

EXPERIMENTAL

Participants will receive delamanid (DLM) twice daily for 24 weeks. Participants will also receive non-study prescribed OBR for MDR-TB.

Drug: Delamanid; Drug: Optimized multidrug background regimen (OBR) for children with MDR-TB

Interventions

Delamanid DRUG

Administered orally; dosing will be based on participants' age and weight.

Also known as: DLM

Arm 1: Delamanid

Optimized multidrug background regimen (OBR) for children with MDR-TB DRUG

Non-study prescribed OBR will vary according to local, national, and/or international guidelines for treatment of children with MDR-TB. Administered in addition to DLM for 24 weeks.

Arm 1: Delamanid

Eligibility Criteria

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

You may qualify if:

• Parent (or legal guardian) is willing and able to provide written informed consent for child study participation. Additionally, for children whose assent is required per site institutional review board/ethics committee (IRB/EC) policies and procedures, child is willing and able to provide written assent for his or her study participation.
• Age less than 18 years at enrollment
• HIV-uninfected, or HIV-infected (see the protocol for more information on this criterion)
• If HIV-infected: Initiated the standard of care antiretroviral therapy (ART) regimen at least two weeks prior to enrollment (note: regimens including efavirenz \[EFV\], nevirapine \[NVP\], a boosted protease inhibitor \[PI\], or integrase strand transfer inhibitor \[INSTI\] are allowed)
• Confirmed or probable MDR-TB classified as follows:
• Confirmed MDR-TB (or rifampicin mono-resistant TB \[RMR-TB\], pre-extensively drug-resistant \[XDR\] or XDR-TB):
• Intra-thoracic (pulmonary) TB based on chest radiograph consistent with TB, and/or any of the following forms of extrathoracic TB:
• \) Peripheral TB lymphadenitis
• \) Pleural effusion or fibrotic pleural lesions
• \) Stage 1 TB meningitis
• \) Miliary and abdominal TB
• AND
• Microbiological confirmation of Mycobacterium tuberculosis from any clinical specimen by either culture or molecular methods (including Xpert MTB/RIF)
• AND
• Drug-resistance demonstrated by genotypic (molecular) or phenotypic methods, with any of the following resistance patterns:

You may not qualify if:

• Known allergy to any nitroimidazoles or nitroimidazole derivatives
• Active use of prohibited medications listed in the protocol, within 3 days of enrollment
• Participant has a history of any of the following, as determined by the site investigator or designee based on maternal report and available medical records:
• A significant cardiac arrhythmia that requires medication or a history of heart disease (heart failure, coronary artery disease) that increases the risk for Torsade de Pointes
• Significant gastrointestinal (GI), metabolic, neuropsychiatric, kidney or endocrine disease at screening that would, in the investigator's opinion, preclude safe participation in the trial and/or assessment of primary endpoints
• Previous DLM or pretomanid exposure
• Note: Participants can have received up to 14 + 3 days (i.e., up to 17 days) of DLM prior to enrollment
• Abnormal electrocardiogram (ECG) (including QTcF \[mean value of QT interval, corrected using Fredericia correction, on ECG performed in triplicate\] greater than or equal to 450 ms, atrioventricular block, or prolonged QRS greater than or equal to 120 ms) at screening
• Karnofsky score less than 30% for participants greater than or equal to 16 years of age or Lansky play score less than 30% for participants less than 16 years of age, at screening
• Alcohol intake that in the opinion of the study investigator could potentially interfere with study participation and/or introduce safety concerns with use of DLM
• Lactating with plans to breastfeed, at enrollment
• Tuberculous meningitis (TBM) Stage 2 or 3, or osteo-articular TB at screening
• Co-enrolled in any other trial involving pharmacologic regimens, at screening
• If HIV-exposed and less than 2 years of age: Breastfeeding at enrollment

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Otsuka Pharmaceutical Development & Commercialization, Inc.: collaborator

Study Sites (5)

Byramjee Jeejeebhoy Medical College (BJMC) CRS

Pune, Maharashtra, 411001, India

Location

Sizwe CRS

Johannesburg, Gauteng, South Africa

Location

PHRU Matlosana CRS

Klerksdorp, North West, 2574, South Africa

Location

Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS

Cape Town, Western Cape, 7505, South Africa

Location

Kilimanjaro Christian Medical Centre (KCMC)

Moshi, Tanzania

Location

Related Links

• Related Info

MeSH Terms

Conditions

Tuberculosis; HIV Infections

Interventions

OPC-67683

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Anthony Garcia-Prats, MD

  University of Stellenbosch

  STUDY CHAIR

• Ethel Weld, MD

  Johns Hopkins University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2017
• First Posted: May 4, 2017
• Study Start: January 30, 2018
• Primary Completion: April 22, 2025
• Study Completion: May 29, 2025
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network. * For what types of analyses? * To achieve aims in the proposal approved by the IMPAACT Network. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/resources/study-proposals.htm. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.

Locations

TA (1); ZA (3); IN (1)