Study of a Single Dose of Pretomanid Added to an Optimized Background Regimen in Children With Rifampicin-Resistant Tuberculosis

NCT05586230 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IMPAACT 203438754
• Study Type: interventional
• Target: 72
• Locations: 4 countries
• Sites: 6

Brief Summary

The purpose of the study is to evaluate the pharmacokinetics (PK), safety, tolerability, and acceptability of a single dose of pretomanid, added to an optimized background tuberculosis treatment regimen (OBR), in children with rifampicin-resistant tuberculosis (RR-TB) with or without human immunodeficiency virus (HIV).

Conditions

Tuberculosis; Rifampicin Resistant Tuberculosis

Outcome Measures

Primary Outcomes (6)

• AUC0-∞

  Area under the curve from start of dose to infinity from start of dose to 48 hours post-dose. Measured from study entry to Day 2. Blood samples were drawn at 1, 3, 6, 9, 24 and 48 hours post dose

  Through 48 hours

• CL/F

  apparent clearance from start of dose to 48 hours post-dose. Measured from study entry to Day 2. Blood samples were drawn at 1, 3, 6, 9, 24 and 48 hours post dose

  Through 48 hours

• AUC0-tlast

  Area under curve-Last measure concentration from start of dose to 48 hours post-dose. Measured from study entry to Day 2. Blood samples were drawn at 1, 3, 6, 9, 24 and 48 hours post dose

  Through 48 hours

• AUC0-48

  Area under the curve from time zero to 48 hours from start of dose to 48 hours post-dose. Measured from study entry to Day 2. Blood samples were drawn at 1, 3, 6, 9, 24 and 48 hours post dose

  Through 48 hours

• Tmax

  Time of maximal concentration from start of dose to 48 hours post-dose. Measured from study entry to Day 2. Blood samples were drawn at 1, 3, 6, 9, 24 and 48 hours post dose

  Through 48 hours

• Cmax

  Peak concentration from start of dose to 48 hours post-dose. Measured from study entry to Day 2. Blood samples were drawn at 1, 3, 6, 9, 24 and 48 hours post dose

  Through 48 hours

Secondary Outcomes (5)

• Number of participants with an adverse event

  From time of single Pa dose at study entry to study week 2

• Number of participants with a Grade 3 or higher adverse event

  From time of single Pa dose at study entry to study week 2

• Number of participants with a grade 2 or higher adverse event assessed as related to study drug

  From time of single Pa dose at study entry to study week 2

• Number of participants with a serious adverse event

  From time of single Pa dose at study entry to study week 2

• Aggregated data on parent/guardian and/or participant (and/or study staff) reported palatability and acceptability of study drug given as single dose at entry

  At day 0

Study Arms (4)

Group 1 (≥ 31 kg)

EXPERIMENTAL

≥40 kg (Adult Formulation) 31-\<40 kg (Dispersible Pediatric Formulation)

Drug: Pretomanid; Drug: Optimized background regimen (OBR) for multidrug-resistant TB (MDR-TB)

Group 2 (20-<31 kg)

EXPERIMENTAL

20-\<31 kg (Dispersible pediatric Formulation)

Drug: Pretomanid; Drug: Optimized background regimen (OBR) for multidrug-resistant TB (MDR-TB)

Group 3 (12-<20 kg)

EXPERIMENTAL

12-\<20 kg (Dispersible pediatric Formulation)

Drug: Pretomanid; Drug: Optimized background regimen (OBR) for multidrug-resistant TB (MDR-TB)

Group 4 (4-<12 kg)

EXPERIMENTAL

8-\<12 kg (Dispersible pediatric Formulation) 6-\<8 kg (Dispersible pediatric Formulation) 4-\<6 kg (Dispersible pediatric Formulation)

Drug: Pretomanid; Drug: Optimized background regimen (OBR) for multidrug-resistant TB (MDR-TB)

Interventions

Pretomanid DRUG

Administered orally based on participant's weight

Also known as: Pa

Group 1 (≥ 31 kg); Group 2 (20-<31 kg); Group 3 (12-<20 kg); Group 4 (4-<12 kg)

Optimized background regimen (OBR) for multidrug-resistant TB (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 single dose of Pa.

Group 1 (≥ 31 kg); Group 2 (20-<31 kg); Group 3 (12-<20 kg); Group 4 (4-<12 kg)

Eligibility Criteria

• Age: Up to 17 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• If not of legal age or circumstance to provide independent informed consent as determined by site standard operating procedures (SOPs) and consistent with institutional review board/ethics committee (IRB/EC) policies and procedures: Parent/legal guardian is willing and able to provide written informed consent for potential participant's study participation; in addition, when applicable per IRB/EC policies and procedures, potential participant is willing and able to provide written assent for study participation.
• If of legal age or circumstance to provide independent informed consent as determined by site SOPs and consistent with IRB/EC policies and procedures: Potential participant is willing and able to provide written informed consent for study participation.
• Note: All sites must follow all applicable IRB/EC policies and procedures.
• Assigned female sex at birth, as determined by the site investigator based on participant and parent/guardian report and available medical records
• Age less than 18 years of age at entry
• Note: Neonates (defined as children who are 28 days of age or younger \[≤28 days of age\]) may be allowed to enroll after CMC and SMC evaluation of safety and PK data at the interim analysis.
• Weight greater than or equal to 4 kg at entry
• Confirmed intrathoracic (pulmonary) RR-TB, based on chest radiograph and/or symptoms consistent with TB, and/or any forms of extrathoracic TB, with all of the following, as determined by the site investigator based on medical records:
• Microbiological confirmation of M. tuberculosis from any clinical specimen by either culture or molecular methods
• Rifampicin resistance demonstrated by genotypic (molecular) or phenotypic methods
• Documented clinical decision to treat for RR-TB
• Note: In the case of discrepant genotypic and phenotypic test results (i.e., rifampicin-susceptible by one method and rifampicin-resistant by another), this criterion will be considered to have been met if at least one rifampicin-resistant result is available and the participant is assessed as having RR-TB by the non-study care provider when study staff evaluate the participant for eligibility.
• Probable intrathoracic (pulmonary) RR-TB, based on chest radiograph and/or symptoms consistent with TB, and/or any form of extrathoracic TB, with both of the following, as determined by the site investigator based on medical records:
• Documented exposure to a source case with bacteriologically-confirmed intrathoracic rifampicin-resistant TB
• Documented clinical decision to treat for RR-TB

You may not qualify if:

• Has tuberculosis meningitis Stage 2 or 3, as determined by the site investigator based on medical records
• Receipt of any of the following, within 14 days prior to entry, as determined by the site investigator based on participant/parent/guardian report and available medical records
• Rifamycins
• Any prohibited medication (see protocol for listing)
• For participants living with HIV: ritonavir-boosted protease inhibitors (e.g., ritonavir-boosted lopinavir, ritonavir-boosted darunavir), atazanavir, nevirapine etravirine, efavirenz, or cobicistat
• Receipt of any investigational agent or device within 28 days prior to entry, as determined by the site investigator based on participant/parent/guardian report and available medical records
• Note: Co-enrollment in COVID-19 vaccine studies and receipt of a COVID-19 vaccine under emergency use authorization (or local equivalent) is allowed, with prior approval from the CMC.
• Note: Any co-enrollment must be approved as noted in protocol
• Has any of the following as determined by the site investigator based on participant/ parent/guardian report and available medical records
• Clinical evidence of acute hepatitis A, B, C, or chronic hepatitis B or C
• Significant cardiac arrhythmia that requires medication or increases the risk for Torsade de Pointes
• Known allergy or hypersensitivity to pretomanid or other nitroimidazole compounds
• Known porphyria
• Currently breastfeeding an infant at entry, as determined by the site investigator based on participant/parent/guardian report
• Exposed to pretomanid through breast milk within seven days prior to entry (i.e., mother receiving pretomanid and breastfeeding a potential participant), as determined by the site investigator based on parent/guardian report

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute of Mental Health (NIMH): collaborator
• Global Alliance for TB Drug Development: collaborator

Study Sites (6)

Site 5071, Instituto de Puericultura e Pediatria Martagao Gesteira CRS

Rio de Janeiro, Brazil

RECRUITING

Site 31441, BJMC CRS

Pune, India

NOT YET RECRUITING

Site 31976, PHRU Matlosana CRS

Klerksdorp, North West, 2574, South Africa

ACTIVE NOT RECRUITING

Site 31790, Desmond Tutu TB Centre (DTTC) CRS

Cape Town, South Africa

ACTIVE NOT RECRUITING

Site 31929, Sizwe CRS

Johannesburg, South Africa

ACTIVE NOT RECRUITING

Site 5115, Siriraj Hospital, Mahidol University NICHD CRS

Bangkok Noi, Thailand

RECRUITING

Related Links

• Related Info

MeSH Terms

Conditions

Tuberculosis

Interventions

pretomanid

Condition Hierarchy (Ancestors)

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

Study Officials

• Ethel Weld

  Johns Hopkins University

  STUDY CHAIR

Central Study Contacts

IMPAACT Clinicaltrials.gov Coordinator

CONTACT

impaact.ctgov@fstrf.org

Katie McCarthy

CONTACT

(919) 321-3326; kmccarthy@fhi360.org

Study Design

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

Study Record Dates

• First Submitted: October 11, 2022
• First Posted: October 19, 2022
• Study Start: October 3, 2023
• Primary Completion: May 2, 2026
• Study Completion: May 2, 2026
• Last Updated: March 23, 2026

Record last verified: 2025-05

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

ZA (3); BR (1); TH (1); IN (1)