A Trial to Evaluate the Male Reproductive Safety of Pretomanid in Adult Male Participants With Drug Resistant Pulmonary Tuberculosis

NCT04179500 | Completed Phase 2 Results FDA Drug

• 1 other identifier: Pa-824-CL-012
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 4

Brief Summary

Pretomanid is being used in an antimicrobial combination regimen(s) to treat patients with pulmonary tuberculosis (TB). The primary purpose of the Male Reproductive Safety - "BPaMZ/SEM"- clinical study is to evaluate the potential effect of pretomanid on human testicular function whilst being used in a 26 weeks antimicrobial combination regimen consisting of bedaquiline (B) plus pretomanid (Pa) plus moxifloxacin (M) and pyrazinamide (Z) (BPaMZ).

Conditions

Tuberculosis, Pulmonary; Tuberculosis, Multidrug-Resistant; Tuberculosis, MDR; Tuberculosis; Drug-Resistant Tuberculosis

Keywords

tuberculosis; TB; DR-TB; pretomanid (PA); PA-824; XDR TB; Pa

Outcome Measures

Primary Outcomes (1)

• Change Form Baseline Total Sperm Count

  Change from baseline in total sperm number at 26 weeks of therapy. Total sperm count is calculated by multiplying the sperm cell concentration by the ejaculate volume.

  Week 26

Secondary Outcomes (6)

• Change From Baseline in Total Sperm Count at 12 Weeks

  Baseline to Week 12

• Change From Baseline Total Sperm Count at 44 Weeks

  Baseline through 44 weeks

• Luteinizing Hormone (LH)

  Baseline to Week 78

• FSH

  Baseline to week 78

• Testosterone

  Baseline to 78 weeks

Study Arms (1)

Study Participants

EXPERIMENTAL

Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.

Drug: Pretomanid; Drug: Bedaquiline; Drug: moxifloxacin; Drug: pyrazinamide

Interventions

Pretomanid DRUG

pretomanid 200 mg (once daily) for 26 weeks (with meal)

Also known as: Pa-824, Doprevla, Pa

Study Participants

Bedaquiline DRUG

bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)

Also known as: Sirturo, B

Study Participants

moxifloxacin DRUG

moxifloxacin 400 mg (once daily) for 26 weeks (with meal)

Also known as: Avelox, M

Study Participants

pyrazinamide DRUG

pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)

Also known as: Pyzina, Tebrazid, Z

Study Participants

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: males 18 years of age or older
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understands study procedures and voluntarily provides written informed consent prior to the start of any study-specific procedures.
• Male gender 18 years or over
• Body weight (in light clothing and no shoes) ≥ 45kg.
• A positive molecular test for tuberculosis in sputum either at screening or within one month prior to enrolment.
• Disease Characteristics:
• Participants must have been diagnosed with TB prior to or at screening
• Participants' TB should be resistant to rifampicin and/or isoniazid, and susceptible to fluoroquinolones by rapid sputum-based tests.
• Participants who have had previous treatment for DR-TB for more than 3 months at start of screening should be discussed with the medical monitor.
• A chest x-ray, within 26 weeks prior to or at the screening visit, which in the opinion of the Investigator is compatible with pulmonary TB

You may not qualify if:

• Resistant to fluoroquinolones by rapid molecular test
• History of male infertility or vasectomy
• Unable to produce semen sample
• Evidence at screening of azoospermia
• Known erectile dysfunction that would prevent ejaculation.
• Historical or active disease process of the male reproductive tract that would compromise sperm production. e.g. tuberculous epididymitis.
• History of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
• For HIV infected participants any of the following:
• CD4+ count \<100 cells/μL
• Received intravenous antifungal medication within the last 90 days
• Participants with newly diagnosed tuberculosis and HIV that require initiation of appropriate HIV therapy before participants has received at least 2 weeks of an antituberculosis regimen.
• Received pretomanid and/or delamanid to treat TB
• Known chronic hepatitis B or C
• For HIV infected participants:
• The following antiretroviral therapy (ART) should not be used:

Sponsors & Collaborators

• Global Alliance for TB Drug Development: lead

Study Sites (4)

National Center for Tuberculosis and Lung Diseases

Tbilisi, Georgia

Location

CHRU, Sizwe Tropical Diseases Hospital

Johannesburg, South Africa

Location

Isango Lethemba TB Research Unit Empilweni TB Hospital

Port Elizabeth, South Africa

Location

The Aurum Institute: Rustenburg Clinical Research Centre

Rustenburg, South Africa

Location

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis, Multidrug-Resistant; Tuberculosis; Extensively Drug-Resistant Tuberculosis

Interventions

pretomanid; bedaquiline; Moxifloxacin; Pyrazinamide

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Antonio Lombardi
• Organization: TB Alliance

Antonio.Lombardi-Consultant@tballiance.org

917-601-0024

Study Officials

• Antonio Lombardi, MD

  Global Alliance for TB Drug Development

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Model Details: Phase 2 single arm multi-center, open-label clinical trial in DR-TB participants. Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg \+ moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks. Participants will be followed for 52 weeks after end of treatment

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: November 27, 2019
• Study Start: September 16, 2021
• Primary Completion: June 19, 2023
• Study Completion: July 17, 2024
• Last Updated: January 17, 2025
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Locations

ZA (3); GE (1)