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Tuberculosis, PulmonaryPhase 2PaSEMNCT04179500

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

A Phase 2 study testing Pretomanid, Bedaquiline and moxifloxacin in people with Tuberculosis, Pulmonary and Tuberculosis, Multidrug-Resistant, run by Global Alliance for TB Drug Development at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Pretomanid, Bedaquiline and moxifloxacin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
4 sitesin 2 countries
Study dates
16 Sep 2021to 17 Jul 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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.
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  • 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:
  • 1. Stavudine 2. Zidovudine 3. Didanosine 4. Triple NRTI regimen is not considered optimal for HIV treatment (poor efficacy)
  • 13. Participants with the following toxicities at screening as defined by the enhanced Division of Microbiology and Infectious Disease (DMID) adult toxicity table (Draft November 2007) where applicable:
  • Platelets <75,000/mm3
  • Creatinine >1.5 times upper limit of normal (ULN)
  • eGFR ≤ 60 mL/min
  • Haemoglobin <8.0 g/dL
  • Serum potassium less than the lower limit of normal for the laboratory. This may be repeated once
  • AST:
  • ≥3.0 x ULN to be excluded
  • results between 1.5 x ULN and 3 x ULN must be discussed with and approved by the Sponsor Medical Monitor
  • ALT:
  • ≥3.0 x ULN to be excluded
  • greater than ULN must be discussed with and approved by the Sponsor Medical Monitor
  • ALP:
  • ≥3.0 x ULN to be excluded
  • 2.0 - <3.0 x ULN must be discussed with and approved by the Sponsor Medical Monitor
  • Total bilirubin:
  • >1.5 x ULN to be excluded
  • Greater than ULN must be discussed with and approved by the Sponsor Medical Monitor
  • Direct bilirubin:
  • greater than 1x ULN to be excluded
  • Positive hepatitis B surface Ag, or hepatitis C antibody

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

South Africa3 sites

  • CHRU, Sizwe Tropical Diseases Hospital

    Johannesburg

  • Isango Lethemba TB Research Unit Empilweni TB Hospital

    Port Elizabeth

  • The Aurum Institute: Rustenburg Clinical Research Centre

    Rustenburg

Other trials in South Africa

Georgia1 site

  • National Center for Tuberculosis and Lung Diseases

    Tbilisi

Other trials in Georgia

About this study

Official title: An Open-Label Phase 2 Trial to Evaluate the Male Reproductive Safety of a 6-Month Combination Treatment for Pulmonary Tuberculosis (TB) of Bedaquiline Plus Pretomanid Plus Moxifloxacin Plus Pyrazinamide (BPaMZ) in Adult Male Participants With Drug Resistant Pulmonary TB

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).

Read the detailed description

The primary objective of this study is to assess the male reproductive safety of pretomanid in the regimen (BPaMZ) of bedaquiline 200mg (200mg daily for 8 weeks then 100 mg daily for 18 weeks), together with pretomanid 200 mg (1x daily) + moxifloxacin 400 mg (1x daily) + pyrazinamide 1500 mg (1 x daily) for 26 weeks in participants with drug-resistant pulmonary tuberculosis (DR-TB).

The secondary objective of the study is to evaluate the tuberculosis (TB) treatment efficacy, safety and tolerability after 26 weeks of active treatment for TB and follow up until 52 weeks after end of the above-described treatment regimen in participants with DR-TB.

Being tested
Pretomanid, Bedaquiline, moxifloxacin, pyrazinamide
Keywords
tuberculosis, TB, DR-TB, pretomanid (PA), PA-824, XDR TB, Pa
Medical subject headings
Tuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Tuberculosis, Extensively Drug-Resistant Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PretomanidDrug

    Also called Pa-824, Doprevla, Pa

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

  • BedaquilineDrug

    Also called Sirturo, B

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

  • moxifloxacinDrug

    Also called Avelox, M

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

  • pyrazinamideDrug

    Also called Pyzina, Tebrazid, Z

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

Study groups in NCT04179500
Study groupRoleWhat they receive
Study ParticipantsExperimentalParticipants 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.
Receives: Drug: Pretomanid; Drug: Bedaquiline; Drug: moxifloxacin; Drug: pyrazinamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Week 26

Secondary outcomes (6)

  1. Change From Baseline in Total Sperm Count at 12 Weeks

    Change from baseline in total sperm number at 12 weeks of therapy. Total sperm count is calculated by multiplying the sperm cell concentration by the ejaculate volume.

    Measured: Baseline to Week 12

  2. Change From Baseline Total Sperm Count at 44 Weeks

    Change from baseline in total sperm number at 44 weeks (18 months post treatment completion). Total sperm count is calculated by multiplying the sperm cell concentration by the ejaculate volume.

    Measured: Baseline through 44 weeks

  3. Luteinizing Hormone (LH)

    (LH) at baseline, 26, 44, and 78 weeks.

    Measured: Baseline to Week 78

  4. FSH

    FSH at baseline, weeks 26, 44 and 78

    Measured: Baseline to week 78

  5. Testosterone

    testosterone level at baseline, 26, 44 and 78 weeks.

    Measured: Baseline to 78 weeks

  6. Inhibin B

    inhibin B at baseline, weeks 26, 44 and 78

    Measured: Baseline to 78 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Nov 2019
  2. Study start16 Sep 2021
  3. Primary completion19 Jun 2023
  4. Study completion17 Jul 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04179500
Sponsor's protocol ID
Pa-824-CL-012
Acronym
PaSEM
Status last verified
Sep 2024
First submitted
25 Nov 2019
Last updated
17 Jan 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pretomanid, Bedaquiline and moxifloxacin in people with Tuberculosis, Pulmonary and Tuberculosis, Multidrug-Resistant, run by Global Alliance for TB Drug Development at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in South Africa, Georgia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change Form Baseline Total Sperm Count (time frame: Week 26). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04179500.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2025.

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