Actively Recruiting
A Phase 2 Randomized, Open-label Trial to Evaluate the Early Bactericidal Activity, Safety, Tolerability, and Dose-Response of Oral Alpibectir in Combination With Ethionamide, and With Ethionamide, Rifampicin, Pyrazinamide, and Ethambutol in Adults With Newly Diagnosed, Drug-Susceptible Pulmonary Tuberculosis
Led by TASK Applied Science · Updated on 2025-03-07
60
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
T
TASK Applied Science
Lead Sponsor
I
Innovative Medicines Initiative
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the early effects, safety, and dose-response of oral alpibectir combined with ethionamide and other standard tuberculosis drugs in adults with newly diagnosed, drug-susceptible pulmonary tuberculosis. This phase 2 randomized, open-label trial aims to optimize dosing and confirm safety for potential future use as an alternative treatment for isoniazid mono-resistant TB. The study also explores novel biomarkers from sputum and blood samples to improve treatment monitoring beyond traditional methods. The trial includes two sequential cohorts with participants randomly assigned to experimental treatment arms or a standard care control group. All treatments are oral and given once daily for 14 days. Cohort 1 focuses on safety and dose optimization of alpibectir with ethionamide at two dose levels. After an interim safety review, cohort 2 evaluates the safety of combining alpibectir and ethionamide with rifampicin, pyrazinamide, and ethambutol. Participants receive pyridoxine to prevent peripheral neuropathy, and those with HIV may continue selected antiretroviral therapies. Participants will be hospitalized and closely monitored throughout the treatment period, with continuous medical attention and safety assessments. The study measures early bactericidal activity over 14 days using microbiological and molecular tests, as well as pharmacokinetic analyses and biomarker evaluations from sputum and blood samples. Safety, tolerability, and potential drug interactions are carefully assessed to inform future clinical development. Total participation duration covers the 14-day treatment and observation period.
CONDITIONS
Brief Title
A Study of the Early Effects, Safety, and Acceptability of Oral Alpibectir in Combination With Ethionamide
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Provide written, informed consent and agree to follow all study procedures
- Male or female aged 18 to 65 years inclusive
- Body weight between 40 and 90 kg inclusive
- Newly diagnosed and untreated for current pulmonary TB episode
- Rifampicin- and isoniazid-susceptible pulmonary TB confirmed by molecular tests
- Chest X-ray consistent with TB taken during screening or within 2 weeks prior
- GeneXpert positive with medium or high quantitative readout
- Ability to produce 10 ml or more of sputum
- Non-childbearing potential or use effective birth control if of childbearing potential
- Female participants not using contraception agree to receive approved methods before treatment
- Male participants agree to refrain from semen donation and use condoms during and 90 days after treatment
You will not qualify if you...
- Clinically significant conditions other than TB affecting safety or trial interpretation
- Poor general health where treatment delay is unsafe
- History of epilepsy, seizures, or neuropsychiatric disorders impacting safety
- Cirrhosis or unstable liver/biliary disease
- History of hypothyroidism
- QTcF interval greater than 450 ms at baseline
- Evidence of extra-thoracic TB
- Allergy to any trial medication
- Alcohol or drug abuse compromising safety or cooperation
- HIV positive with CD4 count below 250 cells/mm3 or on disallowed ART regimens
- Female who is pregnant, breastfeeding, or planning pregnancy during and 90 days after study
- Participation in other investigational drug trials within 8 weeks
- Prior treatment for current TB episode with active TB drugs
- Use of immunosuppressive drugs recently
- Use of prohibited concomitant medications during study
- Positive hepatitis B surface antigen or hepatitis C antibody
- Abnormal laboratory values including kidney, liver, blood counts, thyroid, or glucose levels
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 14 days
Participants receive oral alpibectir in combination with ethionamide, and in some arms, rifampicin, pyrazinamide, and ethambutol to treat pulmonary tuberculosis. Treatment lasts 14 days with continuous medical monitoring in hospital.
Daily visits in hospital from admission through day 15
Duration - Up to 14 days following treatment
Participants are monitored for safety, tolerability, and treatment effects including biomarker assessments from sputum and blood samples after treatment ends.
Multiple visits for safety and biomarker assessments
Trial Site Locations
Total: 1 location
1
TASK
Cape Town, Western Cape, South Africa, 7550
Actively Recruiting
Research Team
G
Gifty Okyere-Manu, MBChB
V
Vani Govender, Masters Medical Science
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
5
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