A Phase 2 Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of Ethionamide Alone and in Combination With BVL-GSK098

• Status: Not yet recruiting
• Trial end date: 2023-10-01
• Target enrollment: 0
• Participant gender: All

Summary

To evaluate the 7-day early bactericidal activity (EBA), pharmacokinetics (PK), safety and tolerability of ethionamide (Eto) with or without BVL-GSK098 in participants with rifampicin- and isoniazid-susceptible pulmonary TB.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: TASK Applied Science
• Treatments: Ethionamide; Isoniazid

Criteria

Inclusion Criteria:

• Participants are required to meet all the following criteria in order to be randomized.

1. Provide written, informed consent prior to all trial-related procedures.

2. Male or female, aged between 18 and 65 years, inclusive.

3. Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.

4. Newly diagnosed and untreated pulmonary TB.

5. Rifampicin- and isoniazid-susceptible pulmonary TB as determined by molecular testing (GeneXpert XDR or Genotype MTBDRplus for INH).

6. A chest X-ray taken during the screening period or up to 2 weeks before screening which, in the opinion of the investigator, is consistent with TB.

7. GeneXpert positive with a quantitative readout of medium or high.

8. Ability to produce an adequate volume of sputum as estimated from an overnight sputum collection sample (estimated 10 ml or more).

9. Be of non-childbearing potential or using effective methods of birth control.

10. For WOCBP, injectable or other contraceptive methods (per Appendix 1) need to be given prior to or during screening, and at least 2 days prior to first dose of IP.

Exclusion Criteria:

• Participants will be excluded from participation if they fulfil any of the following criteria.

Medical History

11. Evidence of clinically significant conditions or findings, other than TB, that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator.

12. History of epilepsy, seizures or other neuropsychiatric disorders that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator

13. History of hypothyroidism

14. QTcF of >450 ms at baseline

15. Clinically significant evidence of extrathoracic TB, as judged by the investigator.

16. History of allergy to any of the trial IP as confirmed by the clinical judgement of the investigator.

17. Alcohol or drug abuse, that in the opinion of the investigator, is sufficient to compromise the safety or cooperation of the participant.

18. HIV positive AND:

1. CD4 < 250cells/mm3

2. OR, on ART in stage 1 only. Participants established on ART (2 NRTIs and dolutegravir) for more than 30 days at start of screening are eligible for participation in stage 2.

NOTE: ART permitted in Stage 2 is limited to the following in line with local guidelines for 1st line ART:

• NRTIs selected from: Emtricitabine, Lamivudine, Tenofovir

• PLUS Dolutegravir

As the drug-drug interaction potential of ART has not been fully investigated with the IP, NNRTIs (efavirenz, nevirapine) and other protease inhibitors will not be permitted in this study.

19. Female participant who is pregnant, breast-feeding, or planning to conceive a child within the anticipated period of trial participation. Male participant planning to conceive a child for at least 90 days, after the last dose of study intervention in the trial.

Treatment History

20. Participation in other clinical studies with investigational agents within 8 weeks prior to screening.

21. Treatment received for this episode of TB with any drug active against M.tb (including but not limited to isoniazid, ethambutol, amikacin, cycloserine, fluoroquinolones, rifabutin, rifampicin, streptomycin, kanamycin, para-aminosalicylic acid, rifapentine, pyrazinamide, thioacetazone, capreomycin, thioamides).

22. Treatment with immunosuppressive medications such as TNF-alpha inhibitors within 2 weeks prior to screening, or systemic corticosteroids for more than 7 days within 2 weeks prior to screening.