A Phase 2 Trial to Evaluate the EBA, Safety and Tolerability of Eto Alone and in Combination With BVL-GSK098

Korábbi kezelés

• Alcohol or drug abuse, that in the opinion of the investigator, is sufficient to compromise the safety or cooperation of the participant.
• 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.
• Participation in other clinical studies with investigational agents within 8 weeks prior to screening.
• 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).
• 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.

Más betegség

• 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.
• History of epilepsy, seizures or other neuropsychiatric disorders that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator
• History of hypothyroidism
• History of allergy to any of the trial IP as confirmed by the clinical judgement of the investigator.
• HIV positive AND:

Egyéb

• Participants will be excluded from participation if they fulfil any of the following criteria.
  • Medical History
• QTcF of >450 ms at baseline
• Clinically significant evidence of extrathoracic TB, as judged by the investigator.
• CD4 < 250cells/mm3
• 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
• 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

• Participants are required to meet all the following criteria in order to be randomized.
• Provide written, informed consent prior to all trial-related procedures.
• Male or female, aged between 18 and 65 years, inclusive.
• Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
• Newly diagnosed and untreated pulmonary TB.
• Rifampicin- and isoniazid-susceptible pulmonary TB as determined by molecular testing (GeneXpert XDR or Genotype MTBDRplus for INH).
• 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.
• GeneXpert positive with a quantitative readout of medium or high.
• Ability to produce an adequate volume of sputum as estimated from an overnight sputum collection sample (estimated 10 ml or more).
• Be of non-childbearing potential or using effective methods of birth control.
• 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.