Decision was made by the sponsor not to progress to Stage 2

A Phase 2, Single-Centre, Open-Label, Parallel Control Arm, Randomised Clinical Study to Evaluate the Early Bactericidal Activity (EBA), Safety and Tolerability of Nebulised RESP301 in Adults with Newly Diagnosed, Rifampicin Susceptible Pulmonary Tuberculosis

A total of approximately 15 participants will be recruited per treatment arm (total of approximately 75 participants in the study). Control arm participants will be split across sequential stages stages 1 and 2, with no stratification.

Stage 1: To determine the EBA of

• Treatment Arm 1 (Active; n = 15) - inhaled RESP301 6 ml dosed via nebulisation administered three times daily over 14 days
• Treatment Arm 2 (Control; n= 5) - HRZE taken orally once daily

On completion of Stage 1, recruitment will be paused and an interim analysis performed to determine whether the study should proceed to Stage 2.

Stage 2: To determine the EBA of

• Treatment Arm 2 (Control; n= 10) - HRZE taken orally once daily
• Treatment Arm 3 (Active; n = 15) - inhaled RESP301 6 ml dosed via nebulisation administered once daily over 14 days
• Treatment Arm 4 (Active; n = 15) - inhaled RESP301 6 ml dosed via nebulisation administered twice daily over 14 days
• Treatment Arm 5 (Active; n = 15) - inhaled RESP301 6 ml dosed via nebulisation administered three times daily in combination with HRZE taken orally once daily over 14 days

Inclusion Criteria:

• Provide written, informed consent prior to all study-related procedures and agree to undergo all study procedures
• Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive
• Newly diagnosed pulmonary TB
• Rifampicin susceptible pulmonary TB as determined by molecular testing
• Ability to produce an adequate volume of sputum as estimated from a pre-treatment overnight sputum collection sample (estimated 10 ml or more)
• Spirometry performed during screening with a FEV1 of ≥ 40%
• Be of non-childbearing potential or willing to use effective methods of contraception

Exclusion Criteria:

• HIV positive AND CD4 < 350 cells/mm3 OR are receiving antiviral therapy (ART)
• Methaemoglobin saturation (SpMet) >3%
• Female participant who is pregnant or breast-feeding
• Participants planning to conceive a child within the anticipated period of study participation and for at least 90 days after the last dose of IMP in the 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
• 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.
• Treatment with nitric oxide and other nitric oxide donor agents, phosphodiesterase inhibitors and lung surfactant drugs, within 30 days prior to screening

IPD is confidential until the CSR is published

participants who received at least one dose of RESP301 or HRZE

Stage 1: Dosing period 14 days + Follow-up period 14 days. Stage 2: Participants did not enter the treatment phase due to early study termination

Stage 2 (Arm 3,4, and 5): Participants did not enter the treatment phase due to early study termination

Microbiology staff will be blinded to treatment allocation.