A Phase 2 Study to Evaluate the Early Bactericidal Activity, Safety and Tolerability of Nebulised RESP301 in Adults With Newly Diagnosed, Rifampicin Susceptible Pulmonary Tuberculosis
Overview
- Phase
- Phase 2
- Intervention
- RESP301
- Conditions
- Rifampicin Susceptible Pulmonary Tuberculosis
- Sponsor
- Thirty Respiratory Limited
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Early Bactericidal Activity (EBA) of Inhaled RESP301 Measured as Time to Positivity (TTP)
- Status
- Terminated
- Last Updated
- 9 months ago
Overview
Brief Summary
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
Detailed Description
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
Investigators
Eligibility Criteria
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
Arms & Interventions
1 (Active)
Inhaled RESP301 6ml via nebulisation three times daily
Intervention: RESP301
2 (Control)
HRZE taken orally once daily
Intervention: HRZE
3 (Active)
Inhaled RESP301 6 ml via nebulisation once daily
Intervention: RESP301
4 (Active)
Inhaled RESP301 6 ml via nebulisation twice daily
Intervention: RESP301
5 (Active)
Inhaled RESP301 6 ml via nebulisation three times daily plus HRZE taken orally once dialy
Intervention: RESP301
5 (Active)
Inhaled RESP301 6 ml via nebulisation three times daily plus HRZE taken orally once dialy
Intervention: HRZE
Outcomes
Primary Outcomes
Early Bactericidal Activity (EBA) of Inhaled RESP301 Measured as Time to Positivity (TTP)
Time Frame: 0-2, 0-7, 0-14, 0-15 and 14-15 days
Overnight sputum collection from which viable mycobacteria in the sample is quantified as TTP Observed EBA for 0-2, 0-7, 0-14, 0-15 and 14-15 days in TTP (hours) for treatment in each of the treatment groups
Secondary Outcomes
- Early Bactericidal Activity (EBA) of Inhaled RESP301 Measured as Colony Forming Units (CFU)(0-2, 0-7, 0-14, 0-15 and 14-15 days)
- Safety and Tolerability of Inhaled RESP301 Measured as Number of Treatment Emergent Adverse Events (TEAEs)(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)