Clinical trial NCT06041919: Evaluating the Early Bactericidal Activity, Safety and Tolerability of Nebulised RESP301 in Adults With Tuberculosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Rifampicin Susceptible Pulmonary Tuberculosis
Keywords: Early Bactericidal Activity (EBA)
Lead sponsor: Thirty Respiratory Limited
Sponsor class: INDUSTRY
First posted: 2023-09-18
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel control arm, randomised clinical study in two sequential stages, with no stratification
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Early Bactericidal Activity (EBA) of inhaled RESP301 measured as time to positivity (TTP)
timeFrame: 14 days
Secondary outcomes:
measure: Early Bactericidal Activity (EBA) of inhaled RESP301 measured as colony forming units (CFU)
timeFrame: 14 days
measure: Safety and tolerability of inhaled RESP301 measured as incidence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: 1.5 months
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: TASK Clinical Research Centre
state: Bellville
Study officials:
References: