Evaluating the Early Bactericidal Activity, Safety and Tolerability of Nebulised RESP301 in Adults With Tuberculosis

NCT ID: NCT06041919

Last Updated: 2025-07-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-27
• Study Completion Date: 2025-03-06

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

Conditions

Rifampicin Susceptible Pulmonary Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

1 (Active)

Inhaled RESP301 6ml via nebulisation three times daily

Group Type: EXPERIMENTAL

RESP301

Intervention Type: DRUG

Nitric Oxide agent

2 (Control)

HRZE taken orally once daily

Group Type: ACTIVE_COMPARATOR

HRZE

Intervention Type: DRUG

isoniazid 75 mg (H), rifampicin 150 mg (R), pyrazinamide 400 mg (Z), ethambutol 275 mg (E)

3 (Active)

Inhaled RESP301 6 ml via nebulisation once daily

Group Type: EXPERIMENTAL

RESP301

Intervention Type: DRUG

Nitric Oxide agent

4 (Active)

Inhaled RESP301 6 ml via nebulisation twice daily

Group Type: EXPERIMENTAL

RESP301

Intervention Type: DRUG

Nitric Oxide agent

5 (Active)

Inhaled RESP301 6 ml via nebulisation three times daily plus HRZE taken orally once dialy

Group Type: EXPERIMENTAL

RESP301

Intervention Type: DRUG

Nitric Oxide agent

HRZE

Intervention Type: DRUG

isoniazid 75 mg (H), rifampicin 150 mg (R), pyrazinamide 400 mg (Z), ethambutol 275 mg (E)

Interventions

RESP301

Nitric Oxide agent

Intervention Type: DRUG

HRZE

isoniazid 75 mg (H), rifampicin 150 mg (R), pyrazinamide 400 mg (Z), ethambutol 275 mg (E)

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thirty Respiratory Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

TASK Clinical Research Centre

Cape Town, Bellville, South Africa

Countries

South Africa

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RESP30X-EBA

Identifier Type: -

Identifier Source: org_study_id