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

Sponsor

Thirty Respiratory Limited (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06041919

Collaborator

(none)

Enrollment

Location

Arms

22.4

Anticipated Duration (Months)

3.4

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Rifampicin Susceptible Pulmonary Tuberculosis	Drug: RESP301 Drug: HRZE	Phase 2

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel control arm, randomised clinical study in two sequential stages, with no stratificationParallel control arm, randomised clinical study in two sequential stages, with no stratification

Masking:

Single (Outcomes Assessor)

Masking Description:

Microbiology staff will be blinded to treatment allocation.

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Sep 19, 2023

Anticipated Primary Completion Date :

Apr 30, 2024

Anticipated Study Completion Date :

Jul 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 (Active) Inhaled RESP301 6ml via nebulisation three times daily	Drug: RESP301 Nitric Oxide agent
Active Comparator: 2 (Control) HRZE taken orally once daily	Drug: HRZE isoniazid 75 mg (H), rifampicin 150 mg (R), pyrazinamide 400 mg (Z), ethambutol 275 mg (E)
Experimental: 3 (Active) Inhaled RESP301 6 ml via nebulisation once daily	Drug: RESP301 Nitric Oxide agent
Experimental: 4 (Active) Inhaled RESP301 6 ml via nebulisation twice daily	Drug: RESP301 Nitric Oxide agent
Experimental: 5 (Active) Inhaled RESP301 6 ml via nebulisation three times daily plus HRZE taken orally once dialy	Drug: RESP301 Nitric Oxide agent Drug: HRZE isoniazid 75 mg (H), rifampicin 150 mg (R), pyrazinamide 400 mg (Z), ethambutol 275 mg (E)

Outcome Measures

Primary Outcome Measures

To determine the Early Bactericidal Activity (EBA) of inhaled RESP301 [14 days]
Overnight sputum collection from which viable mycobacteria in the sample is quantified as time to positivity (TTP)

Secondary Outcome Measures

To determine the Early Bactericidal Activity (EBA) of inhaled RESP301 [14 days]
Overnight sputum collection from which viable mycobacteria in the sample is quantified as colony forming units (CFU)
To determine the safety and tolerability of inhaled RESP301 [2 months]
Incidence of Treatment Emergent Adverse Events (TEAEs) will be presented by severity, drug relatedness, seriousness, leading to early withdrawal and leading to death.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	TASK Clinical Research Centre	Cape Town	Bellville	South Africa	7531

Sponsors and Collaborators

Thirty Respiratory Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Thirty Respiratory Limited

ClinicalTrials.gov Identifier:

NCT06041919

Other Study ID Numbers:

RESP30X-EBA

First Posted:

Sep 18, 2023

Last Update Posted:

Sep 18, 2023

Last Verified:

Sep 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Thirty Respiratory Limited

Early Bactericidal Activity (EBA)

Additional relevant MeSH terms:

Tuberculosis

Tuberculosis, Pulmonary

Study Results

No Results Posted as of Sep 18, 2023