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

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Rifampicin Susceptible Pulmonary Tuberculosis
• Intervention / Treatment: Drug: RESP301; Drug: HRZE

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 Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Inva Hoti, PhD; Phone Number: +44 (0) 1235 431 201; Email: inva.hoti@30.technology

Study Locations

• South Africa
  • Bellville
    • Cape Town, Bellville, South Africa, 7531
      • TASK Clinical Research Centre
      • Contact: Lee-Ann Davids, MD; Phone Number: +27 21 917 1044; Email: dr.lee-ann@task.org.za
      • Principal Investigator: Lee-Ann Davids, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Thirty Respiratory Limited

Study record dates

Study Major Dates

• Study Start (Estimated): September 19, 2023
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): July 31, 2025

Study Registration Dates

• First Submitted: August 21, 2023
• First Submitted That Met QC Criteria: September 11, 2023
• First Posted (Actual): September 18, 2023

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Early Bactericidal Activity (EBA)
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary
• Other Study ID Numbers: RESP30X-EBA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: To be determined

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No