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

Primary Purpose

Rifampicin Susceptible Pulmonary Tuberculosis

Status
Recruiting
Phase
Phase 2
Locations
South Africa
Study Type
Interventional
Intervention
RESP301
HRZE
Sponsored by
Thirty Respiratory Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rifampicin Susceptible Pulmonary Tuberculosis focused on measuring Early Bactericidal Activity (EBA)

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • TASK Clinical Research CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Active Comparator

Experimental

Experimental

Experimental

Arm Label

1 (Active)

2 (Control)

3 (Active)

4 (Active)

5 (Active)

Arm Description

Inhaled RESP301 6ml via nebulisation three times daily

HRZE taken orally once daily

Inhaled RESP301 6 ml via nebulisation once daily

Inhaled RESP301 6 ml via nebulisation twice daily

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

Outcomes

Primary Outcome Measures

Early Bactericidal Activity (EBA) of inhaled RESP301 measured as time to positivity (TTP)
Overnight sputum collection from which viable mycobacteria in the sample is quantified as TTP

Secondary Outcome Measures

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

Full Information

First Posted
August 21, 2023
Last Updated
October 9, 2023
Sponsor
Thirty Respiratory Limited
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1. Study Identification

Unique Protocol Identification Number
NCT06041919
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 27, 2023 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
July 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Thirty Respiratory Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rifampicin Susceptible Pulmonary Tuberculosis
Keywords
Early Bactericidal Activity (EBA)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Parallel control arm, randomised clinical study in two sequential stages, with no stratification
Masking
Outcomes Assessor
Masking Description
Microbiology staff will be blinded to treatment allocation.
Allocation
Randomized
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1 (Active)
Arm Type
Experimental
Arm Description
Inhaled RESP301 6ml via nebulisation three times daily
Arm Title
2 (Control)
Arm Type
Active Comparator
Arm Description
HRZE taken orally once daily
Arm Title
3 (Active)
Arm Type
Experimental
Arm Description
Inhaled RESP301 6 ml via nebulisation once daily
Arm Title
4 (Active)
Arm Type
Experimental
Arm Description
Inhaled RESP301 6 ml via nebulisation twice daily
Arm Title
5 (Active)
Arm Type
Experimental
Arm Description
Inhaled RESP301 6 ml via nebulisation three times daily plus HRZE taken orally once dialy
Intervention Type
Drug
Intervention Name(s)
RESP301
Intervention Description
Nitric Oxide agent
Intervention Type
Drug
Intervention Name(s)
HRZE
Intervention Description
isoniazid 75 mg (H), rifampicin 150 mg (R), pyrazinamide 400 mg (Z), ethambutol 275 mg (E)
Primary Outcome Measure Information:
Title
Early Bactericidal Activity (EBA) of inhaled RESP301 measured as time to positivity (TTP)
Description
Overnight sputum collection from which viable mycobacteria in the sample is quantified as TTP
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Early Bactericidal Activity (EBA) of inhaled RESP301 measured as colony forming units (CFU)
Description
Overnight sputum collection from which viable mycobacteria in the sample is quantified as CFU
Time Frame
14 days
Title
Safety and tolerability of inhaled RESP301 measured as incidence of Treatment Emergent Adverse Events (TEAEs)
Description
Incidence of Treatment Emergent Adverse Events (TEAEs) will be presented by severity, drug relatedness, seriousness, leading to early withdrawal and leading to death.
Time Frame
1.5 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Inva Hoti, PhD
Phone
+44 (0) 1235 431 201
Email
inva.hoti@30.technology
Facility Information:
Facility Name
TASK Clinical Research Centre
City
Cape Town
State/Province
Bellville
ZIP/Postal Code
7531
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Veronique De Jager, MD
Phone
+27 21 100 3606
Email
dr.veronique@task.org.za
First Name & Middle Initial & Last Name & Degree
Veronique De Jager, MD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
IPD is confidential until the CSR is published

Learn more about this trial

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

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