Study of a Nebulised Nitric Oxide Generating Solution in Patients With Mycobacterium Abscessus (NOMAB)

Phase II Open Label Study of a Nebulised Nitric Oxide Generating Solution in Patients With Mycobacterium Abscessus Pulmonary Disease

• To evaluate the change in M. abscessus cfu/g in induced sputum samples from baseline to the end of treatment with RESP301 in patients with cystic fibrosis who have treatment-naïve or treatment-refractory M. abscessus-pulmonary disease
• To assess the safety and tolerability of RESP301 during treatment (28 days) and follow up (84 days) in patients with cystic fibrosis who have treatment naïve or treatment refractory M. abscessus-pulmonary disease

Study Overview

• Status: Active, not recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: RESP301

Detailed Description

Investigators will undertake an eighteen-week single centre, open label study in participants with cystic fibrosis infected with Mycobacterium abscessus (M. abscessus)-pulmonary disease (-PD).

The study will treat particpants with cystic fibrosis (CF) attending the Adult Cystic Fibrosis Centre at the Royal Papworth Hospital, Cambridge, United Kingdom. Participants will be consented and screened for the RESP301-003 study to enable approximately 12 participants to commence treatment with RESP301.

Participants will have M abscessus-PD as defined by the ATS/IDSA, specifically: (i) two or more positive sputum cultures for M. abscessus; (ii) radiological change consistent with NTM-PD; and (iii) symptoms consistent with NTM-PD, after exclusion of other causes.

Participants will be recruited who (1) have not commenced antibiotic treatment for M. abscessus-PD or (2) have treatment refractory M. abscessus-PD (defined as remaining sputum culture positive after 6 months or more of treatment). Treatment-refractory participants will be suitable for enrolment in the study if date of first dosing is at least 2 months since a change in M. abscessus treatment (or 4 months since change of Clofazimine).

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sarah Fielding; Phone Number: 01223 639719; Email: sarah.fielding2@nhs.net
• Study Contact Backup: Name: Victoria Hughes; Phone Number: 01223639678; Email: victoria.hughes1@nhs.net

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB30AY
      • Royal Papworth Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult patients of ≥18 years at time of informed consent
2. Patients with a clinical diagnosis of CF and confirmed by genetic testing
3. Diagnosis of treatment naïve or treatment refractory M. abscessus-PD
4. Signed informed consent documentation (indicating an understanding of the purpose and a willingness to meet the requirements for participation in the study)

Exclusion Criteria:

1. FEV1 <40% predicted
2. Methaemoglobin concentration > 2%
3. Use of nitric oxide donor medications such as prilocaine, sodium nitroprusside, and nitroglycerine within 30 days of proposed first treatment
4. Use of phosphodiesterase inhibitors (e.g., sildenafil) within 30 days of proposed first treatment
5. Evidence of pulmonary hypertension
6. History of frequent low volume or massive haemoptysis
7. Liver disease (i.e. liver cirrhosis, portal hypertension)
8. Subjects who have undergone organ transplantation
9. Pregnancy or lactation (female participants only)
10. Subjects who will not use appropriate forms of contraception for the duration of the study
11. Contraindication or unable to complete lung function testing
12. Contraindication or unable to tolerate nebulised hypertonic saline
13. Changes to previous NTM antibiotic regimen within two months of first dose of study treatment (or 4 months for clofazimine)
14. Subject has received investigational treatment as part of another interventional clinical trial within two months of the proposed first day of treatment
15. Required antibiotic treatment for a pulmonary exacerbation within 2 weeks of enrolment to the study.
16. Inability to undergo study related activities and / or commitments
17. Any subject who in the opinion of the investigator would not be best served by participating in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional; Single arm trial involving all patients receiving IMP	Drug: RESP301; Inhaled IMP delivered via nebulisation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mycobacterial load in induced sputum samples	The primary efficacy endpoint is the change in mycobacterial load in induced sputum samples as assessed by log10 change in M. abscessus cfu/g sputum from Baseline to End of Treatment.	Through study completion, average one year
Safety and tolerability	Safety and tolerability will be assessed by clinical safety laboratory measurements, physical examinations, vital signs, concomitant medications; cumulative incidence of adverse events (AEs), serious adverse events (SAEs) and severe AEs.	Through study completion, average one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mycobacterial load in spontaneously expectorated daily sputum samples	The change in mycobacterial load in spontaneously expectorated daily sputum samples from Baseline to Final Week of Treatment. For this secondary endpoint, Baseline is defined as the average M. abscessus cfu/g sputum in samples from the mornings of Days -14 to -1 inclusive. The final seven days of treatment are days 22 to 28 inclusive; the sputum samples are produced on the following mornings	Through study completion, average one year
Proportion of individuals achieving a ≥2 log10 decrease in the mycobacterial load - induced samples	Proportion of individuals achieving a ≥2 log10 decrease in the mycobacterial load as assessed by change in M. abscessus cfu/g in the induced sputum samples from Baseline to End of Treatment.	Through study completion, average one year
Proportion of individuals achieving a ≥2 log10 decrease in the mycobacterial load - spontaneous samples	Proportion of individuals achieving a ≥2 log10 decrease in the mycobacterial load as assessed by change in M. abscessus cfu/g in the spontaneously expectorated sputum samples from Baseline to Final Week of Treatment.	Through study completion, average one year

Collaborators and Investigators

• Sponsor: Papworth Hospital NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: September 13, 2021
• First Submitted That Met QC Criteria: October 21, 2021
• First Posted (Actual): November 1, 2021

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Mycobacterium abscessus
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Pancreatic Diseases; Mycobacterium Infections; Cystic Fibrosis
• Other Study ID Numbers: P02702

Drug and device information, study documents

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