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

Primary Purpose

Cystic Fibrosis

Status

Active

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

RESP301

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Mycobacterium abscessus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Royal Papworth Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Interventional

Arm Description

Single arm trial involving all patients receiving IMP

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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

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.

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.

Full Information

NCT ID

NCT05101915

First Posted

September 13, 2021

Last Updated

July 12, 2023

Sponsor

Papworth Hospital NHS Foundation Trust

1. Study Identification

Unique Protocol Identification Number

NCT05101915

Brief Title

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

Acronym

NOMAB

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

November 1, 2021 (Actual)

Primary Completion Date

October 1, 2024 (Anticipated)

Study Completion Date

October 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Papworth Hospital NHS Foundation Trust

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis

Keywords

Mycobacterium abscessus

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

This is a single centre, non-randomized, open label study

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Interventional

Arm Type

Experimental

Arm Description

Single arm trial involving all patients receiving IMP

Intervention Type

Drug

Intervention Name(s)

RESP301

Intervention Description

Inhaled IMP delivered via nebulisation

Primary Outcome Measure Information:

Title

Mycobacterial load in induced sputum samples

Description

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.

Time Frame