Clinical trial NCT05101915: Study of a Nebulised Nitric Oxide Generating Solution in Patients With Mycobacterium Abscessus
Official title: Phase II Open Label Study of a Nebulised Nitric Oxide Generating Solution in Patients With Mycobacterium Abscessus Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Mycobacterium abscessus
Lead sponsor: Papworth Hospital NHS Foundation Trust
Sponsor class: OTHER_GOV
First posted: 2021-11-01
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a single centre, non-randomized, open label study
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Mycobacterial load in induced sputum samples
timeFrame: Through study completion, average one year
measure: Safety and tolerability
timeFrame: Through study completion, average one year
Secondary outcomes:
measure: Change in mycobacterial load in spontaneously expectorated daily sputum samples
timeFrame: Through study completion, average one year
measure: Proportion of individuals achieving a ≥2 log10 decrease in the mycobacterial load - induced samples
timeFrame: Through study completion, average one year
measure: Proportion of individuals achieving a ≥2 log10 decrease in the mycobacterial load - spontaneous samples
timeFrame: Through study completion, average one year
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital NHS Foundation Trust
state: Cambridgeshire
Study officials:
References: