Nebulised nitric oxide generating liquid in patients with CF
Research type
Research Study
Full title
Phase II open label study of a nebulised nitric oxide generating solution in patients with cystic fibrosis
IRAS ID
287232
Contact name
Charles Haworth
Contact email
Sponsor organisation
Royal Papworth Hospital NHS Foundation Trust
Eudract number
2020-003409-71
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 6 months, 29 days
Research summary
The purpose of this study is to assess the efficacy, safety and tolerability of RESP301, a nebulised nitric oxide generating solution in patients with cystic fibrosis (CF) and Mycobacterium abscessus-pulmonary disease.
The prevalence of Mycobacterium abscessus lung infection is increasing in people with cystic fibrosis and it is particularly difficult to treat because M. abscessus is resistant to most antibiotics, the treatment often lasts for more than 18 months, and the treatment is often associated with significant side effects.
Laboratory based studies show that nitric oxide is very effective at killing M. abscessus and other bacteria such as Pseudomonas aeruginosa. RESP301 is a nebulised liquid that is administered three time a day and releases nitric oxide within the lungs.
While nitric oxide (NO) is already marketed in the US to treat other lung conditions, RESP301 has potential advantages over directly inhaled NO gas as it is administered through a nebuliser three times a day rather than continuously, it results in higher concentrations of NO at the site of infection, and the specific formulation of RESP301 ensures minimal production of nitrogen dioxide.In this 126 day (18 week) study (14-day lead-in period, 28-day treatment with RESP301 and 84 days follow-on observation) we will assess the efficacy, safety, and tolerability of RESP301 in 12 patients with cystic fibrosis and M. abscessus-pulmonary disease attending the Adult CF Centre at Royal Papworth Hospital in Cambridge.
Lay Summary of Results
NOMab Trial Results Summary for Regulatory Agencies and Public Access
Who carried out the research?
The study was performed at Royal Papworth Hospital in Cambridge, UK between 21st November 2021 and 1st January 2024. Royal Papworth Hospital sponsored the study and 30 Technology funded the study.
Why was the research needed?
Mycobacterium abscessus is a bacterium (bug) that can infect the lungs of people with cystic fibrosis and bronchiectasis, and in some circumstances the lungs of people who have had lung transplants. Treatment of this infection is difficult because Mycobacterium abscessus is resistant to most types of antibiotics and for this reason, current treatment approaches often involve the administration of intravenous antibiotics for several weeks in combination with
oral and inhaled antibiotics for several months. RESP301 is a nitric oxide generating treatment which has been shown to kill mycobacterium abscessus very effectively in laboratory experiments.
The main question to be answered by the study was: does inhaling RESP301 three times daily through a nebuliser reduce the amount of Mycobacterium abscessus infection in patients with cystic fibrosis, bronchiectasis or lung transplant recipients?Who participated in the study?
Six people with Mycobacterium abscessus related lung disease participated in the study. Three of the participants had cystic fibrosis and three had bronchiectasis. No lung transplant recipients were recruited.
What treatments did the participants receive?
Clinical Trials.gov ID: NCT05101915 MHRA CTA 21440/0212/001
NOMab Trial Results SummaryEach participant initially received a half dose of RESP301 (administered through an eFlow nebuliser system) at Royal Papworth Hospital to check that they tolerated the inhaled medicine without difficulty. If the initial dose was tolerated, participants then received three full doses of RESP301 while at Royal Papworth Hospital (two on the initial day of dosing and one the next morning) before being discharged to take the medication at home 3 times a day for a total of 28 days. Participants were reviewed once a week at Royal Papworth Hospital during the 28-day dosing period and performed home monitoring of lung function, weight, oxygen saturations and symptoms, the results of which were visible to the study team.
What medical problems (adverse reactions) did the participants have?
A total of 67 adverse events (potential side effects) were reported during the study, with 5 classified as definitely related, 7 probably related and 15 possibly related to RESP301. The remaining 40 events were deemed to unrelated to the RESP301. The side effects definitely
related to RESP301 were bronchospasm (a tight and wheezy chest associated with a temporary reduction in lung function), chest discomfort, cough, altered taste, and breathlessness. One of the six participants developed bronchospasm after the initial half test
dose and so did not continue with study treatment.What were the results of the study?
The main outcome measure for the study was the change in the amount of Mycobacterium abscessus found in induced sputum samples between the beginning and end of the treatment period with RESP301. Induced sputum samples are samples collected during and after nebulising 7% hypertonic saline. Three participants had a notable reduction in the amount of Mycobacterium abscessus between the start and the end of treatment. The other participant
had a marginal increase. One participant had negative cultures at the start of treatment and so change in the amount of Mycobacterium abscessus could not be evaluated. Secondary outcome measures for the study included changes in the amount of Mycobacterium abscessus in sputum samples spontaneously coughed up on a daily basis at home (without nebulising 7% hypertonic saline), changes in how quickly MycobacteriumClinical Trials.gov ID: NCT05101915 MHRA CTA 21440/0212/001
NOMab Trial Results Summaryabscessus grew in sputum cultures, and changes in symptoms between the start and end of treatment with RESP301.
Four of the participants showed a small reduction in the amount of Mycobacterium abscessus in the daily collected sputum samples between baseline and the final week of treatment, while the other participant showed growth a slight increase. Overall, there was no significant change in average amount of Mycobacterium abscessus in the daily collected sputum samples between the start and end of treatment with RESP301. There was a statistically significant reduction in the rate of growth of Mycobacterium abscessus in the daily collected sputum cultures between the start and end of treatment, perhaps suggesting that RESP301 was hindering the growth of the bacteria causing the infection.How has this research helped patients and researchers?
This research has evaluated a new treatment approach for people with Mycobacterium abscessus lung infection. The results suggest that RESP301 may hinder the growth of the infection. In terms of side effects, RESP301 was safe and generally well tolerated however the
increased frequency of coughing and the episode of bronchospasm after the initial half dose. in one participant indicate a potential tolerability concern. Overall, RESP301 shows potential
for continued development and refinement.REC name
South West - Central Bristol Research Ethics Committee
REC reference
21/SW/0009
Date of REC Opinion
10 Mar 2021
REC opinion
Further Information Favourable Opinion