Clinical trial NCT04858451: COmmunity Patients at Risk of Viral Infections Including SARS-CoV-2
Official title: Community Participants With COPD or Bronchiectasis and at Risk of Respiratory Viral Infections Including SARS-CoV-2: An Open-label, Multicentre Feasibility Study of an Inhaled Nitric Oxide Generating Solution (RESP301)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COPD
Bronchiectasis
Lead sponsor: Thirty Respiratory Limited
Sponsor class: INDUSTRY
First posted: 2021-04-26
Enrollment: 88
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Part 1a: Dose Finding Phase

Up to 48 eligible participants will be administered single ascending doses of RESP301 to determine the maximum tolerated dose, according to the following schedule:

* 8 participants to receive RESP301 at a dose of 1 ml
* 8 participants to receive RESP301 at a dose of 2 ml
* 8 participants to receive RESP301 at a dose of 3 ml
* 8 participants to receive RESP301 at a dose of 4 ml
* 8 participants to receive RESP301 at a dose of 5 ml
* 8 participants to receive RESP301 at a dose of 6 ml

Part 1b: Concomitant Medication Expansion Phase

• 8 participants to receive RESP301 at MTD with short-acting bronchodilator administered 10min prior to RESP301

Part 2: Expansion Phase

A minimum of 150 patients will be enrolled in to the Expansion Phase. These may include eligible participants from Part 1.
Primary purpose: OTHER

Brief summary: Patients with a respiratory disease are at higher risk of poor outcomes due to worsening of symptoms caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and other respiratory infections. New therapies are needed for treating high risk patients at early stages of an infection. This study will assess the safety, tolerability and feasibility of using an inhaled nitric oxide generating solution, RESP301, as a self-administered treatment following flare-up of symptoms.

RESP301 is a liquid solution which produces nitric oxide in the lungs when inhaled using a nebuliser. The components of RESP301 are already used in clinical practice and inhaled nitric oxide is used as a treatment for newborns and patients with Chronic Obstructive Pulmonary Disease (COPD). In a laboratory setting, RESP301 has been shown to be effective against respiratory viruses, including SARS-CoV-2.

This study will first determine the maximum tolerated dose of RESP301 in up to 48 adult patients with COPD or bronchiectasis in the United Kingdom (UK) (Part 1a; Dose Finding Phase). Once the Maximum Tolerated Dose (MTD) has been determined in Part 1a, a cohort of 8 patients will be recruited and RESP301 administered at the MTD but these patients will in addition receive a single dose of a short acting bronchodilator 10 minutes preceding administration of RESP301.

After completion of Part 1, approximately 150 patients will be recruited into Part 2 of the trial (Expansion Phase). A minimum of 50 participants will receive a test dose of RESP301 during a screening visit. Response to the test dose will be monitored. Participants who tolerate the test dose will continue in the study and should contact the study team if they experience exacerbation symptoms in the next 52 weeks. Following a call with the site team to discuss symptoms, participants will receive RESP301 delivered to their home to self-administer for 7 days. The study duration for each participant will be at most 57 weeks, including the study visit and monthly calls. Participants who start the course of study treatment, will receive daily calls during the treatment period and will also be followed up after they complete the treatment.


Eligibility criteria: Inclusion Criteria:

1. Female of non-childbearing potential or male ≥35 years of age, at the time of signing the informed consent
2. Able and willing to provide informed consent
3. Spirometry-confirmed diagnosis of COPD (FEV1/FVC\<0.7 post-bronchodilator) or computerised tomography (CT) proven bronchiectasis
4. Part 1 only: FEV1 ≥50% predicted at screen 1 (i.e. FEV1 prior to any in-clinic administered short acting bronchodilator)

Exclusion Criteria:

1. Unable to safely use a nebuliser as required by the study according to Investigator's opinion
2. Severe COPD or bronchiectasis defined as FEV1 \<20% or requiring non-invasive ventilation
3. History of methaemoglobinaemia
4. Baseline methaemoglobin concentration (using fingertip sensor) \> 2%
5. Uncontrolled or severe asthma or history of severe bronchospasm
6. Presence of tracheostomy/inability to provide spirometry or contraindication for performing spirometry
7. Allergy to any of the components of the study intervention
8. Participation in other clinical investigations utilising investigational treatment within the last 30 days / 5 half lives whichever is longer
9. Deemed unlikely to be able to adhere to protocol in view of investigator
10. Any subject who in the opinion of the investigator would not be best served by participating in this clinical trial
11. Any unstable, uncontrolled or severe medical condition which in the opinion of the investigator would make the patient unsuitable for the trial
12. Participant lives at home with no other adults in the household (Part 2 only)
13. On long-term non-invasive ventilation and/or at higher risk of bronchospasm
14. Prescribed Nitric Oxide donating agent (Nitroprusside, Isosorbide dinitrate, Isosorbide mononitrate, Naproxcinod, Molsidomine and Linsidomine)
15. Female of childbearing potential
16. Clinical diagnosis of COPD but Screening Visit spirometry at study centre excludes COPD (i.e. FEV1/FVC post bronchodilator ratio is not \<0.7)

Primary outcomes:
measure: Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1
timeFrame: Screening Visit
measure: Feasibility of Self-administering RESP301 Treatment in Terms of Commencing Treatment
timeFrame: 1 day
measure: Feasibility of Self-administering RESP301 Treatment in Terms of Treatment Compliance
timeFrame: 7 days
Secondary outcomes:
measure: Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2)
timeFrame: Screening Visit
measure: Safety of RESP301 in Terms of Treatment Emergent Adverse Events
timeFrame: Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination)
measure: Safety of RESP301 in Terms of Serious Adverse Events
timeFrame: Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination)
measure: Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions
timeFrame: Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination)
measure: Safety of RESP301 in Terms of Treatment-related AEs
timeFrame: Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination)
measure: Efficacy of RESP301 in Terms of Percentage of Patients Recovered by Day 7
timeFrame: 7 days
measure: Efficacy of RESP301 in Terms of Percentage of Patients Recovered by Day 14
timeFrame: 7 days
measure: Efficacy of RESP301 in Terms of Time to Recovery
timeFrame: 21 days
measure: Efficacy of RESP301 in Terms of Preventing Exacerbation-related Hospitalisation and/or Death
timeFrame: 7 days
measure: Efficacy of RESP301 in Terms of Patient-reported Symptoms
timeFrame: 7 days
measure: Feasibility of Self-administering RESP301 Treatment in Terms of Receiving Treatment
timeFrame: 2 days
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust
Study officials:
References: