COmmunity Patients at Risk of Viral Infections Including SARS-CoV-2

NCT ID: NCT04858451

Last Updated: 2025-01-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2023-02-08

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.

Conditions

COPD; Bronchiectasis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

All participants

In Part 1a, up to 48 patients will be administered single ascending doses of RESP301 (1-6ml; 8 patients per dose cohort). Provided that individual stopping criteria are not met in ≥3 participants, and there are no serious adverse events that are at least possibly related to RESP301, the next dose cohort can be enrolled. Patients can be enrolled into more than one dose cohort provided they did not meet individual stopping criteria.

In Part 1b, 8 participants will receive RESP301 at MTD determined in Part 1a, with short-acting bronchodilator administered 10min prior to RESP301.

In Part 2, a minimum of 150 patients will be enrolled. This may include patients who took part in Part 1. At least the first 50 patients will receive a test dose of RESP301 before enrolment into the "dormant phase". Patients who experience flare-up symptoms while in the dormant phase, may proceed to the treatment phase where they will self-administer RESP301 at home for 7 days.

Group Type: EXPERIMENTAL

RESP301

Intervention Type: DRUG

A single RESP301 dose administered at a study site to assess tolerability.

In patients who experience a flare-up during the study period, self-administered RESP301 treatment for 7 days, 3 times a day.

Interventions

RESP301

A single RESP301 dose administered at a study site to assess tolerability.

In patients who experience a flare-up during the study period, self-administered RESP301 treatment for 7 days, 3 times a day.

Intervention Type: DRUG

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)

• Minimum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thirty Respiratory Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Medicines Evaluation Unit

Manchester, , United Kingdom

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RESP301-005

Identifier Type: -

Identifier Source: org_study_id