NCT04858451: CORVIS

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

Terminated Phase 2 Results posted Last updated 31 January 2025

What this trial tests

Phase 2 trial testing RESP301 in COPD in 88 participants. Terminated before completion.

Timeline

1 March 2021

Primary endpoint
22 December 2022

8 February 2023

Quick facts

Lead sponsor	Thirty Respiratory Limited
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	other
Enrollment	88
Start date	1 March 2021
Primary completion	22 December 2022
Estimated completion	8 February 2023
Sites	2 locations across United Kingdom

Drugs / interventions tested

• RESP301 — full drug profile →

Conditions studied

• COPD — all drugs for COPD →
• Bronchiectasis — all drugs for Bronchiectasis →

Sponsor

Thirty Respiratory Limited — full company profile →

Who can join

35 and older, any sex, with COPD or Bronchiectasis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1 Primary · Screening Visit

Defined as percentage of participants able to tolerate the test dose, i.e. able to complete the test dose without any of the following: * Troublesome cough, chest pain or tightness, bronchospasm or dyspnoea that is deemed unacceptable by the patient * methaemoglobin \>5% during or \>3% post dose (60 mins) * any treatment-related AE that led to participant not being able to complete the test dose * \>20% reduction in FEV1 pre dose to post dose at 60min if additionally reporting troublesome cough, chest pain or tightness, bronchospasm or dyspnoea that is deemed unacceptable by the patient

Group	Value	95% CI
SAD-1ml	8
SAD - 2ml	8
SAD - 3ml	8
SAD - 4ml	8
SAD - 5ml	8
SAD - 6ml	6
MTD 6ml +SABA MTD 6ml +SABA MTD 6ml +SABA	8

Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2) Secondary · Screening Visit

Defined as percentage of participants able to tolerate the test dose, i.e. able to complete the test dose without any of the following: * Troublesome cough, chest pain or tightness, bronchospasm or dyspnoea that is deemed unacceptable by the patient * methaemoglobin \>5% during or \>3% post dose (60 mins) * any treatment-related AE that led to participant not being able to complete the test dose, and/or be suitable to be enrolled into the dormant phase in the Investigator's opinion * for the first 50 patients who will undergo pre spirometry, \>20% reduction in FEV1 from pre test dose to post

Group	Value	95% CI
SAD - 1ml	8
SAD - 2ml	8
SAD - 3ml	8
SAD - 4ml	8
SAD - 5ml	8
SAD - 6ml	4
MTD 6ml +SABA MTD 6ml +SABA MTD 6ml +SABA	7
RTD - 4ml	12

Safety of RESP301 in Terms of Treatment Emergent Adverse Events Secondary · 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)

Defined as total counts and cumulative incidence of Treatment Emergent Adverse Events (TEAEs)

Group	Value	95% CI
SAD - 1ml	4
SAD - 2ml	7
SAD - 3ml	3
SAD - 4ml	8
SAD - 5ml	10
SAD - 6ml	13
MTD 6ml +SABA	13
RTD 4ml	16

Safety of RESP301 in Terms of Serious Adverse Events Secondary · 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)

Defined as total counts and cumulative incidence of Serious Adverse Events (SAEs)

Group	Value	95% CI
SAD - 1ml	0
SAD - 2ml	0
SAD - 3ml	0
SAD - 4ml	0
SAD - 5ml	0
SAD - 6ml	0
MTD 6ml +SABA	0
RTD - 4ml	6

Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions Secondary · 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)

Defined as total counts and cumulative incidence of Suspected Unexpected Serious Adverse Reactions (SUSARs)

Group	Value	95% CI
SAD - 1ml	0
SAD - 2ml	0
SAD - 3ml	0
SAD - 4ml	0
SAD - 5ml	0
SAD - 6ml	0
MTD 6ml + SABA	0
RTD 4ml	1

Safety of RESP301 in Terms of Treatment-related AEs Secondary · 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)

Defined as total counts and cumulative incidence of treatment-related AEs

Group	Value	95% CI
SAD - 1ml	4
SAD - 2ml	4
SAD - 3ml	2
SAD - 4ml	7
SAD - 5ml	8
SAD - 6ml	12
MTD 6ml +SABA	12
RTD 4ml	16

Adverse events — posted to ClinicalTrials.gov

Time frame: Part 0: Screening/baseline visit Day 0. 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). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 0

Serious: 0/4 (0%)

Deaths: 0/4

Part 1A - 1ml

Serious: 0/8 (0%)

Deaths: 0/8

Part 1A - 2ml

Serious: 0/8 (0%)

Deaths: 0/8

Part 1A - 3ml

Serious: 0/8 (0%)

Deaths: 0/8

Part 1A - 4ml

Serious: 0/8 (0%)

Deaths: 0/8

Part 1A - 5ml

Serious: 0/8 (0%)

Deaths: 0/8

Part 1A - 6ml

Serious: 0/6 (0%)

Deaths: 0/6

Part 1B - 6ml +SABA

Serious: 1/8 (13%)

Deaths: 0/8

Part 2 - RTD 4ml RTD 4ml RTD 4ml

Serious: 4/16 (25%)

Deaths: 0/16

Serious adverse events (6 terms)

Reaction	System	Part 0	Part 1A - 1ml	Part 1A - 2ml	Part 1A - 3ml	Part 1A - 4ml	Part 1A - 5ml	Part 1A - 6ml	Part 1B - 6ml +SABA	Part 2 - RTD 4ml RTD 4ml R…
COVID-19	Infections and infestations	—	—	—	—	—	—	—	—	—
Decompensated heart failure	Cardiac disorders	—	—	—	—	—	—	—	—	—
End stage COPD	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Lobar collapse	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Compressed Fracture	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Severe Bronchospasm	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—

Other adverse events (2 terms — click to expand)

Reaction	System	Part 0	Part 1A - 1ml	Part 1A - 2ml	Part 1A - 3ml	Part 1A - 4ml	Part 1A - 5ml	Part 1A - 6ml	Part 1B - 6ml +SABA	Part 2 - RTD 4ml RTD 4ml R…
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—

Most-reported serious reactions: COVID-19, Decompensated heart failure, End stage COPD, Lobar collapse, Compressed Fracture, Severe Bronchospasm.

Data from ClinicalTrials.gov NCT04858451 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. A roadmap to pulmonary delivery strategies for the treatment of infectious lung diseases.
   He S, Gui J, Xiong K, Chen M, et al · · 2022 · cited 91× · PMID 35241085 · DOI 10.1186/s12951-022-01307-x
2. Potential Prophylactic Treatments for COVID-19.
   Ben-Zuk N, Dechtman ID, Henn I, Weiss L, et al · · 2021 · cited 9× · PMID 34372498 · DOI 10.3390/v13071292
3. Utility of NO and H₂S donating platforms in managing COVID-19: Rationale and promise.
   Oza PP, Kashfi K. · · 2022 · cited 6× · PMID 36029975 · DOI 10.1016/j.niox.2022.08.003