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

Phase 2TerminatedNCT04858451

Thirty Respiratory Limited88 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Eligibility

Sex: ALLMin age: 35 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1

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

Time frame: Screening Visit

Feasibility of Self-administering RESP301 Treatment in Terms of Commencing Treatment

Defined as percentage of patients who, having experienced and correctly reported an exacerbation, commence self-administration of the treatment on the day the treatment is delivered

Time frame: 1 day

Feasibility of Self-administering RESP301 Treatment in Terms of Treatment Compliance

For those participants commencing self-administration of RESP301, the percentage of total doses taken

Time frame: 7 days

Secondary Outcomes

Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2)

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 test dose with symptoms (patients with \>20% reduction in FEV1 without symptoms would be offered the option to continue in the study)

Time frame: Screening Visit

Safety of RESP301 in Terms of Treatment Emergent Adverse Events

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

Time frame: 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)

Safety of RESP301 in Terms of Serious Adverse Events

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

Time frame: 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)

Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions

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

Time frame: 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)

Safety of RESP301 in Terms of Treatment-related AEs

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

Time frame: 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)

Efficacy of RESP301 in Terms of Percentage of Patients Recovered by Day 7

Defined as percentage of participants recovered by Day 7 post starting treatment, where recovery is defined as patient feels all their symptoms are back to their usual baseline (all symptom Visual Analogue Scores are 0 on a scale from 0 to 10, where 0 is "same as usual" and 10 is "much more than usual")

Time frame: 7 days

Efficacy of RESP301 in Terms of Percentage of Patients Recovered by Day 14

Defined as percentage of participants recovered by Day 14 post starting treatment, where recovery is defined as patient feels all their symptoms are back to their usual baseline (all symptom Visual Analogue Scores are 0 on a scale from 0 to 10, where 0 is "same as usual" and 10 is "much more than usual")

Time frame: 7 days

Efficacy of RESP301 in Terms of Time to Recovery

Defined as days to recovery, where recovery is defined as patient feels all their symptoms are back to their usual baseline (all symptom Visual Analogue Scores are 0 on a scale from 0 to 10, where 0 is "same as usual" and 10 is "much more than Defined as percentage of participants recovered by Day 14 post starting treatment, where recovery is defined as patient feels all their symptoms are back to their usual baseline (all symptom Visual Analogue Scores are 0 on a scale from 0 to 10, where 0 is "same as usual" and 10 is "much more than usual")

Time frame: 21 days

Efficacy of RESP301 in Terms of Preventing Exacerbation-related Hospitalisation and/or Death

Number of patients treated with RESP301 that experience exacerbation-related hospitalisation and/or death

Time frame: 7 days

Efficacy of RESP301 in Terms of Patient-reported Symptoms

Change in Clinical COPD Questionnaire (CCQ) score from Day 1 to Day 7, where the minimum score is 0 (very good health status) and maximum score is 6 (extremely poor health status)

Time frame: 7 days

Feasibility of Self-administering RESP301 Treatment in Terms of Receiving Treatment

Defined as percentage of patients who, having experienced and correctly reported an exacerbation, receive the treatment within 48 hours of reporting their exacerbation

Time frame: 2 days

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

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes