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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04858451
Recruitment Status : Recruiting
First Posted : April 26, 2021
Last Update Posted : December 27, 2021
Sponsor:
Information provided by (Responsible Party):
Thirty Respiratory Limited

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.


Condition or disease Intervention/treatment Phase
COPD Bronchiectasis Drug: RESP301 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
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.

Masking: None (Open Label)
Primary Purpose: Other
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)
Actual Study Start Date : April 30, 2021
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Viral Infections

Arm Intervention/treatment
Experimental: 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.

Drug: 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.





Primary Outcome Measures :
  1. Proportion of patients tolerating RESP301 at each dose level in Part 1 [ Time Frame: 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

  2. Feasibility of self-administering RESP301 treatment in terms of commencing treatment [ Time Frame: 1 day ]
    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

  3. Feasibility of self-administering RESP301 treatment in terms of treatment compliance [ Time Frame: 7 days ]
    For those participants commencing treatment, the percentage of total doses taken


Secondary Outcome Measures :
  1. Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2) [ Time Frame: 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 test dose with symptoms (patients with >20% reduction in FEV1 without symptoms would be offered the option to continue in the study)

  2. Safety of RESP301 in terms of Adverse Events [ Time Frame: Screening Visit; Treatment phase + follow-up period (7 + 28 days) ]
    Defined as total counts and cumulative incidence of Adverse Events (AEs)

  3. Safety of RESP301 in terms of Serious Adverse Events [ Time Frame: Screening Visit; Treatment phase + follow-up period (7 + 28 days) ]
    Defined as total counts and cumulative incidence of Serious Adverse Events (SAEs)

  4. Safety of RESP301 in terms of Suspected Unexpected Serious Adverse Reactions [ Time Frame: Screening Visit; Treatment phase + follow-up period (7 + 28 days) ]
    Defined as total counts and cumulative incidence of Suspected Unexpected Serious Adverse Reactions (SUSARs)

  5. Safety of RESP301 in terms of Severe AEs [ Time Frame: Screening Visit; Treatment phase + follow-up period (7 + 28 days) ]
    Defined as total counts and cumulative incidence of Severe AEs

  6. Safety of RESP301 in terms of treatment-related AEs and SAEs [ Time Frame: Screening Visit; Treatment phase + follow-up period (7 + 28 days) ]
    Defined as total counts and cumulative incidence of treatment-related AEs and SAEs

  7. Efficacy of RESP301 in terms of percentage of patients recovered by Day 7 [ Time Frame: 7 days ]
    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")

  8. Efficacy of RESP301 in terms of percentage of patients recovered by Day 14 [ Time Frame: 7 days ]
    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")

  9. Efficacy of RESP301 in terms of time to recovery [ Time Frame: 21 days ]
    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")

  10. Efficacy of RESP301 in terms of preventing exacerbation-related hospitalisation and/or death [ Time Frame: 7 days ]
    Number of patients with exacerbation-related hospitalisation and/or death

  11. Efficacy of RESP301 in terms of patient-reported symptoms [ Time Frame: 7 days ]
    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)

  12. Feasibility of self-administering RESP301 treatment in terms of receiving treatment [ Time Frame: 2 days ]
    Defined as percentage of patients who, having experienced and correctly reported an exacerbation, receive the treatment within 48 hours of reporting their exacerbation



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   35 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04858451


Contacts
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Contact: Alison Bracchi +44(0)1235431200 alison.bracchi@30.technology

Locations
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United Kingdom
Medicines Evaluation Unit Recruiting
Manchester, United Kingdom
Contact: Dave Singh, Prof.         
The Newcastle upon Tyne Hospitals NHS Foundation Trust Not yet recruiting
Newcastle Upon Tyne, United Kingdom
Contact: Anthony De Soyza, Prof.         
Sponsors and Collaborators
Thirty Respiratory Limited
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Responsible Party: Thirty Respiratory Limited
ClinicalTrials.gov Identifier: NCT04858451    
Other Study ID Numbers: RESP301-005
First Posted: April 26, 2021    Key Record Dates
Last Update Posted: December 27, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Virus Diseases
Bronchiectasis
Infections
Bronchial Diseases
Respiratory Tract Diseases