COVID-19 (Coronavirus Disease 2019)Phase 2COVASENCT04359654
Nebulised Dornase Alfa for Treatment of COVID-19 (Coronavirus Disease 2019)
A Phase 2 study testing Dornase Alfa Inhalation Solution [Pulmozyme] in people with COVID-19 (Coronavirus Disease 2019) and Hypoxia, run by University College, London at 1 site in United Kingdom.
Trial summary
An open-label, randomised, Best-Available-Care (BAC) and historic-controlled trial of nebulised dornase alfa [2.5 mg BID (bis in die)] for 7 days in participants with COVID-19 who are admitted to hospital and are at risk of ventilatory failure (the COVASE study). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- COVID-19 (Coronavirus Disease 2019), Hypoxia
- What is being tested?
- Dornase Alfa Inhalation Solution [Pulmozyme]
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 16 Jun 2020to 5 Nov 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female participants, aged ≥ 18 years.
- Participants who are hospitalised for suspected Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test or radiological confirmation.
- Participants with stable oxygen saturation (>=94%) on supplementary oxygen
- CRP >= 30 mg/L.
- Participants will have given their written informed consent to participate in the study and are able to comply with instructions and nebuliser.
Who cannot join
- Females who are pregnant, planning pregnancy or breastfeeding.
- Concurrent and/or recent involvement in other research or use of another experimental investigational medicinal product that is likely to interfere with the study medication within the last 3 months before study enrolment.
- Serious condition meeting one of the following:
- respiratory distress with respiratory rate >=40 breaths/min II. oxygen saturation <=93% on high-flow oxygen
- Require mechanical invasive or non-invasive ventilation at screening
- Concurrent severe respiratory disease such as asthma, COPD (chronic obstructive pulmonary disease) and/or ILD (interstitial lung disease).
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- Any major disorder that in the opinion of the Investigator would interfere with the evaluation of the results or constitute a health risk for the study participant.
- Terminal disease and life expectancy <12 months without COVID-19.
- Known allergies to the dornase alfa and excipients.
- Participants who are unable to inhale or exhale orally throughout the entire nebulisation period.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University College London Hospital
London, NW1 2BU
About this study
Official title: A Single-site, Randomised, Controlled, Parallel Design, Open-label Investigation of an Approved Nebulised Recombinant Human DNase Enzyme (Dornase Alfa) to Reduce Hyperinflammation in Hospitalised Participants With COVID-19
An open-label, randomised, Best-Available-Care (BAC) and historic-controlled trial of nebulised dornase alfa [2.5 mg BID (bis in die)] for 7 days in participants with COVID-19 who are admitted to hospital and are at risk of ventilatory failure (the COVASE study). Controls will include a randomised arm to receive BAC, historic data from University College London Hospitals NHS Foundation Trust (UCLH) patients with COVID-19 and biobanked samples will be used to demonstrate an effect of dornase alfa. C-reactive protein (CRP) will be measured to assess the effect of dornase alfa on inflammation. Clinical endpoints and biomarkers (e.g. d-dimer) will be used to assess the clinical response. Exploratory endpoints will explore the effects of dornase alfa on features of neutrophil extracellular traps (NETs).
Read the detailed description
Dornase alfa is a recombinant human DNase enzyme indicated in conjunction with standard therapies for the management of cystic fibrosis (CF) to improve pulmonary function. Dornase alfa degrades extracellular DNA, and so promotes the clearance of NETs and lead to a significant improvement in lung function for treated CF patients by facilitating mucus clearance in the lung. Dornase alfa is approved worldwide as a nebulised formulation, with an excellent safety profile and is well tolerated. The most common side effect is a hoarse voice. Moreover, dornase alfa could be administered in addition to effective antiviral therapy and should not interfere with antiviral drugs that could be used for COVID-19.
By facilitating the clearance of NETs, dornase alfa not only facilitates sputum clearance in CF patients, but has additional anti-inflammatory activity. Dornase alfa has been shown to reduce NETs in the bronchoalveolar lavage (BAL) and sputum of participants with CF (Konstan et al 2012). In the Bronchoalveolar Lavage for the Evaluation of Anti-inflammatory Treatment (BEAT) study, the percentage of neutrophils in bronchoalveolar lavage fluid significantly increased in untreated CF patients (P<0.02) while remaining constant in the dornase alfa-treated group. Levels of elastase and IL-8 also significantly increased from baseline in the untreated group (P<0.007 and P<0.02 for elastase and IL-8, respectively), but remained stable in patients receiving dornase alfa (Konstan and Ratjen, J. Cyst. Fibros. 2012).
There is scientific evidence to support the potential benefits of dornase alfa in COVID-19 infection. Viral sepsis driven by a hyperinflammation is thought to be a major cause of mortality in COVID-19 infection. Interleukin-1β (IL-1β), IL-6 and TNFα (tumour necrosis factor alpha) are key cytokines in microbial sepsis. Positive outcomes with Roche's Actemra (tocilizumab), an antibody that blocks the pro-inflammatory cytokine interleukin-6 (IL-6), in COVID-19 treatment has led to several anti-inflammatory trials.
Our hypothesis is that nebulised dornase alfa will break down the DNA backbone of NETs in the COVID-19 lung which will promote the degradation of pro-inflammatory extracellular histones and prevent the amplification of the inflammatory response and the resultant lung damage.
Positive data will enable rapid testing into a large clinical trial in the UK (United Kingdom) and prevent ICU (intensive care unit) capacity issues faced today. Dornase alfa is a cost-effective drug and is currently available for prescription.
We propose to test this hypothesis with this COVASE Phase 2a trial. We propose that all people with COVID-19 who are admitted to hospital for supplementary oxygen, who showed evidence of systemic inflammation but did not immediately require intubation and ventilation, would be eligible for nebulised Dornase alfa, a safe and cost-effective treatment, twice daily for 7 days.
- Conditions
- COVID-19 (Coronavirus Disease 2019), Hypoxia
- Being tested
- Dornase Alfa Inhalation Solution [Pulmozyme]
- Keywords
- COVID, COVID19, Pneumonia, Coronavirus, Hypoxia, C-Reactive Protein
- Medical subject headings
- COVID-19, Hypoxia, Pneumonia, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dornase Alfa Inhalation Solution [Pulmozyme]Drug
Nebulised Dornase alfa 2.5mg bd for 7 days
| Study group | Role | What they receive |
|---|---|---|
| Dornase alfa treatment | Experimental | Best available care and nebulised dornase alfa [2.5 mg BID] for 7 days in participants with COVID-19 who are admitted to hospital and are at risk of ventilatory failure Receives: Drug: Dornase Alfa Inhalation Solution [Pulmozyme] |
| Best available care | No intervention | Best available standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measuring the Change in Inflammation
Analysing stabilisation of C-reactive protein.
Measured: 7 days
Secondary outcomes (4)
Survival at 35 Days
Survival at 35 days (28 days post last treatment day) Participants were followed up until discharge or death or a maximum of 28 days post last treatment day.
Measured: 35 days
Discharge Before 35 Days
Number of participants discharged before 35 days
Measured: Before 35 days
D-dimer (ug/L)
Change in D-dimer (ug/L) The reported LS means are antilogs of the LS means estimated on the log scale.
Measured: 7 days
Lymphocyte Count (×109/L)
measure of Lymphocyte count (×109/L)
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2020
- Study start16 Jun 2020
- Primary completion12 Aug 2021
- Study completion5 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19 (Coronavirus Disease 2019)Studies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- An open-label, randomised, Best-Available-Care (BAC) and historic-controlled trial of nebulised dornase alfa \[2.5 mg BID\] for 7 days in participants with COVID-19 who are admitted to hospital and are at risk of ventilatory failure
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joanna Porter, MD PhD, Principal investigator, University College, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04359654
- Sponsor's protocol ID
- 132333
- Acronym
- COVASE
- Status last verified
- Jan 2025
- First submitted
- 21 Apr 2020
- Last updated
- 13 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Anonymised results will be published in a scientific journal (TBC) and posted on the Breathing Matters website www.breathingatters@ucl.ac.uk
Publications
Porter JC, Inshaw J, Solis VJ, Denneny E, Evans R, Temkin MI, De Vasconcelos N, Aramburu IV, Hoving D, Basire D, Crissell T, Guinto J, Webb A, Esmail H, Johnston V, Last A, Rampling T, Lippert L, Helbig ET, Kurth F, Williams B, Flynn A, Lukey PT, Birault V, Papayannopoulos V. Anti-inflammatory therapy with nebulized dornase alfa for severe COVID-19 pneumonia: a randomized unblinded trial. Elife. 2024 Jul 16;12:RP87030. doi: 10.7554/eLife.87030.
PubMed 39009040
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-site, Randomised, Controlled, Parallel Design, Open-label Investigation of an Approved Nebulised Recombinant Human DNase Enzyme (Dornase Alfa) to Reduce Hyperinflammation in Hospitalised Participants With COVID-19
- ClinicalTrials.gov ID
- NCT04359654
- Acronym / sponsor ID
- COVASE / 132333
- Conditions
- COVID-19 (Coronavirus Disease 2019), Hypoxia
- Keywords
- COVID, COVID19, Pneumonia, Coronavirus, Hypoxia, C-Reactive Protein
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- 16 Jun 2020 (actual)
- Primary completion
- 12 Aug 2021 (actual)
- Study completion
- 5 Nov 2021 (actual)
- First posted
- 24 Apr 2020 (actual)
- Results
- Posted 13 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An open-label, randomised, Best-Available-Care (BAC) and historic-controlled trial of nebulised dornase alfa [2.5 mg BID (bis in die)] for 7 days in participants with COVID-19 who are admitted to hospital and are at risk of ventilatory failure (the COVASE study). Controls will include a randomised arm to receive BAC, historic data from University College London Hospitals NHS Foundation Trust (UCLH) patients with COVID-19 and biobanked samples will be used to demonstrate an effect of dornase alfa. C-reactive protein (CRP) will be measured to assess the effect of dornase alfa on inflammation. Clinical endpoints and biomarkers (e.g. d-dimer) will be used to assess the clinical response. Exploratory endpoints will explore the effects of dornase alfa on features of neutrophil extracellular traps (NETs).
Detailed description
Dornase alfa is a recombinant human DNase enzyme indicated in conjunction with standard therapies for the management of cystic fibrosis (CF) to improve pulmonary function. Dornase alfa degrades extracellular DNA, and so promotes the clearance of NETs and lead to a significant improvement in lung function for treated CF patients by facilitating mucus clearance in the lung. Dornase alfa is approved worldwide as a nebulised formulation, with an excellent safety profile and is well tolerated. The most common side effect is a hoarse voice. Moreover, dornase alfa could be administered in addition to effective antiviral therapy and should not interfere with antiviral drugs that could be used for COVID-19.
By facilitating the clearance of NETs, dornase alfa not only facilitates sputum clearance in CF patients, but has additional anti-inflammatory activity. Dornase alfa has been shown to reduce NETs in the bronchoalveolar lavage (BAL) and sputum of participants with CF (Konstan et al 2012). In the Bronchoalveolar Lavage for the Evaluation of Anti-inflammatory Treatment (BEAT) study, the percentage of neutrophils in bronchoalveolar lavage fluid significantly increased in untreated CF patients (P<0.02) while remaining constant in the dornase alfa-treated group. Levels of elastase and IL-8 also significantly increased from baseline in the untreated group (P<0.007 and P<0.02 for elastase and IL-8, respectively), but remained stable in patients receiving dornase alfa (Konstan and Ratjen, J. Cyst. Fibros. 2012).
There is scientific evidence to support the potential benefits of dornase alfa in COVID-19 infection. Viral sepsis driven by a hyperinflammation is thought to be a major cause of mortality in COVID-19 infection. Interleukin-1β (IL-1β), IL-6 and TNFα (tumour necrosis factor alpha) are key cytokines in microbial sepsis. Positive outcomes with Roche's Actemra (tocilizumab), an antibody that blocks the pro-inflammatory cytokine interleukin-6 (IL-6), in COVID-19 treatment has led to several anti-inflammatory trials.
Our hypothesis is that nebulised dornase alfa will break down the DNA backbone of NETs in the COVID-19 lung which will promote the degradation of pro-inflammatory extracellular histones and prevent the amplification of the inflammatory response and the resultant lung damage.
Positive data will enable rapid testing into a large clinical trial in the UK (United Kingdom) and prevent ICU (intensive care unit) capacity issues faced today. Dornase alfa is a cost-effective drug and is currently available for prescription.
We propose to test this hypothesis with this COVASE Phase 2a trial. We propose that all people with COVID-19 who are admitted to hospital for supplementary oxygen, who showed evidence of systemic inflammation but did not immediately require intubation and ventilation, would be eligible for nebulised Dornase alfa, a safe and cost-effective treatment, twice daily for 7 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- An open-label, randomised, Best-Available-Care (BAC) and historic-controlled trial of nebulised dornase alfa [2.5 mg BID] for 7 days in participants with COVID-19 who are admitted to hospital and are at risk of ventilatory failure
| Arm | Type | Receives |
|---|---|---|
| Dornase alfa treatment | Experimental | Drug: Dornase Alfa Inhalation Solution [Pulmozyme]Best available care and nebulised dornase alfa [2.5 mg BID] for 7 days in participants with COVID-19 who are admitted to hospital and are at risk of ventilatory failure |
| Best available care | No intervention | –Best available standard of care |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male and female participants, aged ≥ 18 years.
- Participants who are hospitalised for suspected Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test or radiological confirmation.
- Participants with stable oxygen saturation (>=94%) on supplementary oxygen
- CRP >= 30 mg/L.
- Participants will have given their written informed consent to participate in the study and are able to comply with instructions and nebuliser.
Key exclusion criteria (10 listed)
- Females who are pregnant, planning pregnancy or breastfeeding.
- Concurrent and/or recent involvement in other research or use of another experimental investigational medicinal product that is likely to interfere with the study medication within the last 3 months before study enrolment.
- Serious condition meeting one of the following:
- Require mechanical invasive or non-invasive ventilation at screening
- Concurrent severe respiratory disease such as asthma, COPD (chronic obstructive pulmonary disease) and/or ILD (interstitial lung disease).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dornase Alfa Inhalation Solution [Pulmozyme]Nebulised Dornase alfa 2.5mg bd for 7 days | Drug | Dornase alfa treatment |
Primary outcome
Measuring the Change in Inflammation
Time frame: 7 days
Analysing stabilisation of C-reactive protein.
4 secondary outcomes
Survival at 35 Days
Time frame: 35 days
Discharge Before 35 Days
Time frame: Before 35 days
D-dimer (ug/L)
Time frame: 7 days
Lymphocyte Count (×109/L)
Time frame: 7 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39009040Porter JC, Inshaw J, Solis VJ, Denneny E, Evans R, Temkin MI, De Vasconcelos N, Aramburu IV, Hoving D, Basire D, Crissell T, Guinto J, Webb A, Esmail H, Johnston V, Last A, Rampling T, Lippert L, Helbig ET, Kurth F, Williams B, Flynn A, Lukey PT, Birault V, Papayannopoulos V. Anti-inflammatory therapy with nebulized dornase alfa for severe COVID-19 pneumonia: a randomized unblinded trial. Elife. 2024 Jul 16;12:RP87030. doi: 10.7554/eLife.87030.
- Individual participant dataSharing planned: No. Anonymised results will be published in a scientific journal (TBC) and posted on the Breathing Matters website www.breathingatters@ucl.ac.uk
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joanna Porter, MD PhD principal investigator
University College, London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dornase Alfa Inhalation Solution [Pulmozyme] in people with COVID-19 (Coronavirus Disease 2019) and Hypoxia, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measuring the Change in Inflammation (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04359654, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2025.