COVID-19Phase 3NCT04459325
Tigerase® Efficacy and Safety as Part of Complex Therapy in Patients With COVID-19
A Phase 3 study testing Tigerase® and best available care and Best available care in people with COVID-19 and Coronavirus Disease 2019, run by AO GENERIUM at 6 sites in Russia.
Trial summary
It is a multicenter, open-label, randomized, parallel-group study of the efficacy and safety of Tigerase® (GENERIUM JSC, Russia) with standard therapy versus standard therapy in patients with COVID-19. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, Coronavirus Disease 2019
- What is being tested?
- Tigerase® and best available care and Best available care
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 6 sitesRussia
- Study dates
- 1 Jun 2020to 20 Jul 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent for participation in the study
- Men and women aged ≥18 years
- Laboratory-confirmed diagnosis of coronavirus infection caused by COVID19, moderate severity *
- Criteria for moderate flow (just one point) Mandatory Criterion
- Pneumonia Additional criteria (used to characterize the disease and are not required to determine the severity)
- Fever above 38 ° C
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- respiratory rate more than 22 / min
- Shortness of breath during physical exertion
- SpO2 <95%
- С-reactive protein (CRP) of serum more than 10 mg / l
- Patients with pneumonia with a stable level of hemoglobin saturation by oxygen (> 93%) on oxygen support and / or receiving respiratory support of non-invasive mechanical ventilation
Who cannot join
- Individual intolerance or hypersensitivity to the active or any of the excipients of the drug Tigerase®
- The need for invasive mechanical ventilation at the time of inclusion of the patient
- Patients severe condition (one of the following characteristics):
- Respiratory distress syndrome with respiratory rate ≥30 per minute
- Saturation of hemoglobin with oxygen ≤93% with oxygen support
- Patient participate in any clinical trials and / or taking the experimental drug within 30 days before inclusion this trial
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- Severe competitive respiratory system diseases (bronchial asthma, chronic obstructive pulmonary disease - COPD, cystic fibrosis, interstitial lung disease)
- Positive results of laboratory testing for HIV and hepatitis B and C
- Life expectancy less than 12 months without COVID-19
- Other diseases and conditions, significant laboratory or instrumental deviation, which, according to investigator opinion, may impact the results of the study, limit the patient's participation in the trial or create an unreasonable risk for the patient
- Patient's unwillingness or disability to comply with the recommendations prescribed by protocol, as well as any concomitant medical or serious mental conditions that render the patient unsuitable for participation in the study, limit the legitimacy of obtaining informed consent or may affect the patient's ability to participate in the study (including disability to use a nebulizer)
- Positive pregnancy test in women
- The period of breastfeeding in women
- Refusal of male patients and female patients with preserved reproductive function to use adequate methods of contraception throughout the study and for at least 30 days after the end of therapy with the studied drug
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Russia6 sites
City Clinical Hospital #15
Moscow, 111539
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Moscow, 119991
City Clinical Hospital #51
Moscow, 121309
City Clinical Hospital #52
Moscow, 123182
N.V. Sklifosovsky Scientific Research Institute of First Aid
Moscow, 129090
Siberian State Medical University (SibMed)
Moscow, 634050
About this study
Official title: A Prospective Open-label Study of the Tigerase® Efficacy and Safety as Part of Complex Therapy in Patients With COVID-19
It is a multicenter, open-label, randomized, parallel-group study of the efficacy and safety of Tigerase® (GENERIUM JSC, Russia) with standard therapy versus standard therapy in patients with COVID-19.
Read the detailed description
COVID-19 (Coronavirus disease-19) is an acute respiratory infectious disease caused by SARS-CoV-2 coronavirus. The spread of the disease quickly developed to the global pandemic in March-April 2020, and was characterized by acute respiratory distress syndrome (ARDS) in 10-15% of cases, which leads to a high frequency of hospitalization in the intensive care unit and high mortality. The search for effective treatment and reducing the severity of COVID-19 is a priority in the development of medical science.
One of the key processes of the innate immune system are neutrophil extracellular traps (NET), formed by neutrophils when they eject their DNA from the cytoplasm. NET is most often described as a mechanism for capturing bacteria in order to limit their spread. In addition, NET also plays a role in antiviral immunity. In particular, viral infections lung damage is at least partially due to NET.
This suggests that drug disruption of NET in COVID-19 is promising. DNase preparations, and in particular Tigerase®, are safe and effective for the treatment of cystic fibrosis and can serve as a NET destruction agent in patient with COVID-19.
- Conditions
- COVID-19, Coronavirus Disease 2019
- Being tested
- Tigerase® and best available care, Best available care
- Keywords
- COVID-19, Coronavirus Infections, Coronaviridae Infections, Dornase alfa, Virus Diseases, Acute lung injury, Acute respiratory distress syndrome, Respiratory Insufficiency, Respiratory Tract Diseases
- Medical subject headings
- COVID-19, Coronavirus Infections, Coronaviridae Infections, Virus Diseases, Acute Lung Injury, Respiratory Distress Syndrome, Respiratory Insufficiency, Respiratory Tract Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tigerase® and best available careBiological
Also called Dornase Alfa Inhalation Solution and best available care
Nebulised dornase alfa [2.5 mg BID] for 7 days
Best available careOther
Also called Standard of care
Patients will receive the usual care in accordance with good practice.
| Study group | Role | What they receive |
|---|---|---|
| Study drug and best available care | Experimental | Best available care and Tigerase®/nebulised dornase alfa [2.5 mg BID] for 7 days Receives: Biological: Tigerase® and best available care |
| Control group (best available care) | Other | Patients will receive the usual care in accordance with good practice. Receives: Other: Best available care |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of patients with mechanical ventilation
Measured: Day 8
Category change on WHO Ordinal Scale for Clinical Improvement
Measured: Day 8
Secondary outcomes (12)
The proportion of patients with mechanical ventilation
Measured: Day 28
Category change on WHO Ordinal Scale for Clinical Improvement
Measured: Day 28
Proportion of patients surviving 28 days after inclusion in the study
Measured: Day 28
Number of days of oxygen therapy during the treatment period
Measured: Day 8
Change in C-reactive protein level
Measured: Days 3, 5, 8
Change in oxygenation index
PaO2 / FiO2, FiO2 = fraction of oxygen in inhaled air,% PaO2 = partial pressure of oxygen in arterial blood, mm Hg
Measured: Days 3, 5, 8
Change in SpO2/FiO2 index
SpO2 / FiO2, FiO2 = fraction of oxygen in inhaled air,% SpO2 = hemoglobin oxygen saturation, %
Measured: Days 1, 2, 3, 4, 5, 6, 7, 8
Change in ferritin level
Measured: Days 3, 5, 8
Change in D-dimer level
Measured: Days 3, 5, 8
Change in neutrophil-leucocyte ratio
Measured: Days 3, 5, 8
Change in leucocyte-C-reactive protein ratio
Measured: Days 3, 5, 8
Change in the level of relative (%) number of lymphocytes of the general blood test
Measured: Days 3, 5, 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2020
- Study start1 Jun 2020
- Primary completion20 Jul 2020
- Study completion20 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- AO GENERIUM
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Oksana A. Markova, MD, Study chair, AO GENERIUM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04459325
- Sponsor's protocol ID
- DRN-ALI-III
- Other IDs
- #216 eff date 27.05.2020
- Status last verified
- Jul 2020
- First submitted
- 3 Jul 2020
- Last updated
- 14 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Open-label Study of the Tigerase® Efficacy and Safety as Part of Complex Therapy in Patients With COVID-19
- ClinicalTrials.gov ID
- NCT04459325
- Acronym / sponsor ID
- DRN-ALI-III
- Conditions
- COVID-19, Coronavirus Disease 2019
- Keywords
- COVID-19, Coronavirus Infections, Coronaviridae Infections, Dornase alfa, Virus Diseases, Acute lung injury, Acute respiratory distress syndrome, Respiratory Insufficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- AO GENERIUMIndustry (pharma, biotech, devices)
- Study start
- 1 Jun 2020 (actual)
- Primary completion
- 20 Jul 2020 (actual)
- Study completion
- 20 Jul 2020 (actual)
- First posted
- 7 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
It is a multicenter, open-label, randomized, parallel-group study of the efficacy and safety of Tigerase® (GENERIUM JSC, Russia) with standard therapy versus standard therapy in patients with COVID-19.
Detailed description
COVID-19 (Coronavirus disease-19) is an acute respiratory infectious disease caused by SARS-CoV-2 coronavirus. The spread of the disease quickly developed to the global pandemic in March-April 2020, and was characterized by acute respiratory distress syndrome (ARDS) in 10-15% of cases, which leads to a high frequency of hospitalization in the intensive care unit and high mortality. The search for effective treatment and reducing the severity of COVID-19 is a priority in the development of medical science.
One of the key processes of the innate immune system are neutrophil extracellular traps (NET), formed by neutrophils when they eject their DNA from the cytoplasm. NET is most often described as a mechanism for capturing bacteria in order to limit their spread. In addition, NET also plays a role in antiviral immunity. In particular, viral infections lung damage is at least partially due to NET.
This suggests that drug disruption of NET in COVID-19 is promising. DNase preparations, and in particular Tigerase®, are safe and effective for the treatment of cystic fibrosis and can serve as a NET destruction agent in patient with COVID-19.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study drug and best available care | Experimental | Biological: Tigerase® and best available careBest available care and Tigerase®/nebulised dornase alfa [2.5 mg BID] for 7 days |
| Control group (best available care) | Other | Other: Best available carePatients will receive the usual care in accordance with good practice. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Written informed consent for participation in the study
- Men and women aged ≥18 years
- Laboratory-confirmed diagnosis of coronavirus infection caused by COVID19, moderate severity *
- Criteria for moderate flow (just one point) Mandatory Criterion
- Patients with pneumonia with a stable level of hemoglobin saturation by oxygen (> 93%) on oxygen support and / or receiving respiratory support of non-invasive mechanical ventilation
Key exclusion criteria (14 listed)
- Individual intolerance or hypersensitivity to the active or any of the excipients of the drug Tigerase®
- The need for invasive mechanical ventilation at the time of inclusion of the patient
- Patients severe condition (one of the following characteristics):
- Patient participate in any clinical trials and / or taking the experimental drug within 30 days before inclusion this trial
- Severe competitive respiratory system diseases (bronchial asthma, chronic obstructive pulmonary disease - COPD, cystic fibrosis, 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 |
|---|---|---|
| Tigerase® and best available careAlso: Dornase Alfa Inhalation Solution and best available careNebulised dornase alfa [2.5 mg BID] for 7 days | Biological | Study drug and best available care |
| Best available careAlso: Standard of carePatients will receive the usual care in accordance with good practice. | Other | Control group (best available care) |
Primary outcome
The proportion of patients with mechanical ventilation
Time frame: Day 8
Category change on WHO Ordinal Scale for Clinical Improvement
Time frame: Day 8
12 secondary outcomes
The proportion of patients with mechanical ventilation
Time frame: Day 28
Category change on WHO Ordinal Scale for Clinical Improvement
Time frame: Day 28
Proportion of patients surviving 28 days after inclusion in the study
Time frame: Day 28
Number of days of oxygen therapy during the treatment period
Time frame: Day 8
Change in C-reactive protein level
Time frame: Days 3, 5, 8
Change in oxygenation index
Time frame: Days 3, 5, 8
Change in SpO2/FiO2 index
Time frame: Days 1, 2, 3, 4, 5, 6, 7, 8
Change in ferritin level
Time frame: Days 3, 5, 8
Change in D-dimer level
Time frame: Days 3, 5, 8
Change in neutrophil-leucocyte ratio
Time frame: Days 3, 5, 8
Change in leucocyte-C-reactive protein ratio
Time frame: Days 3, 5, 8
Change in the level of relative (%) number of lymphocytes of the general blood test
Time frame: Days 3, 5, 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2020.
- Individual participant dataSharing planned: No
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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.
Oksana A. Markova, MD study chair
AO GENERIUM
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tigerase® and best available care and Best available care in people with COVID-19 and Coronavirus Disease 2019, run by AO GENERIUM at 6 sites in Russia.
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 11 inclusion and 14 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 14 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Russia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The proportion of patients with mechanical ventilation (time frame: Day 8). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Oct 2020.