COVID19Early Phase 1NCT04386239
Study on the Use of Sarilumab in Patients With COVID-19 Infection
A Early Phase 1 study testing Sarilumab Prefilled Syringe in people with COVID19, run by ASST Fatebenefratelli Sacco at 1 site in Italy.
Trial summary
Sarilumab is an anti-interleukin-6 human monoclonal antibody, such as tocilizumab, which is administered subcutaneously every two weeks for the treatment of moderate to severe active rheumatoid arthritis in adult patients. Read more about this study
- Who is it for?
- Ages 18 to 84 years
- Conditions the study is for
- COVID19
- What is being tested?
- Sarilumab Prefilled Syringe
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jan 2021to 1 Jan 2023
- Phase
- Early Phase 1
- 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 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years and < 85 years.
- Documented (chest X-Ray or TC scan), severe (BCRSS ≥3 and <4) interstitial pneumonia with respiratory failure (requiring supplemental oxygen) with positive Covid-19 swab testing.
- Worsening of respiratory exchanges such as to require ventilation with Venturi mask >31% (6L/minute).
- Increased levels of D-dimer (> 1500 ng/mL) or D-dimer progressively increasing (over 3 consecutive measurements) and reaching ≥ 1000 ng/mL.
- Signed informed consent.
Who cannot join
- Age < 18 years or ≥ 85 years.
- AST / ALT > 5x Upper normal limit.
- Neutrophil count lower than 500 cells / mL.
- Platelet count lower than 50,000 cells / mL.
- Documented sepsis due to infections other than Covid-19.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Divisione Clinicizzata di Malattie Infettive, ASST FBF-Sacco
Milan, MI, 20157
About this study
Official title: Pilot Study on the Use of Sarilumab in Patients With COVID-19 Infection
Sarilumab is an anti-interleukin-6 human monoclonal antibody, such as tocilizumab, which is administered subcutaneously every two weeks for the treatment of moderate to severe active rheumatoid arthritis in adult patients. Despite the effectiveness reported for tocilizumab in the recently published experiences, the need to rapidly find alternative therapies to manage the complications of Covid-19 infection remains extremely high. The lack of clinical experience on the usage of sarilumab in such patients prevents the possibility of adopting early access programs for using commercially available sarilumab (prefilled syringe) packs in patients with severe Covid-19 pneumonia. The present study is aimed to generate a rapid, still robustly documented, evidence on the potential clinical efficacy and tolerability of a further IL-6R antagonist in Covid-19 pneumonia.
Read the detailed description
In February 2020, the emergence of the COVID-19 epidemic in Italy and, especially, in Lombardy, with a potential fatal outcome in a significant proportion of cases, determined the need for adopting new therapeutic approached based on the few data available in literature. Although there are no clinical data available in COVID-19 patients concomitantly treated with Sarilumab subcutaneously (SC) nor intravenously (IV), there is scientific rationale that supports the exploration of sarilumab to treat pulmonary complications related to Covid-195-6. By inhibiting interleukin-6 (IL-6)signaling, sarilumab may potentially interrupt cytokine-mediated pulmonary injury precipitated by infection with SARS-CoV-2 and thereby ameliorate severity and/or reduce mortality among patients presenting with Covid-19 pneumonia when administered in conjunction with antiviral therapy. given the apparent dose/dose pharmacokinetic/ pharmacodynamic (PK/PD) equivalence of 400 mg of tocilizumab to 400 mg of sarilumab, we propose a dose escalation protocol by which the first 5 included patients will be treated with a dosage of 200 mg of sarilumab IV as 1st dose, followed by clinical reassessment after 12 hours and in case of no major adverse events and lack of improvement in respiratory function and / or persistence of fever and persistently high inflammatory markers re-administration of 200 mg intravenous (IV) of sarilumab. If no patients showed unfavorable safety signals, and no clear improvement is detected in >50% of the initially treated five patients after 96 hours since last administration, the dosage will be increase to sarilumab 400 mg IV as first and second dose in the remaining patients.
- Conditions
- COVID19
- Being tested
- Sarilumab Prefilled Syringe
- Keywords
- Coronavirus, Pandemic, Lombardy
- Medical subject headings
- COVID-19, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sarilumab Prefilled SyringeDrug
Also called Sarilumab
Sarilumab administration must be associated with an antiviral treatment as defined by the treatment protocol suggested by the SIMET Experts group 4 and AIFA recommendations: chloroquine 500 mg 1 tablet twice daily or hydroxychloroquine 400 mg 1 tablet twice daily in the first day and then 200 mg 1 tablet twice daily.
| Study group | Role | What they receive |
|---|---|---|
| Covid-19 | Experimental | Patients with documented (chest X-Ray or Computed Tomography scan) Covid-19 (Polymerase Chain Reaction+ swab test) interstitial pneumonia and BCRSS ≥3 and <4 will be requested consent to the study. Receives: Drug: Sarilumab Prefilled Syringe |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients who show an improvement of the respiratory function
Clinical efficacy of sarilumab in adult patients hospitalized due to severe Covid-19 pneumonia based on the proportion of patients who show an improvement of the respiratory function, described as ≥30% decrease in oxygen requirement compared to baseline (as defined as the ratio of O2 flow through the Venturi mask).
Measured: 6 weeks
Secondary outcomes (6)
Evaluation of the time to resolution of fever
Evaluation of the time to resolution of fever, defined as body temperature ≤36.6°C axilla, ≤37.8°C rectal or tympanic for at least 48 hours without antipyretics in patients with fever at baseline.
Measured: 6 weeks
Evaluation of the viral load on blood and sputum for COVID-19
Evaluation of the viral load on blood and sputum for COVID-19
Measured: Before administration of sarilumab, 48 hours and 96 hours after administration
Evaluation of the plasma concentration of GM-CSF
Evaluation of the plasma concentration of GM-CSF
Measured: Pre-treatment and 96 and 120 hours post-treatment
Evaluation of the plasma concentration of Il-6
Evaluation of the plasma concentration of Il-6
Measured: Pre-treatment and 96 and 120 hours post-treatment
Evaluation of the plasma concentration of TNF-α
Evaluation of the plasma concentration of TNF-α
Measured: Pre-treatment and 96 and 120 hours post-treatment
Evaluation of the rate of progression of White Blood Cell (WBC) fraction
Evaluation of the rate of progression of WBC fraction of immature granulocytes - IG - (absolute count).
Measured: 96 and 120 hours post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2020
- Study start1 Jan 2021
- Primary completion1 Jan 2023
- Study completion1 Jan 2023
Why it stopped: Technical impasse from IRB
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID19Studies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Monocentric, escalation dose
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- ASST Fatebenefratelli Sacco
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stefano Rusconi, ASST Fatebenefratelli Sacco
- Investigators
- Massimo Galli, Professor, Principal investigator, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04386239
- Sponsor's protocol ID
- COVID-SARI-001
- Status last verified
- Feb 2023
- First submitted
- 7 May 2020
- Last updated
- 3 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- 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 3 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study on the Use of Sarilumab in Patients With COVID-19 Infection
- ClinicalTrials.gov ID
- NCT04386239
- Acronym / sponsor ID
- COVID-SARI-001
- Conditions
- COVID19
- Keywords
- Coronavirus, Pandemic, Lombardy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Technical impasse from IRB
- Enrolment
- 0 participants (actual)
- Lead sponsor
- ASST Fatebenefratelli SaccoUniversity, hospital or other
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 1 Jan 2023 (actual)
- Study completion
- 1 Jan 2023 (actual)
- First posted
- 13 May 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.
Sarilumab is an anti-interleukin-6 human monoclonal antibody, such as tocilizumab, which is administered subcutaneously every two weeks for the treatment of moderate to severe active rheumatoid arthritis in adult patients. Despite the effectiveness reported for tocilizumab in the recently published experiences, the need to rapidly find alternative therapies to manage the complications of Covid-19 infection remains extremely high. The lack of clinical experience on the usage of sarilumab in such patients prevents the possibility of adopting early access programs for using commercially available sarilumab (prefilled syringe) packs in patients with severe Covid-19 pneumonia. The present study is aimed to generate a rapid, still robustly documented, evidence on the potential clinical efficacy and tolerability of a further IL-6R antagonist in Covid-19 pneumonia.
Detailed description
In February 2020, the emergence of the COVID-19 epidemic in Italy and, especially, in Lombardy, with a potential fatal outcome in a significant proportion of cases, determined the need for adopting new therapeutic approached based on the few data available in literature. Although there are no clinical data available in COVID-19 patients concomitantly treated with Sarilumab subcutaneously (SC) nor intravenously (IV), there is scientific rationale that supports the exploration of sarilumab to treat pulmonary complications related to Covid-195-6. By inhibiting interleukin-6 (IL-6)signaling, sarilumab may potentially interrupt cytokine-mediated pulmonary injury precipitated by infection with SARS-CoV-2 and thereby ameliorate severity and/or reduce mortality among patients presenting with Covid-19 pneumonia when administered in conjunction with antiviral therapy. given the apparent dose/dose pharmacokinetic/ pharmacodynamic (PK/PD) equivalence of 400 mg of tocilizumab to 400 mg of sarilumab, we propose a dose escalation protocol by which the first 5 included patients will be treated with a dosage of 200 mg of sarilumab IV as 1st dose, followed by clinical reassessment after 12 hours and in case of no major adverse events and lack of improvement in respiratory function and / or persistence of fever and persistently high inflammatory markers re-administration of 200 mg intravenous (IV) of sarilumab. If no patients showed unfavorable safety signals, and no clear improvement is detected in >50% of the initially treated five patients after 96 hours since last administration, the dosage will be increase to sarilumab 400 mg IV as first and second dose in the remaining patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Monocentric, escalation dose
| Arm | Type | Receives |
|---|---|---|
| Covid-19 | Experimental | Drug: Sarilumab Prefilled SyringePatients with documented (chest X-Ray or Computed Tomography scan) Covid-19 (Polymerase Chain Reaction+ swab test) interstitial pneumonia and BCRSS ≥3 and <4 will be requested consent to the study. |
Who may qualify
- Ages
- 18 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 years and < 85 years.
- Documented (chest X-Ray or TC scan), severe (BCRSS ≥3 and <4) interstitial pneumonia with respiratory failure (requiring supplemental oxygen) with positive Covid-19 swab testing.
- Worsening of respiratory exchanges such as to require ventilation with Venturi mask >31% (6L/minute).
- Increased levels of D-dimer (> 1500 ng/mL) or D-dimer progressively increasing (over 3 consecutive measurements) and reaching ≥ 1000 ng/mL.
- Signed informed consent.
Key exclusion criteria (5 listed)
- Age < 18 years or ≥ 85 years.
- AST / ALT > 5x Upper normal limit.
- Neutrophil count lower than 500 cells / mL.
- Platelet count lower than 50,000 cells / mL.
- Documented sepsis due to infections other than Covid-19.
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 |
|---|---|---|
| Sarilumab Prefilled SyringeAlso: SarilumabSarilumab administration must be associated with an antiviral treatment as defined by the treatment protocol suggested by the SIMET Experts group 4 and AIFA recommendations: chloroquine 500 mg 1 tablet twice daily or hydroxychloroquine 400 mg 1 tablet twice daily in the first day and then 200 mg 1 tablet twice daily. | Drug | Covid-19 |
Primary outcome
Proportion of patients who show an improvement of the respiratory function
Time frame: 6 weeks
Clinical efficacy of sarilumab in adult patients hospitalized due to severe Covid-19 pneumonia based on the proportion of patients who show an improvement of the respiratory function, described as ≥30% decrease in oxygen requirement compared to baseline (as defined as the ratio of O2 flow through the Venturi mask).
6 secondary outcomes
Evaluation of the time to resolution of fever
Time frame: 6 weeks
Evaluation of the viral load on blood and sputum for COVID-19
Time frame: Before administration of sarilumab, 48 hours and 96 hours after administration
Evaluation of the plasma concentration of GM-CSF
Time frame: Pre-treatment and 96 and 120 hours post-treatment
Evaluation of the plasma concentration of Il-6
Time frame: Pre-treatment and 96 and 120 hours post-treatment
Evaluation of the plasma concentration of TNF-α
Time frame: Pre-treatment and 96 and 120 hours post-treatment
Evaluation of the rate of progression of White Blood Cell (WBC) fraction
Time frame: 96 and 120 hours post-treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2023.
- 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.
Massimo Galli, Professor principal investigator
University of Milan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Sarilumab Prefilled Syringe in people with COVID19, run by ASST Fatebenefratelli Sacco at 1 site in Italy.
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 5 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: withdrawn, as of the sponsor's last update on 3 Feb 2023. 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 Italy. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 was withdrawn before enrolling participants, so there are no results.
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?
Proportion of patients who show an improvement of the respiratory function (time frame: 6 weeks). 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 3 Feb 2023.