Evaluation of the Efficacy and Safety of Sarilumab in Hospitalized Patients With COVID-19

NCT04315298 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 6R88-COV-2040
• Study Type: interventional
• Target: 1,912
• Locations: 1 country
• Sites: 62

Brief Summary

Phase 2: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 regardless of disease severity strata. Phase 3 Cohort 1: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with critical COVID-19 receiving mechanical ventilation at baseline. Phase 3 Cohort 2: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 receiving mechanical ventilation at baseline.

Conditions

COVID-19

Keywords

COVID-19; SARS-COV-2; coronavirus; IL-6; sarilumab; acute respiratory distress syndrome; treatment

Outcome Measures

Primary Outcomes (3)

• Percent Change From Baseline in CRP Levels at Day 4 in Participants With Serum IL-6 Level Greater Than the ULN (Phase 2)

  Percent Change from Baseline in C-Reactive Protein (CRP) Levels at Day 4 in Participants with Serum Interleukin 6 (IL-6) Level Greater than the Upper Limit of Normal (ULN) Least Squares (LS) means estimate of percent change from baseline at Day 4 (raw scale) for each treatment group is based on the Analysis of Covariance (ANCOVA) model. It is defined as anti-log of the estimate of dependent variable minus 1, i.e., (exp\[ln(CRP at day 4/Baseline CRP)\]-1. Negative numbers imply improvement in CRP.

  Baseline and Day 4

• Percentage of Participants With at Least a 1-point Improvement in Clinical Status From Baseline to Day 22 Using the 7-point Ordinal Scale in Participants With Critical COVID-19 Receiving Mechanical Ventilation at Baseline (Phase 3 Cohort 1)

  The ordinal scale is an assessment of the clinical status of a participant. The 7-point ordinal scale is as follows: 1\. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity

  Day 22

• Percentage of Participants With at Least 1-point Improvement in Clinical Status Using the 7-point Ordinal Scale in Participants With COVID-19 Receiving Mechanical Ventilation at Baseline (Phase 3 Cohort 2)

  The ordinal scale is an assessment of the clinical status of a participant The 7-point ordinal scale is as follows: 1\. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity

  Day 22

Secondary Outcomes (71)

• Time to Improvement (2 Points) in Clinical Status Assessment in Severe or Critical Patients With Serum IL-6 Levels Greater Than the Upper Limit of Normal (Phase 2)

  Up to Day 29

• Time to Improvement (2 Points) in Clinical Status Assessment in Severe or Critical Patients With All Serum IL-6 Levels (Phase 2)

  Up to Day 29

• Time to Resolution of Fever for at Least 48 Hours Without Antipyretics or Until Discharge, Whichever is Sooner, in Patients With Documented Fever at Baseline (Phase 2)

  Up to Day 29

• Time to Resolution of Fever for at Least 48 Hours Without Antipyretics by Clinical Severity (Phase 2)

  Up to day 29

• Time to Resolution of Fever for at Least 48 Hours Without Antipyretics or Until Discharge, Whichever is Sooner, by Baseline IL-6 Levels (Phase 2)

  Up to Day 29

Study Arms (6)

Sarilumab 200mg IV (P2)

EXPERIMENTAL

Phase 2

Drug: Sarilumab; Drug: Placebo

Sarilumab 200mg IV (P3:C1)

EXPERIMENTAL

Phase 3: Cohort 1

Drug: Sarilumab; Drug: Placebo

Sarilumab 400mg IV (P2)

EXPERIMENTAL

Phase 2

Drug: Sarilumab; Drug: Placebo

Sarilumab 400mg IV (P3:C1)

EXPERIMENTAL

Phase 3: Cohort 1

Drug: Sarilumab; Drug: Placebo

Sarilumab 800mg IV (P3:C2)

EXPERIMENTAL

Phase 3: Cohort 2

Drug: Sarilumab; Drug: Placebo

Sarilumab 800mg IV (P3: C3)

EXPERIMENTAL

Phase 3: Cohort 3

Drug: Sarilumab; Drug: Placebo

Interventions

Sarilumab DRUG

Single or multiple intravenous (IV) doses of sarilumab. Additional doses may be administered if the patient meets protocol defined criteria.

Also known as: Kevzara®, REGN88, SAR153191

Sarilumab 200mg IV (P2); Sarilumab 200mg IV (P3:C1); Sarilumab 400mg IV (P2); Sarilumab 400mg IV (P3:C1); Sarilumab 800mg IV (P3: C3); Sarilumab 800mg IV (P3:C2)

Placebo DRUG

Single or multiple intravenous (IV) doses of placebo to match sarilumab administration

Sarilumab 200mg IV (P2); Sarilumab 200mg IV (P3:C1); Sarilumab 400mg IV (P2); Sarilumab 400mg IV (P3:C1); Sarilumab 800mg IV (P3: C3); Sarilumab 800mg IV (P3:C2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR), result from any specimen (or other commercial or public health assay) within 2 weeks prior to randomization and no alternative explanation for current clinical condition
• Hospitalized with illness of any duration with evidence of pneumonia, requires supplemental oxygen and/or assisted ventilation and meets one of the following:
• Phase 2 and Phase 3 Cohort 1:
• Meets 1 of the following criteria at baseline:
• Severe disease OR
• Critical disease OR
• Multi-system organ dysfunction OR
• Immunocompromised
• Phase 3 Cohort 2:
• Patients must be receiving mechanical ventilation to treat respiratory failure due to COVID-19
• Phase 3 Cohort 3:
• Patients must be receiving supplemental oxygen to treat hypoxemia delivered by one of the following devices:
• Non-rebreather mask, OR
• High-flow device with at least 50% FiO2, OR
• Non-invasive positive pressure ventilator

You may not qualify if:

• In the opinion of the investigator, not expected to survive for more than 48 hours from screening
• Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 2000 mm3, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 5 x upper limit of normal (ULN), platelets \<50,000 per mm3
• Treatment with anti-IL 6, anti-IL-6R antagonists, or with Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period
• Current treatment with the simultaneous combination of leflunomide and methotrexate
• Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections
• Participation in a double-blind clinical research study evaluating an investigational product (IP) or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit (The use of remdesivir, hydroxychloroquine, or other treatments being used for COVID-19 treatments in the context of an open-label study, Emergency Use Authorization (EUA), compassionate use protocol or open-label use is permitted)
• Any physical examination findings, and/or history of any illness, concomitant medications or recent live vaccines that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study
• Known systemic hypersensitivity to sarilumab or the excipients of the drug product
• Phase 3 Cohort 2 and Cohort 3 only:
• Known or suspected history of immunosuppression or immunodeficiency disorder
• Patients who require renal replacement therapy for acute kidney injury at randomization or who required renal replacement therapy within 72 hours prior to randomization
• Patients who have circulatory shock requiring vasopressors at randomization or within 24 hours prior to randomization
• Use of extracorporeal life support (eg, ECMO) or, in the opinion of the investigator, there is a high likelihood that extracorporeal life support will be initiated within 48 hours after randomization

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (62)

Regeneron Study Site

Los Angeles, California, 90095, United States

Location

Regeneron Study Site

Sacramento, California, 95817, United States

Location

Regeneron Study Site

Santa Monica, California, 90404, United States

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Regeneron Study Site

Aurora, Colorado, 80045, United States

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Regeneron Study Site

Denver, Colorado, 80206, United States

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Regeneron Study Site

New Haven, Connecticut, 06520, United States

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Regeneron Study Site

Washington D.C., District of Columbia, 20010, United States

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Regeneron Study Site

Gainesville, Florida, 32610, United States

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Regeneron Study Site

Orlando, Florida, 32803, United States

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Regeneron Study Site

Tampa, Florida, 33606, United States

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Atlanta, Georgia, 30322, United States

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Regeneron Study Site

Decatur, Georgia, 30033, United States

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Regeneron Study Site

Marietta, Georgia, 30060, United States

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Regeneron Study Site

Chicago, Illinois, 60611, United States

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Regeneron Study Site

Chicago, Illinois, 60612, United States

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Regeneron Study Site

New Orleans, Louisiana, 70112, United States

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Regeneron Study Site

Boston, Massachusetts, 02111, United States

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Regeneron Study Site

Boston, Massachusetts, 02114, United States

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Regeneron Study Site

Boston, Massachusetts, 02215, United States

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Regeneron Study Site

Ann Arbor, Michigan, 48109, United States

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Regeneron Study Site

Rochester, Minnesota, 55905, United States

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Regeneron Study Site

Edison, New Jersey, 08820, United States

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Regeneron Study Site

Hackensack, New Jersey, 07601, United States

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Regeneron Study Site

Livingston, New Jersey, 07039, United States

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Regeneron Study Site

Morristown, New Jersey, 07960, United States

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Regeneron Study Site

Neptune City, New Jersey, 07753, United States

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Regeneron Study Site

Newark, New Jersey, 07112, United States

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Regeneron Study Site

Teaneck, New Jersey, 07666, United States

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Regeneron Study Site

Brooklyn, New York, 11219, United States

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Regeneron Study Site

Buffalo, New York, 14263, United States

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Regeneron Study Site

Elmhurst, New York, 11373, United States

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Regeneron Study Site 1

Manhasset, New York, 11030, United States

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Regeneron Study Site 2

Manhasset, New York, 11030, United States

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Regeneron Study Site

New York, New York, 10003, United States

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Regeneron Study Site

New York, New York, 10016, United States

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Regeneron Study Site 1

New York, New York, 10025, United States

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Regeneron Study Site 2

New York, New York, 10025, United States

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Regeneron Study Site

New York, New York, 10029, United States

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Regeneron Study Site

New York, New York, 10032, United States

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Regeneron Study Site

New York, New York, 10037, United States

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Regeneron Study Site

New York, New York, 10065, United States

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Regeneron Study Site

New York, New York, 10075, United States

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Regeneron Study Site

Stony Brook, New York, 11794, United States

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Regeneron Study Site

The Bronx, New York, 10451, United States

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Regeneron Study Site 1

The Bronx, New York, 10461, United States

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Regeneron Study Site 2

The Bronx, New York, 10461, United States

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Regeneron Study Site

The Bronx, New York, 10467, United States

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Regeneron Study Site

Valhalla, New York, 10595, United States

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Regeneron Study Site

Tulsa, Oklahoma, 74104, United States

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Regeneron Study Site

Portland, Oregon, 97213, United States

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Regeneron Study Site

Portland, Oregon, 97239, United States

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Regeneron Study Site

Danville, Pennsylvania, 17822, United States

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Regeneron Study Site

Philadelphia, Pennsylvania, 19140, United States

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Regeneron Study Site

Scranton, Pennsylvania, 18510, United States

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Regeneron Study Site

Wilkes-Barre, Pennsylvania, 18711, United States

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Regeneron Study Site

Dallas, Texas, 75246, United States

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Regeneron Study Site

Dallas, Texas, 75390, United States

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Regeneron Study Site

Murray, Utah, 84107, United States

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Regeneron Study Site

Falls Church, Virginia, 22042, United States

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Regeneron Study Site

Richmond, Virginia, 23298, United States

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Regeneron Study Site

Everett, Washington, 98201, United States

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Regeneron Study Site

Renton, Washington, 98055, United States

Location

Related Publications (3)

• Devalaraja-Narashimha K, Ehmann PJ, Huang C, Ruan Q, Wipperman MF, Kaplan T, Liu C, Afolayan S, Glass DJ, Mellis S, Yancopoulos GD, Hamilton JD, MacDonnell S, Hamon SC, Boyapati A, Morton L. Association of complement pathways with COVID-19 severity and outcomes. Microbes Infect. 2023 May;25(4):105081. doi: 10.1016/j.micinf.2022.105081. Epub 2022 Dec 7.

  PMID: 36494054 DERIVED

• Sivapalasingam S, Lederer DJ, Bhore R, Hajizadeh N, Criner G, Hosain R, Mahmood A, Giannelou A, Somersan-Karakaya S, O'Brien MP, Boyapati A, Parrino J, Musser BJ, Labriola-Tompkins E, Ramesh D, Purcell LA, Gulabani D, Kampman W, Waldron A, Ng Gong M, Saggar S, Sperber SJ, Menon V, Stein DK, Sobieszczyk ME, Park W, Aberg JA, Brown SM, Kosmicki JA, Horowitz JE, Ferreira MA, Baras A, Kowal B, Thomas DiCioccio A, Akinlade B, Nivens MC, Braunstein N, Herman GA, Yancopoulos GD, Weinreich DM. Efficacy and Safety of Sarilumab in Hospitalized Patients With Coronavirus Disease 2019: A Randomized Clinical Trial. Clin Infect Dis. 2022 Aug 24;75(1):e380-e388. doi: 10.1093/cid/ciac153.

  PMID: 35219277 DERIVED

• Boyapati A, Wipperman MF, Ehmann PJ, Hamon S, Lederer DJ, Waldron A, Flanagan JJ, Karayusuf E, Bhore R, Nivens MC, Hamilton JD, Sumner G, Sivapalasingam S. Baseline Severe Acute Respiratory Syndrome Viral Load Is Associated With Coronavirus Disease 2019 Severity and Clinical Outcomes: Post Hoc Analyses of a Phase 2/3 Trial. J Infect Dis. 2021 Dec 1;224(11):1830-1838. doi: 10.1093/infdis/jiab445.

  PMID: 34496013 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; Respiratory Distress Syndrome

Interventions

sarilumab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Results Point of Contact

• Title: Clinical Trials Adminstrator
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2020
• First Posted: March 19, 2020
• Study Start: March 18, 2020
• Primary Completion: July 24, 2020
• Study Completion: September 2, 2020
• Last Updated: September 23, 2021
• Results First Posted: September 23, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification
• Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, EMA, PMDA, etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).

Locations

US (62)