Sarilumab for Patients With Moderate COVID-19 Disease

NCT04359901 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB 3305
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

Brief Summary

Objectives: To determine whether blockade of IL-6R is beneficial in patients with COVID-19 infection of moderate severity. Research Design: Randomized, controlled trial. Two-arm trial comparing standard care alone to standard care with addition of sarilumab (anti-IL6R). The trial will use a randomized play-the-winner design, in which randomization becomes weighted toward the arm that was more effective in previous subjects in the trial. Methodology Hospitalized patients meeting clinical criteria for moderate disease and testing positive for coronavirus infection. Interventions: sarilumab, 400 mg subcutaneous injection. Standard care is not pre-specified, may vary among patients, and may include agents with anti-viral activity, such as remdesivir or hydroxychloroquine, among others. Up to 120 patients, primary outcome intubation or death within 14 days. All data will be extracted remotely from the electronic health record (EHR). Clinical Implications: The study has potential to establish IL-6R blockade, delivered subcutaneously, as standard of care in reducing progression to critical illness in patients with moderate COVID-19 disease.

Conditions

COVID

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Intubation or Death

  Composite outcome of number of participants with intubation or death

  within 14 Days of enrollment

Study Arms (2)

Standard of care plus subcutaneous sarilumab

ACTIVE COMPARATOR

Standard of care as directed by the treating clinicians, plus sarilumab 400 mg subcutaneous injection. Sarilumab is provided in prefilled syringes/pens containing 200 mg each as is used clinically, and both injections will be given as soon as is convenient after the patient has decided to enroll.

Biological: SARILUMAB

Standard of care

NO INTERVENTION

Standard of care as directed by the treating clinicians.

Interventions

SARILUMAB BIOLOGICAL

Single dose of 400 mg subcutaneous sarilumab

Also known as: KEVZARA

Standard of care plus subcutaneous sarilumab

Eligibility Criteria

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

You may qualify if:

• Positive testing for novel coronavirus SARS-CoV-2019
• Patients with moderate COVID-19 disease as defined clinically:
• Score of 1-3 (out of 3) on a modified Brescia COVID respiratory severity score (BCRSS), elements of which include wheezing or inability to speak complete sentences without effort, respiratory rate ≥22, O2 saturation ≤ 94% with or without supplemental oxygen, or requiring ≥2L supplemental oxygen to maintain O2 Sat \>94% in patients without previously documented hypoxia or baseline oxygenation requirement; either is equal to one point on the score) all within a 24-hour period prior to enrollment, and/or any worsening of chest X-ray (CXR) findings after COVID-19 diagnosis
• Worsening of baseline oxygenation by at least 3%, or increase in oxygen requirement by at least 2L, in patients with pre-existing hypoxemia or receiving supplemental oxygen chronically.
• The BCRSS risk calculation score is available at: https://www.mdcalc.com/brescia-covid-respiratory-severity-scale-bcrss-algorithm

You may not qualify if:

• Critical disease, defined by need for mechanical ventilation
• Expected death within 48 hours
• Patients taking any of the following for chronic inflammatory diseases: glucocorticoids equivalent to prednisone \> 10 mg/day (methylprednisolone \> 8 mg/day, dexamethasone \> 2 mg/day), a JAK inhibitor (tofacitinib, baricitinib, upadacitinib), or a biologic
• Receipt of any IL-6 inhibitor within 3 months prior to enrollment in the trial
• Pregnancy, due to lack of fetal monitoring capabilities
• Patients enrolled in other interventional clinical trials, including for COVID-19. Patients enrolled in non-interventional studies or receiving non-FDA-approved drugs for compassionate use are not excluded.
• Patients whose goal of care is comfort measures only
• Inability to provide informed consent, or absence of a legally authorized representative to provide informed consent.
• Severe psychiatric disease that prevents compliance with typical medical care.
• Initial positive test for active infection with novel coronavirus SARS-CoV-2019 was \>4 weeks prior to current admission.

Sponsors & Collaborators

• Westyn Branch-Elliman: lead

Study Sites (5)

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Location

VA Maine Healthcare System

Augusta, Maine, 04330, United States

Location

VA Boston Healthcare System

Boston, Massachusetts, 02132, United States

Location

Providence VA Medical Center

Providence, Rhode Island, 02908, United States

Location

VA Medical Center - White River Junction

White River Junction, Vermont, 05009, United States

Location

Related Publications (6)

• Woods P, Flynn M, Monach P, Visnaw K, Schiller S, Holmberg E, Leatherman S, Ferguson R, Branch-Elliman W. Implementation of documented and written informed consent for clinical trials of communicable diseases: Lessons learned, barriers, solutions, future directions identified during the conduct of a COVID-19 clinical trial. Contemp Clin Trials Commun. 2021 Sep;23:100804. doi: 10.1016/j.conctc.2021.100804. Epub 2021 Jun 26.

  PMID: 34222708 BACKGROUND

• Dassum SR, Ferguson R, Woods P, Flynn M, Visnaw K, Holmberg E, Schiller S, Shannon C, Brophy M, Monach P, Leatherman S, Branch-Elliman W; VISN-1 Clinical Trials Network COVID-19 Investigators. Patient- reported reasons for non-participation in a COVID-19 therapeutics clinical trial: Findings from a multi-center investigation. Contemp Clin Trials. 2023 Mar;126:107082. doi: 10.1016/j.cct.2023.107082. Epub 2023 Jan 9.

  PMID: 36632925 BACKGROUND

• Dhond R, Acher R, Leatherman S, Page S, Sanford R, Elbers D, Meng F, Ferguson R, Brophy MT, Do NV. Rapid implementation of a modular clinical trial informatics solution for COVID-19 research. Inform Med Unlocked. 2021;27:100788. doi: 10.1016/j.imu.2021.100788. Epub 2021 Nov 12.

  PMID: 34786452 BACKGROUND

• Branch-Elliman W, Lehmann LS, Boden WE, Ferguson R, Monach P. Pragmatic, adaptive clinical trials: Is 2020 the dawning of a new age? Contemp Clin Trials Commun. 2020 Jul 17;19:100614. doi: 10.1016/j.conctc.2020.100614. eCollection 2020 Sep.

  PMID: 32724866 BACKGROUND

• Branch-Elliman W, Monach PA. Not What Anyone Signed up for: Unnecessary and Insurmountable Barriers Encountered in Conducting Clinical Trials in COVID-19. Narrat Inq Bioeth. 2021;11(1):8-15. doi: 10.1353/nib.2021.0003. No abstract available.

  PMID: 34334456 BACKGROUND

• Branch-Elliman W, Ferguson R, Doros G, Woods P, Leatherman S, Strymish J, Datta R, Goswami R, Jankowich MD, Shah NR, Taylor TH, Page ST, Schiller SJ, Shannon C, Hau C, Flynn M, Holmberg E, Visnaw K, Dhond R, Brophy M, Monach PA. Subcutaneous sarilumab for the treatment of hospitalized patients with moderate to severe COVID19 disease: A pragmatic, embedded randomized clinical trial. PLoS One. 2022 Feb 25;17(2):e0263591. doi: 10.1371/journal.pone.0263591. eCollection 2022.

  PMID: 35213547 RESULT

MeSH Terms

Interventions

sarilumab

Results Point of Contact

• Title: Westyn Branch-Elliman, MD, MMSc
• Organization: VA Boston Healthcare System

westyn.branch-elliman@va.gov

857-203-5116

Study Officials

• Westyn Branch-Elliman, MD

  VA Boston Healthcare System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine, Harvard Medical School; Investigator, VA Boston Center for Healthcare Organization and Implementation Research; Infectious Disease Consultant, VA Boston Healthcare System

Study Record Dates

• First Submitted: April 20, 2020
• First Posted: April 24, 2020
• Study Start: April 10, 2020
• Primary Completion: August 2, 2021
• Study Completion: August 2, 2021
• Last Updated: December 6, 2023
• Results First Posted: October 10, 2022

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Within one year of primary publication.
• Access Criteria: Consistent with VA Privacy, Regulatory and IT requirements and VHA Handbook 1200.12

Locations

US (5)