Safety and Efficacy of Dupilumab for Treatment of Hospitalized COVID-19 Patients

NCT04920916 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: HSR210184HSR220171
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled, superiority phase IIa trial to assess the safety and efficacy of dupilumab use in hospitalized patients with moderate to severe COVID-19 infection. Subsequently, we conducted a 1 year follow up study to investigate the occurrence of Post COVID conditions (PCC) in our study population through assessment of pulmonary function, symptoms, neurocognition and immune biomarkers to observe for any treatment group differences.

Conditions

COVID-19

Keywords

Anti-Inflammatory Agents

Outcome Measures

Primary Outcomes (2)

• Day 28 Ventilator Free Survival

  Proportion of patients alive and free of invasive mechanical ventilation

  at 28 Days ± 2d

• Follow up Study 1 Year Outcome: Pulmonary Function Testing- Oxygen Diffusion and 6 Minute Walk Testing

  Proportion of patients with abnormal diffusing capacity for carbon monoxide (DLCO) and/or 6 minute walk testing 1 year after acute COVID-19 infection.

  365 ± 90 days

Secondary Outcomes (18)

• Proportion of Patients With Eosinophilia

  Day 0 through Day 60

• Cumulative Incidence of Grade 3 and 4 Clinical Adverse Events, Serious Adverse Events (SAEs) or Death

  Day 0 through Day 60

• SARS-CoV-2 Variants

  Day 0

• Change in Plasma Total Immunoglobulin E (IgE) Levels

  Day 0 and Day 14

• Change in C-reactive Protein (CRP)

  Day 0 through Day 14

Study Arms (2)

Dupilimab

EXPERIMENTAL

Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.

Biological: Dupilumab

Placebo

PLACEBO COMPARATOR

Normal saline will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28.

Drug: Placebo

Interventions

Dupilumab BIOLOGICAL

Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.

Also known as: Dupixent

Dupilimab

Placebo DRUG

Normal Saline.

Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female 18 years of age or older at the time of enrollment.
• Patients hospitalized with a positive RT-PCR for SARS-CoV-2 within the last 14 days, with illness duration within the last 14 days, and evidence of moderate to severe COVID-19 infection as defined by NIH COVID-19 Severity Categorization (8):
• Moderate illness: Individuals who show evidence of lower respiratory disease during clinical assessment or imaging and who have saturation of oxygen SpO2≥ 94% on room air at sea level.
• Severe illness: Individuals who have SpO2 \<94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) \<300 mm Hg, respiratory frequency \>30 breaths/min, or lung infiltrates \>50%.
• Patient and/or legally authorized representative is willing and able to provide written informed consent and comply with all protocol requirements.
• Patients with hematologic malignancies or solid tumors are eligible.
• Patients with autoimmune disorders are eligible.
• Patients with immunodeficiency and organ or stem cell transplant recipients are eligible.
• Patients with acute or chronic renal injury/failure are eligible.
• Patients with neutropenia/lymphopenia are eligible.
• Patients with elevated liver function tests are eligible.
• Women who are not taking contraception are eligible.
• Patients who are currently or have recently received steroids and/or remdesivir are eligible.
• Patient agrees to not participate in another clinical trial for the treatment of COVID-19 through end of study period.

You may not qualify if:

• Patients who do not require inpatient admission for COVID-19 infection.
• Patients who require invasive mechanical ventilation at time of enrollment.
• A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk due to study participation.
• Pregnancy or breast feeding (lactating women who agree to discard breast milk from day 1 until two weeks after the last study product is given are not excluded).
• Allergy to Dupilumab or its excipients.
• Received any of the following in the two weeks prior to screening as treatment of COVID-19:
• small molecule tyrosine kinase inhibitors (e.g. imatinib, gefitinib, acalabrutinib, etc.);
• monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-interleukin-1 \[IL-1\], anti-IL-6 \[or sarilumab\], etc.);
• monoclonal antibodies targeting T-cells or B-cells as treatment for COVID-19;
• Any other immunomodulatory (other than steroids) medications within 5 half-lives or 30 days prior to randomization.
• Current acute parasitic helminth infection or history of chronic parasitic infection.
• History of ocular scleritis, uveitis, keratitis or recent (\<6 months) eye injury (chemical or traumatic), infection or vascular occlusion.
• Have received any live vaccine (that is, live attenuated) within 4 weeks before screening, or intend to receive a live vaccine (or live attenuated) during the study. Note: Use of non-live (inactivated) vaccinations is allowed for all subjects.

Sponsors & Collaborators

• University of Virginia: lead
• The Paul Manning Foundation: collaborator
• Virginia Catalyst: collaborator

Study Sites (1)

UVA Health

Charlottesville, Virginia, 22908, United States

Location

Related Publications (3)

• Sasson J, Donlan AN, Ma JZ, Haughey HM, Coleman R, Nayak U, Mathers AJ, Laverdure S, Dewar R, Jackson PEH, Heysell SK, Sturek JM, Petri WA Jr. Safety and Efficacy of Dupilumab for the Treatment of Hospitalized Patients With Moderate to Severe Coronavirus Disease 2019: A Phase 2a Trial. Open Forum Infect Dis. 2022 Jul 27;9(8):ofac343. doi: 10.1093/ofid/ofac343. eCollection 2022 Aug.

  PMID: 35959207 RESULT

• Hendrick J, Ma JZ, Haughey HM, Coleman R, Nayak U, Kadl A, Sturek JM, Jackson P, Young MK, Allen JE, Petri WA Jr. Pulmonary function and survival one year after dupilumab treatment of acute moderate to severe COVID-19: A follow up study from a Phase IIa trial. medRxiv [Preprint]. 2023 Sep 2:2023.09.01.23293947. doi: 10.1101/2023.09.01.23293947.

  PMID: 37693596 RESULT

• Sasson J, Donlan AN, Ma JZ, Haughey HM, Coleman R, Nayak U, Mathers AJ, Laverdure S, Dewar R, Jackson PEH, Heysell SK, Sturek JM, Petri WA Jr. Safety and Efficacy of Dupilumab for the Treatment of Hospitalized Patients with Moderate to Severe COVID 19: A Phase IIa Trial. medRxiv [Preprint]. 2022 May 19:2022.03.30.22273194. doi: 10.1101/2022.03.30.22273194.

  PMID: 35411349 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

dupilumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

This was a small study, designed as an early phase trial. Limitations included lack of achievement of the primary endpoint and the wide confidence intervals in the survival benefit of dupilumab at day 60. Additional limitations included unequal gender distribution between groups (also due to small sample size), patients were almost exclusively infected by the Delta variant of SARS CoV-2 and a higher-than-expected overall mortality rate.

Results Point of Contact

• Title: William Petri
• Organization: University of Virginia Health System

wap3g@virginia.edu

434-305-9633

Study Officials

• William A Petri Jr., MD, PhD

  University of Virginia Division of Infectious Disease

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Wade Hampton Frost Professor of Medicine and Vice Chair for Research of the Department of Medicine, and Professor of Medicine, Microbiology, Immunology and Cancer Biology, and Pathology, Medicine: Infectious Diseases and International Health

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 10, 2021
• Study Start: May 25, 2021
• Primary Completion: April 18, 2023
• Study Completion: April 18, 2023
• Last Updated: November 3, 2023
• Results First Posted: November 3, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)