Clinical trial NCT04920916: Safety and Efficacy of Dupilumab for Treatment of Hospitalized COVID-19 Patients
Official title: Safety and Efficacy of the Treatment of Hospitalized Patients With COVID 19 Infection With an Inhibitor of IL-4 and IL-13 Signaling: A Phase IIa Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Keywords: Anti-Inflammatory Agents
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: The Paul Manning Foundation
name: Virginia Catalyst
First posted: 2021-06-10
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: A total of 40 eligible subject were enrolled and randomized in a 1:1 ratio to receive either dupilumab or placebo, stratifying on the disease severity measured by the required oxygen ≤ 15L or \> 15L by nasal cannula. Both arms received standard of care management per current National Institutes of Health (NIH) COVID-19 treatment guideline in addition to their randomized treatments. Patients were then followed prospectively for up to 360 days after enrollment.

As an extension to the randomized double-blind placebo-controlled trial assessing dupilumab for treatment of those hospitalized with acute moderate to severe COVID-19, subjects were followed up at 1 year for evaluation of pulmonary function testing (PFT), pulmonary imaging, immune biomarkers, neurocognition and symptoms.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Day 28 Ventilator Free Survival
timeFrame: at 28 Days ± 2d
measure: Follow up Study 1 Year Outcome: Pulmonary Function Testing- Oxygen Diffusion and 6 Minute Walk Testing
timeFrame: 365 ± 90 days
Secondary outcomes:
measure: Proportion of Patients With Eosinophilia
timeFrame: Day 0 through Day 60
measure: Cumulative Incidence of Grade 3 and 4 Clinical Adverse Events, Serious Adverse Events (SAEs) or Death
timeFrame: Day 0 through Day 60
measure: SARS-CoV-2 Variants
timeFrame: Day 0
measure: Change in Plasma Total Immunoglobulin E (IgE) Levels
timeFrame: Day 0 and Day 14
measure: Change in C-reactive Protein (CRP)
timeFrame: Day 0 through Day 14
measure: Change in Ferritin
timeFrame: Day 0 through Day 14
measure: Duration of Hospitalization
timeFrame: Day 0 through Day 30
measure: Day 60 All Cause Mortality
timeFrame: Day 60
measure: Day 28 All-cause Mortality Rate
timeFrame: at Day 28
measure: Day 60 Ventilator Free Survival
timeFrame: Day 60
measure: Percentage of Patients Needing Extracorporeal Membrane Oxygenation (ECMO)
timeFrame: Day 0 through Day 60
measure: Percentage of Patients Needing Renal Replacement Therapy
timeFrame: Day 0 through Day 60
measure: Percentage of Patients Needing Vasopressors
timeFrame: Day 0 through Day 60
measure: Follow Up Study 1 Year Outcome: All-cause Mortality at 1 Year
timeFrame: 365 days
measure: Follow-up Study 1 Year Outcome: Differences in High Resolution Computed Tomography (HRCT) Chest Scan Appearance Post Recovery
timeFrame: 365 ± 90 days
measure: Follow-up Study 1 Year Outcome: Conduct a 6 Minute Walk Testing
timeFrame: 365 ± 90 days
measure: Follow up Study 1 Year Outcome: Pulmonary Function Testing- Abnormal Spirometry
timeFrame: 365 ± 90 days
measure: Follow-up Study 1 Year Outcome: Assess Neurocognitive Function Using the MOCA
timeFrame: 365 ± 90 days
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: UVA Health
state: Virginia
Study officials:
affiliation: University of Virginia Division of Infectious Disease
name: William A Petri Jr., MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.