Study of the Efficacy and Safety of Intravenous Pamrevlumab, in Hospitalized Participants With Acute COVID-19 Disease

Study Overview
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Brief Summary
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This study evaluates the efficacy and safety of intravenous (IV) infusions of pamrevlumab when compared with placebo in participants who are hospitalized with acute COVID-19 disease.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, phase 2, proof-of-concept study to evaluate the efficacy and safety of IV pamrevlumab, a monoclonal antibody, against connective-tissue growth factor (CTGF), in participants hospitalized with acute COVID-19 disease. All concomitant medications, including approved and non-approved treatments for COVID-19 (such as, hydroxychloroquine or interleukin 6 [IL-6] inhibitors), as well as supplemental oxygenation needs, will be collected and recorded. In addition, the following will be collected and recorded: documentation of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov-2) infection, documentation of any other infection(s) prior to or during hospitalization, and whether or not aggressive care is withheld or withdrawn, including the reason for withholding or withdrawal of care (such as a Do Not Resuscitate/Do Not Intubate [DNR/DNI] order or a resource limitation).

Official Title
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Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of the Efficacy and Safety of Intravenous Pamrevlumab, a Monoclonal Antibody Against Connective Tissue Growth Factor (CTGF), in Hospitalized Patients With Acute COVID-19 Disease

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Pamrevlumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed SARS-CoV-2 infection Respiratory compromise requiring hospitalization for COVID-19 disease as evidenced by at least one (or more) of the following criteria: Interstitial pneumonia on chest x-ray or high-resolution computed tomography (findings of consolidation or ground glass opacities), OR Peripheral capillary oxygen saturation < 94% on room air, OR Requiring non-invasive supplemental oxygen (such as, nasal cannula, face mask) to maintain SpO2 Not requiring mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) use at time of randomization Not participating in another clinical trial for the treatment of COVID-19 disease through Day 28 Exclusion Criteria: Female participants who are pregnant or nursing Participation in a clinical trial with another investigational drug for COVID-19 disease Anticipated discharge from the hospital or transfer to another hospital or long-term care facility which is not a study site within 72 hours of randomization History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Proof-of-concept
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pamrevlumab<br>Pamrevlumab: 35 milligrams/kilogram (mg/kg) on Days 1, 7, 14 and 28 for a total of 4 infusions over 4 weeks | Drug: Pamrevlumab<br>* Sterile liquid for injection<br>* Other names: FG-3019;|
| Experimental: Placebo<br>Pamrevlumab-matching placebo on Days 1, 7, 14 and 28 for a total of 4 infusions over 4 weeks | Drug: Placebo<br>* Sterile liquid for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Alive Who Never Received Mechanical Ventilation and/or Extracorporeal Membrane Oxygenation (ECMO) at Day 28 |  | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Alive, Discharged Home, and Not on Supplemental Oxygen at Day 28 |  | Day 28 | 
| Number of Participants Alive Who Never Received Mechanical Ventilation and/or ECMO at Day 14 |  | Day 14 | 
| Time to Recovery as Based on a Modified 8-Point Ordinal Scale | Recovery was defined as the first day on which the participant satisfied 1 of the following 3 categories from the 8-point ordinal scale: (1) hospitalized, not requiring supplemental oxygen; (2) Not hospitalized (discharged), but with limitation on activities and/or requiring home supplemental oxygen; (3) Not hospitalized (discharged), with no limitations on activities and not requiring supplemental oxygen). | Day 28 | 
| Days in Intensive Care Unit/Critical Care Unit (ICU/CCU) (Either on or Off Mechanical Ventilation and/or ECMO) | Days in ICU/CCU was calculated as Event end date/time - Event start data/time + 1. Participants who died in ICU/CCU before Day 28, days in ICU/CCU is calculated up to the death date. Days in ICU/CCU were censored after Day 28. | up to Day 28 | 
| Days on Mechanical Ventilation and/or ECMO | Days on Mechanical Ventilation and/or ECMO was calculated as Event end date/time - Event start data/time. Participants who died on MV/ECMO before Day 28, days on MV/ECMO is calculated up to the death date. Days on MV/ECMO are censored after Day 28. | up to Day 28 | 
| Time to Mechanical Ventilation/ECMO or All-cause Mortality | Time (number of days) from randomization to mechanical ventilation/ECMO or all-cause mortality by Day 28. Participants without the event are not included in the calculation. | up to Day 28 | 
| Number of Participants With All-cause Mortality |  | up to Day 28 | 
| Changes in Pressure of Arterial Oxygen to Fractional Inspired Oxygen Concentration (PaO2/FiO2) Ratio, Both as Categorical and Continuous Variables |  | up to Day 28 | 
| Time to Death From Any Cause | Time (number of days) from randomization to death from any cause by Day 28. Participants without the event are not included in the calculation. | up to Day 28 | 
| Change in Resting Peripheral Oxygen Saturation (SpO2) Adjusted by FiO2 |  | up to Day 28 | 
| Change in (Non-invasive) Oxygen Supplementation Requirements |  | up to Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe Acute Respiratory Syndrome coronavirus, SARS-COV-2 infection