Evaluate the Efficacy & Safety of Leronlimab in Patients With Severe or Critical COVID-19

Phase 2

Completed

Conditions: Coronavirus Disease 2019

Interventions: Drug: Placebo
Drug: Leronlimab (700mg)

Registration Number: NCT04347239

Lead Sponsor: CytoDyn, Inc.

Brief Summary: The purpose of this study was assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injection in subjects with severe or critical COVID-19 disease.

Detailed Description: This was a Phase 2b/3, two-arm, randomized, double blind, placebo controlled, adaptive design multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with severe or critical symptoms of respiratory illness caused by coronavirus 2019 infection. Patients will be randomized to receive weekly doses of 700 mg leronlimab (PRO 140), or placebo. Leronlimab (PRO 140) and placebo will be administered via subcutaneous injection.

A single arm, non-randomized, open-label phase was added to the protocol after completion of enrollment in the randomized phase of the study.

The study had three phases: Screening Period, Treatment Period, and Follow-Up Period.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 484

Inclusion Criteria

Male or female adult ≥ 18 years of age at time of screening.
Subjects hospitalized with severe or critical illness caused by coronavirus 2019 infection as defined below:

A. Severe Illness:

- Diagnosed with COVID-19 by standard reverse transcriptase polymerase chain reaction (RT-PCR) assay or equivalent testing within 5 days of screening

AND

Symptoms of severe systemic illness/infection with COVID-19:

- At least 1 of the following: fever, cough, sore throat, malaise, headache, muscle pain, shortness of breath at rest or with exertion, confusion, or symptoms of severe lower respiratory symptoms including dyspnea at rest or respiratory distress

AND

Clinical signs indicative of severe systemic illness/infection with COVID-19, with at least 1 of the following:

- respiration rate (RR) ≥ 30, heart rate (HR) ≥ 125, saturated oxygen (SaO2) <93% on room air or requires > 2L oxygen by nasal canula (NC) in order maintain SaO2 ≥93%, PaO2/FiO2 <300 (ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen)

AND

- None of the following: Respiratory failure (defined by endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, or clinical diagnosis of respiratory failure in setting of resource limitations), Septic shock (defined by systolic blood pressure (SBP) < 90 mm Hg, or Diastolic BP < 60 mm Hg), Multiple organ dysfunction/failure

B. Critical Illness:

- Diagnosed with COVID-19 by standard RT-PCR assay or equivalent testing within 5 days of screening

AND

Evidence of critical illness, defined by at least 1 of the following:

- Respiratory failure defined based on resource utilization requiring at least 1 of the following: Endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, extracorporeal membrane oxygenation (ECMO), or clinical diagnosis of respiratory failure (in setting of resource limitation)

OR

- Shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg or requiring vasopressors)

OR

-Multiple organ dysfunction/failure
Subject, if intubated, positive end expiratory pressure (PEEP) <15 cmH2O with PaO2/FiO2 >150 mmHg.
Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator
Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
Understands and agrees to comply with planned study procedures.
Women of childbearing potential and their partner must agree to use at least one highly effective method of contraception (e.g., hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], intrauterine devices, bilateral tubal occlusion, or sexual abstinence) for the duration of the study.

Exclusion Criteria

Subjects with do-not-resuscitate (DNR) and/or do-not-intubate (DNI) orders or expected to be made DNR/DNI in setting of resource limitations or family wishes.
Not a candidate for dialysis or continuation of care (or full medical support) in setting of resource limitations.
Subject on continuous vasopressors (at the dose of norepinephrine >20μg/min and/or vasopressin >0.04 units/kg/min) for >48 hours at time of screening.
Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible.
Inability to provide informed consent or to comply with test requirements
Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment
Pregnancy or breast feeding
Subject participating in another study with for an investigational treatment for COVID-19.

Note: Subject who were prescribed (1) hydroxychloroquine or chloroquine with or without azithromycin, (2) Remdesivir, (3) convalescent plasma therapy, or (4) immunomodulatory treatments (including but not limited to sarilumab, clazakizumab, tocilizumab, and anakinra) for the off-label treatment of COVID-19 prior to study enrollment may be included and may continue to receive these agents as part of standard-of-care.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo.
700mg Leronlimab	Leronlimab (700mg)	Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections.
700mg Leronlimab Open Label	Leronlimab (700mg)	Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections.

Primary Outcome Measures

Name	Time	Method
All-cause Mortality at Day 28	Mortality at day 28 (Visit 2, start of treatment = day 0)	Incidence of mortality at day 28

Secondary Outcome Measures

Name	Time	Method
All-cause Mortality at Day 14	Mortality at day 14 (initiation of treatment = day 0)	Day 0 refers to the data of randomization/first treatment.
Proportion of Patients Achieving a Category of 6 or Higher on the Ordinal Scale at Days 14 and 28 (on a 7 Point Ordinal Scale).	Change from baseline to days 14 and 28	Evaluation of the clinical status of participants at Day 28 was assessed with a 7-level ordinal scale (OS) (with higher score indicating better outcome). The OS of patient health status ranged from: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. The study enrolled hospitalized patients with an OS Score of 2, 3, or 4 at baseline. The OS score of 6 refers to a participant who is not hospitalized with limitation on activities and 7 refers to not hospitalized with no limitations on activities.
Change in Clinical Status of Subjects at Day 28 (on a 7 Point Ordinal Scale)	Change from start of treatment (baseline) to day 28	Evaluation of the clinical status of participants at Day 28 was assessed with a 7-level ordinal scale (OS) (with higher score indicating better outcome). The OS of patient health status ranged from: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. The study enrolled hospitalized patients with an OS Score of 2, 3, or 4 at baseline. Baseline is last available value before treatment. Change from baseline is based on patients with paired values. The p value is from rank ANCOVA model adjusted for stratification factor and age using imputed data. All results and change from baseline are based on the result of multiple imputation.
Length of Hospital Stay	Timeframe is from screening visit to end of treatment (visit 5)	Length of Hospital Stay measured in days

Trial Locations

Locations (18): Advanced Cardiovascular, LLC
🇺🇸
Alexander City, Alabama, United States
St. Jude Medical Center
🇺🇸
Fullerton, California, United States
UCLA
🇺🇸
Los Angeles, California, United States
James A. Haley Veterans' Hospital
🇺🇸
Tampa, Florida, United States
Center for Advanced Research & Education (CARE)
🇺🇸
Gainesville, Georgia, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
St. Barnabas
🇺🇸
Livingston, New Jersey, United States
Atlantic Health System Hospital
🇺🇸
Morristown, New Jersey, United States
Holy Name Medical Center
🇺🇸
Teaneck, New Jersey, United States
New York Community Hospital of Brooklyn
🇺🇸
Brooklyn, New York, United States
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Advanced Cardiovascular, LLC
🇺🇸Alexander City, Alabama, United States