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

NCT ID: NCT04347239

Last Updated: 2025-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 484 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-16
• Study Completion Date: 2022-06-15

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.

Conditions

Coronavirus Disease 2019

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

700mg Leronlimab

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.

Group Type: EXPERIMENTAL

Leronlimab (700mg)

Intervention Type: DRUG

Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)

700mg Leronlimab Open Label

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.

Group Type: EXPERIMENTAL

Leronlimab (700mg)

Intervention Type: DRUG

Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)

Interventions

Placebo

Placebo

Intervention Type: DRUG

Leronlimab (700mg)

Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)

Intervention Type: DRUG

Other Intervention Names

PRO 140

Eligibility Criteria

Inclusion Criteria

1. Male or female adult ≥ 18 years of age at time of screening.

2. 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

3. Subject, if intubated, positive end expiratory pressure (PEEP) <15 cmH2O with PaO2/FiO2 >150 mmHg.

4. Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator

5. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.

6. Understands and agrees to comply with planned study procedures.

7. 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

1. 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.

2. Not a candidate for dialysis or continuation of care (or full medical support) in setting of resource limitations.

3. 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.

4. Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible.

5. Inability to provide informed consent or to comply with test requirements

6. Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment

7. Pregnancy or breast feeding

8. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CytoDyn, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jacob Lalezari, MD

Role: STUDY_DIRECTOR

CytoDyn, Inc.

Locations

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

Montefiore Medical Center

The Bronx, New York, United States

Novant Health

Winston-Salem, North Carolina, United States

Ohio Health

Columbus, Ohio, United States

Good Samaritan Hospital Corvallis

Corvallis, Oregon, United States

Oregon Health and Sciences University

Portland, Oregon, United States

Baylor Scott & White Research Institute

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

University of Texas

Houston, Texas, United States

Countries

United States

References

Welch J, Dean J, Hartin J. Using NEWS2: an essential component of reliable clinical assessment. Clin Med (Lond). 2022 Nov;22(6):509-513. doi: 10.7861/clinmed.2022-0435.

Reference Type: BACKGROUND

PMID: 36427875 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

CD12_COVID-19

Identifier Type: -

Identifier Source: org_study_id