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

NCT04347239 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CD12_COVID-19
• Study Type: interventional
• Target: 484
• Locations: 1 country
• Sites: 18

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.

Conditions

Coronavirus Disease 2019

Keywords

COVID-19

Outcome Measures

Primary Outcomes (1)

• All-cause Mortality at Day 28

  Incidence of mortality at day 28

  Mortality at day 28 (Visit 2, start of treatment = day 0)

Secondary Outcomes (4)

• All-cause Mortality at Day 14

  Mortality at day 14 (initiation of treatment = day 0)

• 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

• Change in Clinical Status of Subjects at Day 28 (on a 7 Point Ordinal Scale)

  Change from start of treatment (baseline) to day 28

• Length of Hospital Stay

  Timeframe is from screening visit to end of treatment (visit 5)

Other Outcomes (1)

• All-Cause Mortality at Day 14 in the Critically Ill Population

  Mortality at day 14 (initiation of treatment = day 0)

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

700mg Leronlimab

EXPERIMENTAL

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.

Drug: Leronlimab (700mg)

700mg Leronlimab Open Label

EXPERIMENTAL

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.

Drug: Leronlimab (700mg)

Interventions

Placebo DRUG

Placebo

Placebo

Leronlimab (700mg) DRUG

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

Also known as: PRO 140

700mg Leronlimab; 700mg Leronlimab Open Label

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 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• CytoDyn, Inc.: lead

Study Sites (18)

Advanced Cardiovascular, LLC

Alexander City, Alabama, 35010, United States

Location

St. Jude Medical Center

Fullerton, California, 92835, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

James A. Haley Veterans' Hospital

Tampa, Florida, 33612, United States

Location

Center for Advanced Research & Education (CARE)

Gainesville, Georgia, 30501, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

St. Barnabas

Livingston, New Jersey, 07052, United States

Location

Atlantic Health System Hospital

Morristown, New Jersey, 07962-1905, United States

Location

Holy Name Medical Center

Teaneck, New Jersey, 07666, United States

Location

New York Community Hospital of Brooklyn

Brooklyn, New York, 11229, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Novant Health

Winston-Salem, North Carolina, 27103, United States

Location

Ohio Health

Columbus, Ohio, 43215, United States

Location

Good Samaritan Hospital Corvallis

Corvallis, Oregon, 97330, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

Baylor Scott & White Research Institute

Dallas, Texas, 75204, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 36427875 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

leronlimab

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

The outcome and safety data came from a report from the contract research organization that oversaw the study. A review of 64 Case Report Forms for the open label portion of the study indicated that over 70% contained no information about adverse events, therefore the adverse events for the open label portion of the study may be underreported.

Results Point of Contact

• Title: Bernie Cunningham, PhD, MRPharmS; VP Operations
• Organization: CytoDyn Inc.

bcunningham@cytodyn.com

5164060197

Study Officials

• Jacob Lalezari, MD

  CytoDyn, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Unblinded pharmacists at clinical sites were notified of the arm to which the subjects were enrolled for the randomized portion of the study in order to prepare the appropriate treatment. There was no masking for the open-label portion of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: There were 394 participants randomized to the blinded portion of the study using an Interactive Response Technology (IRT) system. A separate cohort of 90 new participants were enrolled in the open label portion of the study after completion of enrollment of the blinded portion. None of the participants involved in the blinded portion of the study were included in the open label portion.

Study Record Dates

• First Submitted: April 13, 2020
• First Posted: April 15, 2020
• Study Start: April 16, 2020
• Primary Completion: October 24, 2021
• Study Completion: June 15, 2022
• Last Updated: October 15, 2025
• Results First Posted: August 27, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)