Study to Evaluate the Efficacy and Safety of Leronlimab for Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19)

A Phase 2b/3, Randomized, Double Blind, Placebo Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety of Leronlimab for Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Coronavirus Disease 2019
• Intervention / Treatment: Drug: Placebos; Drug: Leronlimab (700mg)

Detailed Description

This is 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 is added to the protocol after completion of enrollment in the Randomized Phase of the study.

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

• Study Type: Interventional
• Enrollment (Anticipated): 394
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Alexander City, Alabama, United States, 35010
      • Advanced Cardiovascular, LLC
  • California
    • Fullerton, California, United States, 92835
      • St. Jude Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA
  • Florida
    • Tampa, Florida, United States, 33612
      • James A. Haley Veterans' Hospital
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Center for Advanced Research & Education (CARE)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • New Jersey
    • Livingston, New Jersey, United States, 07052
      • St. Barnabas
    • Morristown, New Jersey, United States, 07962-1905
      • Atlantic Health System Hospital
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Brooklyn, New York, United States, 11229
      • New York Community Hospital of Brooklyn
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Ohio Health
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • Good Samaritan Hospital Corvallis
    • Portland, Oregon, United States, 97239
      • Oregon Health and Sciences University
  • Texas
    • Dallas, Texas, United States, 75204
      • Baylor Scott & White Research Institute
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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:

   - RR ≥ 30, HR ≥ 125, SaO2 <93% on room air or requires > 2L oxygen by NC in order maintain SaO2 ≥93%, PaO2/FiO2 <300

   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 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, 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 endexpiratory 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebos; Placebos
Experimental: 700mg Leronlimab	Drug: Leronlimab (700mg); Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality at Day 28	Day 0 refers to the data of randomization/first treatment.	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality at Day 14	Day 0 refers to the data of randomization/first treatment.	Day 14
Change in clinical status of subject at Day 14 (on a 7 point ordinal scale)	A 7-category ordinal scale of patient health status ranges 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.	Day 14
Change in clinical status of subject at Day 28 (on a 7 point ordinal scale)	A 7-category ordinal scale of patient health status ranges 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.	Day 28
Change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 14.	The SOFA score assessment will be based on PaO2/FiO2, platelets, Glasgow coma scale (GCS), bilirubin, Mean arterial pressure OR administration of vasoactive agents required, and Serum creatinine	Day 14

Collaborators and Investigators

• Sponsor: CytoDyn, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2020
• Primary Completion (Actual): October 24, 2021
• Study Completion (Anticipated): June 15, 2022

Study Registration Dates

• First Submitted: April 13, 2020
• First Submitted That Met QC Criteria: April 14, 2020
• First Posted (Actual): April 15, 2020

Study Record Updates

• Last Update Posted (Actual): January 14, 2022
• Last Update Submitted That Met QC Criteria: January 13, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Leronlimab
• Other Study ID Numbers: CD12_COVID-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No