Study to Evaluate the Efficacy and Safety of Leronlimab for Mild to Moderate COVID-19

A Phase 2, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Leronlimab for Mild to Moderate Coronavirus Disease 2019 (COVID-19)

This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection.

Study Overview

• Status: Completed
• Conditions: Coronavirus Disease 2019
• Intervention / Treatment: Drug: Placebo; Drug: Leronlimab (700mg)

Detailed Description

This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate 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.

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

A total of 75 subjects will be randomized 2:1 in this study.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • Palm Springs, California, United States, 92262-4871
      • Palmtree Clinical Research, Inc.
    • Rancho Mirage, California, United States, 92270
      • Eisenhower Health
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale
  • 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
    • Morristown, New Jersey, United States, 07962-1905
      • Atlantic Health System Hospital
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • White Plains, New York, United States, 10601
      • White Plains Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 27103
      • Novant Health
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Ohio Health
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (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 enrollment.

2. Subjects with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection as defined below:

   Mild (uncomplicated) Illness:

   • Diagnosed with COVID-19 by a standardized RT-PCR assay AND
   • Mild symptoms, such as fever, rhinorrhea, mild cough, sore throat, malaise, headache, muscle pain, or malaise, but with no shortness of breath AND
   • No signs of a more serious lower airway disease AND
   • RR<20, HR <90, oxygen saturation (pulse oximetry) > 93% on room air

   Moderate Illness:

   • Diagnosed with COVID-19 by a standardized RT-PCR assay AND
   • In addition to symptoms above, more significant lower respiratory symptoms, including shortness of breath (at rest or with exertion) OR
   • Signs of moderate pneumonia, including RR ≥ 20 but <30, HR ≥ 90 but less than 125, oxygen saturation (pulse oximetry) > 93% on room air AND
   • If available, lung infiltrates based on X-ray or CT scan < 50% present
3. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.
4. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
5. Understands and agrees to comply with planned study procedures.
6. Women of childbearing potential must agree to use at least one medically accepted method of contraception (e.g., barrier contraceptives [condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], or intrauterine devices) for the duration of the study.

Exclusion Criteria:

1. Subjects showing signs of acute respiratory distress syndrome (ARDS) or respiratory failure necessitating mechanical ventilation at the time of screening;
2. History of severe chronic respiratory disease and requirement for long-term oxygen therapy;
3. Subjects showing signs of clinical jaundice at the time of screening;
4. History of moderate and severe liver disease (Child-Pugh score >12);
5. Subjects requiring Renal Replacement Therapy (RRT) at the time of screening;
6. History of severe chronic kidney disease or requiring dialysis;

7. Any uncontrolled active systemic infection requiring admission to an intensive care unit (ICU); Note: Subjects infected with chronic hepatitis B virus or hepatitis C virus will be eligible for the study if they have no signs of hepatic decompensation.

   Note: Subjects infected with HIV-1 will be eligible for the study with undetectable viral load and are on a stable ART regimen. Investigators are required to review the subjects' medical records to confirm HIV-1 RNA suppression within the previous 3 months.

   Note: Empirical antibiotic treatment for secondary bacterial infections is allowed during the course of study.

8. Patients with malignant tumor, or other serious systemic diseases;
9. Patients who are participating in other clinical trials;
10. Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible; and
11. Inability to provide informed consent or to comply with test requirements

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; The placebo comparator consists of the formulation buffer for leronlimab, i.e., the placebo is the same as the active arm without leronimab. The placebo is presented in the same container closure at the same fill volume as the active (nominal 1mL fill volume). The formulation buffer contains histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections.	Drug: Placebo; Placebo
Experimental: 700mg Leronlimab; Each vial of active contains 175mg of leronlimab at a concentration of 175mg/ml (nominal 1mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections.	Drug: Leronlimab (700mg); Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5); Other Names: PRO 140

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Total Symptom Score	Clinical Improvement as assessed by change in total symptom score (for fever, myalgia, dyspnea and cough) by count of patients showing improvement, no change or worsened. Note: The total score per patient ranges from 0 to 12 points. Each symptom is graded from 0 to 3. [0=none, 1=mild, 2=moderate, and 3=severe]. Higher scores mean a worse outcome. A negative change from baseline shows an improvement in symptom score.	Clinical Improvement will be assessed at baseline and at EOT (day 14).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Clinical Resolution (TTCR)	Defined as the time from initiation of study treatment to the resolution of clinical symptoms (fever, myalgia, dyspnea, cough). Data presented how the number of days at which a certain percentage of patients achieve resolution of symptoms, i.e., 50% of patients on placebo saw resolution of symptoms in 15 days, and 15 days for patients on leronlimab. The hazard ratio was 0.781, 95% Confidence Interval 0.43, 1.41 and the p-value was 0.4138. TTCR is defined as the duration from date of first exposure to treatment to the first occurrence of total symptom score equals 0.	Time (in days) from initiation of study treatment until resolution of clinical symptoms (fever, myalgia, dyspnea and cough).
Incidence of Hospitalization	Number of patients requiring hospitalization	From visit 2 (day 0) through day 14 (in days)
Duration (Days) of Hospitalization	Duration of hospitalization in days	Total duration of hospitalization between visit 2 (day 0) in days and end of treatment
Incidence of Mechanical Ventilation	Incidence of mechanical ventilation supply	Total duration of mechanical ventilation since visit 2 (day 0) (days)
Duration of Mechanical Ventilation Supply	Duration (days) of mechanical ventilation supply	Duration of mechanical ventilation since visit 2 (day 0) (days
Incidence of Oxygen Use	Incidence of oxygen use over course of treatment	Use of oxygen since visit 2 (day 0) to end of treatment
Duration of Oxygen Use	Duration of oxygen use in days	Total duration of oxygen use since visit 2 (day 0) to EOT (day 14) (days)
Mortality at Day 14	Incidence of mortality at day 14	Mortality at EOT (day 14)
Time to Return to Normal Activity	Time to return to normal activity from initiation of study treatment defined as duration from date of first exposure to treatment to the first occurrence of ordinal scale equals "not hospitalized, no limitations of activities"	Date of first exposure to treatment to the first occurrence of ordinal scale equals "not hospitalized, no limitations of activities"
Change From Baseline in National Early Warning Score 2 (NEWS2) to Day 3, 7 and 14	NEWS2 is an assessment based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness) developed by the Royal College of Physicians (https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2). Respiratory rate (bpm) scores 0-3; Sp02 (on room air or suppl) scores 0-3; SpO2 (hypercapnic resp failure) scores 0-3; room air or supplemental O2 scores 0 (room) or 2 (suppl); temperature - scores 0-3; systolic BP scores 0-3; pulse (bpm) scores 0-3; consciousness - alert (score 0) vs. new onset confusion (score 3). The total possible score ranges from 0 to 20. The higher the score the greater the clinical risk. Higher scores indicate the need for escalation, medical review and possible clinical intervention and more intensive monitoring. Change shown is positive or negative from baseline, with a negative number indicating improvement (i.e., a decrease in total score).	Baseline to Day 3, 7 and 14
Mean Change in Percent Oxygen Saturation From Baseline to Days 3, 7 and 14	Mean change in percent oxygen saturation from baseline to Days 3, 7 and 14 for patients with paired values	Mean change in percent oxygen saturation from baseline to Days 3, 7 and 14
Change From Baseline in the Patient's Health Status on a 7-category Ordinal Scale on Days 3, 7 and 14	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. Lower scores mean a worse outcome.	Assessments performed Day 0 (first treatment is Visit 2, day 0), Visit 3 (3+/- 1 day after first treatment) Visit 4 (second treatment, 7+/- 1 day from V2, day7) and end of treatment (7+/- 1 day from V4, day 14)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Size of Lesion Area by Chest Radiograph or CT	Change in size of lesion area by chest radiograph or CT - exploratory endpoint	Day 14
Change From Baseline in Serum Cytokine and Chemokine Levels	Change from baseline in serum cytokine and chemokine levels at day 3, day 7 and day 14	Days 3, 7, and 14
Change From Baseline in CCR5 Receptor Occupancy Levels for Tregs and Macrophages	Change from baseline in CCR5 receptor occupancy levels for Tregs and macrophages at day3, day 7 and day 14	Days 3, 7, and 14
Change From Baseline in CD3+, CD4+ and CD8+ T Cell Count	Change from baseline in CD3+, CD4+ and CD8+ T cell count at day 3, day 7 and day 14	Days 3, 7, and 14

Collaborators and Investigators

• Sponsor: CytoDyn, Inc.
• Investigators: Principal Investigator: Angela Ritter, MD, Center for Advanced Research and Education

Publications and helpful links

Helpful Links

• NEWS2 Score

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Actual): July 21, 2020
• Study Completion (Actual): September 20, 2021

Study Registration Dates

• First Submitted: March 31, 2020
• First Submitted That Met QC Criteria: April 9, 2020
• First Posted (Actual): April 13, 2020

Study Record Updates

• Last Update Posted (Estimate): January 4, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2022
• Last Verified: December 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: CD10_COVID-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No