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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Coronavirus Disease 2019

Intervention / Treatment
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* Drug: Placebo
* Drug: Leronlimab (700mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adult ≥ 18 years of age at time of enrollment. 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 Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal 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 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: Subjects showing signs of acute respiratory distress syndrome (ARDS) or respiratory failure necessitating mechanical ventilation at the time of screening; History of severe chronic respiratory disease and requirement for long-term oxygen therapy; Subjects showing signs of clinical jaundice at the time of screening; History of moderate and severe liver disease (Child-Pugh score >12); Subjects requiring Renal Replacement Therapy (RRT) at the time of screening; History of severe chronic kidney disease or requiring dialysis; 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. Patients with malignant tumor, or other serious systemic diseases; Patients who are participating in other clinical trials; 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 Inability to provide informed consent or to comply with test requirements

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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<br>* Placebo<br>|
| Experimental: 700mg Leronlimab<br>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)<br>* Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)<br>* Other names: PRO 140;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19