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

Coronavirus Disease 2019 Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04343651
• Other study ID #: CD10_COVID-19
• Status: Completed
• Phase: Phase 2
• Start date: April 1, 2020
• Est. completion date: September 20, 2021

Study information

• Verified date: December 2022
• Source: CytoDyn, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: September 20, 2021
• Est. primary completion date: July 21, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronavirus Disease 2019
• Coronavirus Infections
• COVID-19

Intervention

Drug:
• Placebo
Placebo
• Leronlimab (700mg)
Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Novant Health	Charlotte	North Carolina
United States	Ohio Health	Columbus	Ohio
United States	Center for Advanced Research & Education (CARE)	Gainesville	Georgia
United States	University of California, Los Angeles	Los Angeles	California
United States	Atlantic Health System Hospital	Morristown	New Jersey
United States	Yale	New Haven	Connecticut
United States	Palmtree Clinical Research, Inc.	Palm Springs	California
United States	Oregon Health and Science University	Portland	Oregon
United States	Eisenhower Health	Rancho Mirage	California
United States	White Plains Hospital	White Plains	New York

Sponsors (1)

Lead Sponsor	Collaborator
CytoDyn, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Primary	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	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).
Secondary	Incidence of Hospitalization	Number of patients requiring hospitalization	From visit 2 (day 0) through day 14 (in days)
Secondary	Duration (Days) of Hospitalization	Duration of hospitalization in days	Total duration of hospitalization between visit 2 (day 0) in days and end of treatment
Secondary	Incidence of Mechanical Ventilation	Incidence of mechanical ventilation supply	Total duration of mechanical ventilation since visit 2 (day 0) (days)
Secondary	Duration of Mechanical Ventilation Supply	Duration (days) of mechanical ventilation supply	Duration of mechanical ventilation since visit 2 (day 0) (days
Secondary	Incidence of Oxygen Use	Incidence of oxygen use over course of treatment	Use of oxygen since visit 2 (day 0) to end of treatment
Secondary	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)
Secondary	Mortality at Day 14	Incidence of mortality at day 14	Mortality at EOT (day 14)
Secondary	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"
Secondary	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
Secondary	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
Secondary	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)

External Links

•   NEWS2 Score