Clinical trial NCT04343651: Study to Evaluate the Efficacy and Safety of Leronlimab for Mild to Moderate COVID-19
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronavirus Disease 2019
Keywords: COVID-19
Lead sponsor: CytoDyn, Inc.
Sponsor class: INDUSTRY
First posted: 2020-04-13
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Change From Baseline in Total Symptom Score
timeFrame: Clinical Improvement will be assessed at baseline and at EOT (day 14).
Secondary outcomes:
measure: Time to Clinical Resolution (TTCR)
timeFrame: Time (in days) from initiation of study treatment until resolution of clinical symptoms (fever, myalgia, dyspnea and cough).
measure: Incidence of Hospitalization
timeFrame: From visit 2 (day 0) through day 14 (in days)
measure: Duration (Days) of Hospitalization
timeFrame: Total duration of hospitalization between visit 2 (day 0) in days and end of treatment
measure: Incidence of Mechanical Ventilation
timeFrame: Total duration of mechanical ventilation since visit 2 (day 0) (days)
measure: Duration of Mechanical Ventilation Supply
timeFrame: Duration of mechanical ventilation since visit 2 (day 0) (days
measure: Incidence of Oxygen Use
timeFrame: Use of oxygen since visit 2 (day 0) to end of treatment
measure: Duration of Oxygen Use
timeFrame: Total duration of oxygen use since visit 2 (day 0) to EOT (day 14) (days)
measure: Mortality at Day 14
timeFrame: Mortality at EOT (day 14)
measure: Time to Return to Normal Activity
timeFrame: Date of first exposure to treatment to the first occurrence of ordinal scale equals "not hospitalized, no limitations of activities"
measure: Change From Baseline in National Early Warning Score 2 (NEWS2) to Day 3, 7 and 14
timeFrame: Baseline to Day 3, 7 and 14
measure: Mean Change in Percent Oxygen Saturation From Baseline to Days 3, 7 and 14
timeFrame: Mean change in percent oxygen saturation from baseline to Days 3, 7 and 14
measure: Change From Baseline in the Patient's Health Status on a 7-category Ordinal Scale on Days 3, 7 and 14
timeFrame: 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 outcomes:
measure: Change in Size of Lesion Area by Chest Radiograph or CT
timeFrame: Day 14
measure: Change From Baseline in Serum Cytokine and Chemokine Levels
timeFrame: Days 3, 7, and 14
measure: Change From Baseline in CCR5 Receptor Occupancy Levels for Tregs and Macrophages
timeFrame: Days 3, 7, and 14
measure: Change From Baseline in CD3+, CD4+ and CD8+ T Cell Count
timeFrame: Days 3, 7, and 14
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Palm Springs
country: United States
facility: Palmtree Clinical Research, Inc.
state: California
city: Rancho Mirage
country: United States
facility: Eisenhower Health
state: California
city: New Haven
country: United States
facility: Yale
state: Connecticut
city: Gainesville
country: United States
facility: Center for Advanced Research & Education (CARE)
state: Georgia
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Morristown
country: United States
facility: Atlantic Health System Hospital
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: White Plains
country: United States
facility: White Plains Hospital
state: New York
city: Charlotte
country: United States
facility: Novant Health
state: North Carolina
city: Columbus
country: United States
facility: Ohio Health
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
Study officials:
affiliation: Center for Advanced Research and Education
name: Angela Ritter, MD
role: PRINCIPAL_INVESTIGATOR
References: