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

• ClinicalTrials.gov Identifier: NCT04343651
• Recruitment Status: Active, not recruiting
• First Posted: April 13, 2020
• Last Update Posted: August 20, 2020
• Sponsor: CytoDyn, Inc.
• Information provided by (Responsible Party): CytoDyn, Inc.

Tracking Information

• First Submitted Date: March 31, 2020
• First Posted Date: April 13, 2020
• Last Update Posted Date: August 20, 2020
• Actual Study Start Date: April 1, 2020
• Actual Primary Completion Date: July 21, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 9, 2020)

Clinical Improvement as assessed by change in total symptom score (for fever, myalgia, dyspnea and cough) [ Time Frame: Day 14 ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 9, 2020)

• Time to clinical resolution (TTCR) [ Time Frame: Day 14 ]
• Change from baseline in National Early Warning Score 2 (NEWS2) [ Time Frame: Days 3, 7, and 14 ]
  This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). Higher scores mean a worse outcome.
• Change from baseline in pulse oxygen saturation (SpO2) [ Time Frame: Days 3, 7, and 14 ]
• Change from baseline in the patient's health status on a 7-category ordinal scale [ Time Frame: 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.
• Incidence of hospitalization [ Time Frame: Day 14 ]
• Duration (days) of hospitalization [ Time Frame: Day 14 ]
• Incidence of mechanical ventilation supply [ Time Frame: Day 14 ]
• Duration (days) of mechanical ventilation supply [ Time Frame: Day 14 ]
• Incidence of oxygen use [ Time Frame: Day 14 ]
• Duration (days) of oxygen use [ Time Frame: Day 14 ]
• Mortality rate [ Time Frame: Day 14 ]
• Time to return to normal activity [ Time Frame: Day 14 ]

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: April 9, 2020)

• Change in size of lesion area by chest radiograph or CT [ Time Frame: Day 14 ]
• Change from baseline in serum cytokine and chemokine levels [ Time Frame: Days 3, 7, and 14 ]
• Change from baseline in CCR5 receptor occupancy levels for Tregs and macrophages [ Time Frame: Days 3, 7, and 14 ]
• Change from baseline in CD3+, CD4+ and CD8+ T cell count [ Time Frame: Days 3, 7, and 14 ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Coronavirus Disease 2019

Intervention

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

Study Arms

• Placebo Comparator: Placebo
  Intervention: Drug: Placebos
• Experimental: 700mg Leronlimab
  Intervention: Drug: Leronlimab (700mg)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 10, 2020): 86
• Original Estimated Enrollment (submitted: April 9, 2020): 75
• Estimated Study Completion Date: August 31, 2020
• Actual Primary Completion Date: July 21, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04343651
• Other Study ID Numbers: CD10_COVID-19
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: CytoDyn, Inc.
• Study Sponsor: CytoDyn, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: CytoDyn, Inc.
• Verification Date: August 2020