Study to Evaluate the Efficacy and Safety of Leronlimab for Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19)

• ClinicalTrials.gov Identifier: NCT04347239
• Recruitment Status: Active, not recruiting
• First Posted: April 15, 2020
• Last Update Posted: January 14, 2022
• Sponsor: CytoDyn, Inc.
• Information provided by (Responsible Party): CytoDyn, Inc.

Tracking Information

• First Submitted Date: April 13, 2020
• First Posted Date: April 15, 2020
• Last Update Posted Date: January 14, 2022
• Actual Study Start Date: April 15, 2020
• Actual Primary Completion Date: October 24, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 14, 2020)

All-cause mortality at Day 28 [ Time Frame: Day 28 ]

Day 0 refers to the data of randomization/first treatment.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 14, 2020)

• All-cause mortality at Day 14 [ Time Frame: Day 14 ]
  Day 0 refers to the data of randomization/first treatment.
• Change in clinical status of subject at Day 14 (on a 7 point ordinal scale) [ Time Frame: Day 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.
• Change in clinical status of subject at Day 28 (on a 7 point ordinal scale) [ Time Frame: Day 28 ]
  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.
• Change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 14. [ Time Frame: Day 14 ]
  The SOFA score assessment will be based on PaO2/FiO2, platelets, Glasgow coma scale (GCS), bilirubin, Mean arterial pressure OR administration of vasoactive agents required, and Serum creatinine

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Efficacy and Safety of Leronlimab for Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19)
• Official Title: A Phase 2b/3, Randomized, Double Blind, Placebo Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety of Leronlimab for Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19)
• Brief Summary: The purpose of this study is to assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injection in subjects with severe or critical COVID-19 disease.

Detailed Description

This is a Phase 2b/3, two-arm, randomized, double blind, placebo controlled, adaptive design multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with severe or critical 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.

A single arm, non-randomized, open-label phase is added to the protocol after completion of enrollment in the Randomized Phase of the study.

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

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

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
• Estimated Enrollment (submitted: March 18, 2021): 394
• Original Estimated Enrollment (submitted: April 14, 2020): 390
• Estimated Study Completion Date: June 15, 2022
• Actual Primary Completion Date: October 24, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female adult ≥ 18 years of age at time of screening.

2. Subjects hospitalized with severe or critical illness caused by coronavirus 2019 infection as defined below:

   A. Severe Illness:

   - Diagnosed with COVID-19 by standard RT-PCR assay or equivalent testing within 5 days of screening

   AND

   Symptoms of severe systemic illness/infection with COVID-19:

   - At least 1 of the following: fever, cough, sore throat, malaise, headache, muscle pain, shortness of breath at rest or with exertion, confusion, or symptoms of severe lower respiratory symptoms including dyspnea at rest or respiratory distress

   AND

   Clinical signs indicative of severe systemic illness/infection with COVID-19, with at least 1 of the following:

   - RR ≥ 30, HR ≥ 125, SaO2 <93% on room air or requires > 2L oxygen by NC in order maintain SaO2 ≥93%, PaO2/FiO2 <300

   AND

   - None of the following: Respiratory failure (defined by endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, or clinical diagnosis of respiratory failure in setting of resource limitations), Septic shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg), Multiple organ dysfunction/failure

   B. Critical Illness:

   - Diagnosed with COVID-19 by standard RT-PCR assay or equivalent testing within 5 days of screening

   AND

   Evidence of critical illness, defined by at least 1 of the following:

   - Respiratory failure defined based on resource utilization requiring at least 1 of the following: Endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (in setting of resource limitation)

   OR

   - Shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg or requiring vasopressors)

   OR

   -Multiple organ dysfunction/failure

3. Subject, if intubated, positive endexpiratory pressure (PEEP) <15 cmH2O with PaO2/FiO2 >150 mmHg.
4. Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator
5. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
6. Understands and agrees to comply with planned study procedures.
7. Women of childbearing potential and their partner must agree to use at least one highly effective method of contraception (e.g., hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], intrauterine devices, bilateral tubal occlusion, or sexual abstinence) for the duration of the study.

Exclusion Criteria:

1. Subjects with do-not-resuscitate (DNR) and/or do-not-intubate (DNI) orders or expected to be made DNR/DNI in setting of resource limitations or family wishes.
2. Not a candidate for dialysis or continuation of care (or full medical support) in setting of resource limitations.
3. Subject on continuous vasopressors (at the dose of norepinephrine >20μg/min and/or vasopressin >0.04 units/kg/min) for >48 hours at time of screening.
4. Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible.
5. Inability to provide informed consent or to comply with test requirements
6. Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment
7. Pregnancy or breast feeding
8. Subject participating in another study with for an investigational treatment for COVID-19.

Note: Subject who were prescribed (1) hydroxychloroquine or chloroquine with or without azithromycin, (2) Remdesivir, (3) convalescent plasma therapy, or (4) immunomodulatory treatments (including but not limited to sarilumab, clazakizumab, tocilizumab, and anakinra) for the off-label treatment of COVID-19 prior to study enrollment may be included and may continue to receive these agents as part of standard-of-care.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (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: NCT04347239
• Other Study ID Numbers: CD12_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

• Current Responsible Party: CytoDyn, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: CytoDyn, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: CytoDyn, Inc.
• Verification Date: January 2022