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

Coronavirus Disease 2019 Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04347239
• Other study ID #: CD12_COVID-19
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 15, 2020
• Est. completion date: June 15, 2022

Study information

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

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 394
• Est. completion date: June 15, 2022
• Est. primary completion date: October 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronavirus Disease 2019
• Coronavirus Infections
• COVID-19

Intervention

Drug:
• Placebos
Placebos
• 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	Advanced Cardiovascular, LLC	Alexander City	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	New York Community Hospital of Brooklyn	Brooklyn	New York
United States	Ohio Health	Columbus	Ohio
United States	Good Samaritan Hospital Corvallis	Corvallis	Oregon
United States	Baylor Scott & White Research Institute	Dallas	Texas
United States	St. Jude Medical Center	Fullerton	California
United States	Center for Advanced Research & Education (CARE)	Gainesville	Georgia
United States	Baylor College of Medicine	Houston	Texas
United States	University of Texas	Houston	Texas
United States	St. Barnabas	Livingston	New Jersey
United States	UCLA	Los Angeles	California
United States	Atlantic Health System Hospital	Morristown	New Jersey
United States	Oregon Health and Sciences University	Portland	Oregon
United States	James A. Haley Veterans' Hospital	Tampa	Florida
United States	Holy Name Medical Center	Teaneck	New Jersey
United States	Novant Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
CytoDyn, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality at Day 28	Day 0 refers to the data of randomization/first treatment.	Day 28
Secondary	All-cause mortality at Day 14	Day 0 refers to the data of randomization/first treatment.	Day 14
Secondary	Change in clinical status of subject at Day 14 (on a 7 point ordinal scale)	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.	Day 14
Secondary	Change in clinical status of subject at Day 28 (on a 7 point ordinal scale)	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.	Day 28
Secondary	Change from baseline in Sequential Organ Failure Assessment (SOFA) score at 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	Day 14