Clinical trial NCT04347239: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Coronavirus Disease 2019
Keywords: COVID-19
Lead sponsor: CytoDyn, Inc.
Sponsor class: INDUSTRY
First posted: 2020-04-15
Enrollment: 394
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: All-cause mortality at Day 28
timeFrame: Day 28
Secondary outcomes:
measure: All-cause mortality at Day 14
timeFrame: Day 14
measure: Change in clinical status of subject at Day 14 (on a 7 point ordinal scale)
timeFrame: Day 14
measure: Change in clinical status of subject at Day 28 (on a 7 point ordinal scale)
timeFrame: Day 28
measure: Change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 14.
timeFrame: Day 14
Other outcomes:
Locations:
city: Alexander City
country: United States
facility: Advanced Cardiovascular, LLC
state: Alabama
city: Fullerton
country: United States
facility: St. Jude Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Tampa
country: United States
facility: James A. Haley Veterans' Hospital
state: Florida
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: Livingston
country: United States
facility: St. Barnabas
state: New Jersey
city: Morristown
country: United States
facility: Atlantic Health System Hospital
state: New Jersey
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Brooklyn
country: United States
facility: New York Community Hospital of Brooklyn
state: New York
city: Winston-Salem
country: United States
facility: Novant Health
state: North Carolina
city: Columbus
country: United States
facility: Ohio Health
state: Ohio
city: Corvallis
country: United States
facility: Good Samaritan Hospital Corvallis
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Sciences University
state: Oregon
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: University of Texas
state: Texas
Study officials:
References: