Alyosha, A belated answer (have been a busy day
Post# of 147661
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Posted On: 02/09/2021 1:10:39 PM
Alyosha,
A belated answer (have been a busy day).
Their trial was similar to ours, there were some exclusion details that changed, and their cohort was smaller than our CD-12 (frankly, I don't think their power was well defined or they were expecting superb results).
However, the definition of Critical and Severe is the key: for example, in the Kevzara trial:
In the RLFTF trial they have:
[u]Conditions:[/u] Critical COVID-19 With Respiratory Failure
Acute Respiratory Distress Syndrome (ARDS)
Corona Virus Infection
Acute Lung Injury
And excluded:
Pregnancy (pregnant women may apply for open label treatment under compassionate care IND
Age <18 years
Mechanical ventilation for more than 7 days in primary cohort. Mechanical ventilation>21 days in the exploratory cohort
Mean Arterial Pressure < 65 mm Hg with use of pressor per ICU protocol
Irreversible condition (other than COVID-19) with projected fatal course
ECMO
Current or recent (within 30 d) enrollment in another investigational trial of anti-IL6 drug;
Active diagnosis of Acquired immune deficiency syndrome;
Transplant patients currently immunosuppressed;
Chemotherapy-induced neutropenia (granulocyte count <1000/mm3);
Cardiogenic shock; congestive heart failure - NYHA Class 3 or 4;
Recent myocardial infarction - within last 6 months and troponin > 0.5
Anuria (urine output < 50 ml/d) or other signs of multi-organ failure
Severe liver disease with portal hypertension;
Recent stroke or head trauma within last 12 months
Increased intracranial pressure, or other serious neurologic disorder;
Liquid Diarrhea more than 3x/day; defined as more than 3 non-bloody watery stools within a 24-hour period, requiring additional fluid and electrolyte supplementation
So, they were some "severe" for another definition in their trials. Our exclusion criteria is less demanding:
Exclusion Criteria:
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.
Not a candidate for dialysis or continuation of care (or full medical support) in setting of resource limitations.
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.
Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible.
Inability to provide informed consent or to comply with test requirements
Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment
Pregnancy or breast feeding
Subject participating in another study with for an investigational treatment for COVID-19.
It is impossible to ascertain what the split is between S/C in both trials but the fact that theirs had app. 32% (total) and ours 22% death-rate is very encouraging.
A belated answer (have been a busy day).
Their trial was similar to ours, there were some exclusion details that changed, and their cohort was smaller than our CD-12 (frankly, I don't think their power was well defined or they were expecting superb results).
However, the definition of Critical and Severe is the key: for example, in the Kevzara trial:
Quote:
Patients were classified as "severe" if they required oxygen supplementation without mechanical or high-flow oxygenation; or "critical" if they required mechanical ventilation or high-flow oxygenation or required treatment in an intensive care unit.
In the RLFTF trial they have:
[u]Conditions:[/u] Critical COVID-19 With Respiratory Failure
Acute Respiratory Distress Syndrome (ARDS)
Corona Virus Infection
Acute Lung Injury
And excluded:
Pregnancy (pregnant women may apply for open label treatment under compassionate care IND
Age <18 years
Mechanical ventilation for more than 7 days in primary cohort. Mechanical ventilation>21 days in the exploratory cohort
Mean Arterial Pressure < 65 mm Hg with use of pressor per ICU protocol
Irreversible condition (other than COVID-19) with projected fatal course
ECMO
Current or recent (within 30 d) enrollment in another investigational trial of anti-IL6 drug;
Active diagnosis of Acquired immune deficiency syndrome;
Transplant patients currently immunosuppressed;
Chemotherapy-induced neutropenia (granulocyte count <1000/mm3);
Cardiogenic shock; congestive heart failure - NYHA Class 3 or 4;
Recent myocardial infarction - within last 6 months and troponin > 0.5
Anuria (urine output < 50 ml/d) or other signs of multi-organ failure
Severe liver disease with portal hypertension;
Recent stroke or head trauma within last 12 months
Increased intracranial pressure, or other serious neurologic disorder;
Liquid Diarrhea more than 3x/day; defined as more than 3 non-bloody watery stools within a 24-hour period, requiring additional fluid and electrolyte supplementation
So, they were some "severe" for another definition in their trials. Our exclusion criteria is less demanding:
Exclusion Criteria:
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.
Not a candidate for dialysis or continuation of care (or full medical support) in setting of resource limitations.
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.
Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible.
Inability to provide informed consent or to comply with test requirements
Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment
Pregnancy or breast feeding
Subject participating in another study with for an investigational treatment for COVID-19.
It is impossible to ascertain what the split is between S/C in both trials but the fact that theirs had app. 32% (total) and ours 22% death-rate is very encouraging.
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