Following was posted by Science + Compliance on YMB
I manage clinical trials and have done so for a significant part of my career. We choose secondary endpoints that measure biomarkers that we know/should are/be affected by the efficacy of our drugs. We often use double-blind trials since they are seen as the most reliable type of study because they involve neither the participant nor the doctor knowing who has received what treatment. The aim of this is to minimize the placebo effect and minimize bias. Buried in the secondary endpoints are those lab tests conducted to measure the biomarkers that cause the pendulum to swing in a specific (favorable or definitive) direction.
With this said, Dr. Patterson’s expertise in RANTES, CCL5, CCR5, and the internal CytoDyn expertise CYDY I believe clearly knows based upon scientific judgement and the labs conducted @ Day 14 (See below) during the monitoring period to measure specific parameters who in the placebo and who in the Leronlimab group has passed.
The three sections below are the secondary endpoints in addition to the 28 Day all-cause mortality:
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
Drawing attention to the Glasgow coma scale these are VERY biased towards a patient NOT receiving Leronlimab:
Eye Opening Response
• Spontaneous--open with blinking at baseline 4 points
• To verbal stimuli, command, speech 3 points
• To pain only (not applied to face) 2 points
• No response 1 point
Verbal Response
• Oriented 5 points
• Confused conversation, but able to answer questions 4 points
• Inappropriate words 3 points
• Incomprehensible speech 2 points
• No response 1 point
Motor Response
• Obeys commands for movement 6 points
• Purposeful movement to painful stimulus 5 points
• Withdraws in response to pain 4 points
• Flexion in response to pain (decorticate posturing) 3 points
• Extension response in response to pain (decerebrate posturing) 2 points
• No response 1 point
And now drawing attention to the platelets and bilirubin lab tests, these results are directly linked to RANTES. One cytokine that is highly expressed in inflammatory states is CCL5 (RANTES). CCL5, which is abundant in human platelets, signals predominantly through CCR5, a 7-transmembrane G-protein–coupled receptor that mediates diverse signaling cascades. Further, in times of physiological stress, platelet count can transiently rise.
I believe that collection and analysis (statistical analysis as well) of lab data at Day-14 provided the needed evidence for CytoDyn to determine if the outcome of the s/c study would be successful. I believe CytoDyn has known which way the pendulum will swing based upon these secondary endpoints lab data as the results have come in. These tests are not specialty tests and should be conducted quickly and easily. Some companies batch lab samples and others test as they are collected. Not knowing how the sample testing process was performed could provide clues to perceived delays.
The aggressive posture CytoDyn has taken to further activities supportive of a favorable s/c study are confirmation in my humble opinion to the outcome already being known. There have also been MANY hints cryptically provided during the conference calls that some think are a waste of time. If I didn’t know any better, I think this approach may be by design.
I manage clinical trials and have done so for a significant part of my career. We choose secondary endpoints that measure biomarkers that we know/should are/be affected by the efficacy of our drugs. We often use double-blind trials since they are seen as the most reliable type of study because they involve neither the participant nor the doctor knowing who has received what treatment. The aim of this is to minimize the placebo effect and minimize bias. Buried in the secondary endpoints are those lab tests conducted to measure the biomarkers that cause the pendulum to swing in a specific (favorable or definitive) direction.
With this said, Dr. Patterson’s expertise in RANTES, CCL5, CCR5, and the internal CytoDyn expertise CYDY I believe clearly knows based upon scientific judgement and the labs conducted @ Day 14 (See below) during the monitoring period to measure specific parameters who in the placebo and who in the Leronlimab group has passed.
The three sections below are the secondary endpoints in addition to the 28 Day all-cause mortality:
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
Drawing attention to the Glasgow coma scale these are VERY biased towards a patient NOT receiving Leronlimab:
Eye Opening Response
• Spontaneous--open with blinking at baseline 4 points
• To verbal stimuli, command, speech 3 points
• To pain only (not applied to face) 2 points
• No response 1 point
Verbal Response
• Oriented 5 points
• Confused conversation, but able to answer questions 4 points
• Inappropriate words 3 points
• Incomprehensible speech 2 points
• No response 1 point
Motor Response
• Obeys commands for movement 6 points
• Purposeful movement to painful stimulus 5 points
• Withdraws in response to pain 4 points
• Flexion in response to pain (decorticate posturing) 3 points
• Extension response in response to pain (decerebrate posturing) 2 points
• No response 1 point
And now drawing attention to the platelets and bilirubin lab tests, these results are directly linked to RANTES. One cytokine that is highly expressed in inflammatory states is CCL5 (RANTES). CCL5, which is abundant in human platelets, signals predominantly through CCR5, a 7-transmembrane G-protein–coupled receptor that mediates diverse signaling cascades. Further, in times of physiological stress, platelet count can transiently rise.
I believe that collection and analysis (statistical analysis as well) of lab data at Day-14 provided the needed evidence for CytoDyn to determine if the outcome of the s/c study would be successful. I believe CytoDyn has known which way the pendulum will swing based upon these secondary endpoints lab data as the results have come in. These tests are not specialty tests and should be conducted quickly and easily. Some companies batch lab samples and others test as they are collected. Not knowing how the sample testing process was performed could provide clues to perceived delays.
The aggressive posture CytoDyn has taken to further activities supportive of a favorable s/c study are confirmation in my humble opinion to the outcome already being known. There have also been MANY hints cryptically provided during the conference calls that some think are a waste of time. If I didn’t know any better, I think this approach may be by design.
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