A not so brief reminder of what the DSMB does and why the actions of the DSMB for Cytodny CD 12 are a strong indication of the excellent results forthcoming.
The DSMB (Data Safety Monitoring Board) is an independent board with two primary responsibilities.
1) periodically review and evaluate the accumulated study data for participant safety, study conduct and progress, and, when appropriate, efficacy.
2) make recommendations to NIDCR concerning the continuation, modification, or termination of the trial.
So the DSMB first makes certain that patients in trials are safe.
Next the DSMB acts to make certain that trials which will be prove fruitless are terminated once likely failure is recognized or modify them sufficiently (larger trial size, less rigorous endpoints) so that they are successful.
Trials that are proceeding well with an expectation of meeting criteria for success, according to initial trial design are allowed to continue according to that initial trial design
So what has the DSMB done in Cytodyn CD12? Was the trial modified?
In fact the trial was modified, sort of.
Was the primary endpoint switched from mortality to something easier, say time to recovery (see Gilead's Remdesivir, Humanigen's lenzilumab)
No it was not.
Was the trial expanded to add more patients (see 56% increase in Humanigen's lenzilumab because the evidence supporting decreased time to clinical improvement was too small without adding more patients)
What trials changes did the Cytodyn DSMB want and why?
The DSMB reviewed CD12 after 100 patients, finding the trial was safe and could proceed without modification.
The DSMB reviewed CD12 after 50% enrollment (195 patients) and said the study could proceed without modification. No extra patients, no easier endpoint (LESS CLINICALLY MEANINGFUL, like the OTHER guys).
What did the DSMB suggest?
Another evaluation at review at 75%/293 enrollment.
Why would that happen?
Some would have us believe that leronlimab would suddenly become unsafe after its administration to more than 330 Covid patients (54+ EIND, 84 CD10, 195 CD12 50% enrollment) and many hundreds of HIV patients (I've lost track, but many)
What is the reason for this additional analysis?
The only logical reason is that the clinical results from the administration of Leronlimab to severe and critical Covid patients were so strong, even at 50% enrollment, that Leronlimab very nearly demonstrated overwhelming efficacy sufficient to stop the trial..
With an additional 50% more patients, the expectation was that the Leronlimab would meet the threshold to stop the trial and proceed to the FDA for authorization, EUA or approval, to allow administration to all severe and critical Covid patients.
Why did this not happen?
Simply that the pace of enrollment in CD12 accelerated so rapidly that the full 390 patients were enrolled before 28 days had elapsed for an additional DSMB assessment, and Cytodyn deemed it more appropriate and effective to analyze the data from the fully enrolled trial.
So where are we now?
Enrollment of 394 patients (more than planned, but Drs. Pourhassan and Kelly were not going to turn down patients in need) was complete December 16. The 28 day trial period will be complete January 13 (Wednesday) with data verification, locking and analysis completed shortly thereafter.
The proof is in the pudding.
We will know very soon whether
the remarkable improvements in the EIND patients
the reduction of clinical progression to severe and critical in CD10 trial
the complete lack of SAEs, the resumptions of FDA authorized EINDS
the authorization of Leronlimab to any severe or critical patients meeting the CD12 criteria at the 18 United States trials sites
mean that Leronlimab is the lifesaving therapeutic that administering physicians had been touting for months.
Perhaps the nameless faceless posters here exhorting us to save ourselves from financial ruin are correct and Leronlimab is complete and worthless junk, while the following physicians and research scientists, through their "Research" are in on the scam. (Sorry, it is a very long list)
Alina Lelic
Alina P.S. Pang
Amruta Pise
Arash Naeim
Benjamin N. Bimber
Bryant Yang
Byung S. Park
Christopher Bovinet
Christopher Sugai
David Goodman-Meza
David Sudduth, MD
Edgar B. Francisco
Eisa Mahyari
Enver Akalin
Eric Hall
Gabriela M. Webb
Hallison Rodrigues
Harish Seethamraju
Helen L. Wu
Jane A. O’Halloran
Jay Lelazari
Jenny Ahn
Jonah B Sacha
Kabir Mody
Kazem Kazempour
Kush Dhody
Lama Kdouh
Lishomwa C. Ndhlovu
Marlene Berro,
Matthew Plassmeyer
Michael J. Corley
Mohammed Elsharkawi
Monica Herrera
Nader Pourhassan
Nicholas Agresti
Oral Alpan
Otto O Yang
Philip A. Mudd
Phillip Amodeo
Raavi Gupta
Reejis Stephens
Scott Kelly
Seth Gross
Stephen Mosher
I doubt it.
The DSMB (Data Safety Monitoring Board) is an independent board with two primary responsibilities.
1) periodically review and evaluate the accumulated study data for participant safety, study conduct and progress, and, when appropriate, efficacy.
2) make recommendations to NIDCR concerning the continuation, modification, or termination of the trial.
So the DSMB first makes certain that patients in trials are safe.
Next the DSMB acts to make certain that trials which will be prove fruitless are terminated once likely failure is recognized or modify them sufficiently (larger trial size, less rigorous endpoints) so that they are successful.
Trials that are proceeding well with an expectation of meeting criteria for success, according to initial trial design are allowed to continue according to that initial trial design
So what has the DSMB done in Cytodyn CD12? Was the trial modified?
In fact the trial was modified, sort of.
Was the primary endpoint switched from mortality to something easier, say time to recovery (see Gilead's Remdesivir, Humanigen's lenzilumab)
No it was not.
Was the trial expanded to add more patients (see 56% increase in Humanigen's lenzilumab because the evidence supporting decreased time to clinical improvement was too small without adding more patients)
What trials changes did the Cytodyn DSMB want and why?
The DSMB reviewed CD12 after 100 patients, finding the trial was safe and could proceed without modification.
The DSMB reviewed CD12 after 50% enrollment (195 patients) and said the study could proceed without modification. No extra patients, no easier endpoint (LESS CLINICALLY MEANINGFUL, like the OTHER guys).
What did the DSMB suggest?
Another evaluation at review at 75%/293 enrollment.
Why would that happen?
Some would have us believe that leronlimab would suddenly become unsafe after its administration to more than 330 Covid patients (54+ EIND, 84 CD10, 195 CD12 50% enrollment) and many hundreds of HIV patients (I've lost track, but many)
What is the reason for this additional analysis?
The only logical reason is that the clinical results from the administration of Leronlimab to severe and critical Covid patients were so strong, even at 50% enrollment, that Leronlimab very nearly demonstrated overwhelming efficacy sufficient to stop the trial..
With an additional 50% more patients, the expectation was that the Leronlimab would meet the threshold to stop the trial and proceed to the FDA for authorization, EUA or approval, to allow administration to all severe and critical Covid patients.
Why did this not happen?
Simply that the pace of enrollment in CD12 accelerated so rapidly that the full 390 patients were enrolled before 28 days had elapsed for an additional DSMB assessment, and Cytodyn deemed it more appropriate and effective to analyze the data from the fully enrolled trial.
So where are we now?
Enrollment of 394 patients (more than planned, but Drs. Pourhassan and Kelly were not going to turn down patients in need) was complete December 16. The 28 day trial period will be complete January 13 (Wednesday) with data verification, locking and analysis completed shortly thereafter.
The proof is in the pudding.
We will know very soon whether
the remarkable improvements in the EIND patients
the reduction of clinical progression to severe and critical in CD10 trial
the complete lack of SAEs, the resumptions of FDA authorized EINDS
the authorization of Leronlimab to any severe or critical patients meeting the CD12 criteria at the 18 United States trials sites
mean that Leronlimab is the lifesaving therapeutic that administering physicians had been touting for months.
Perhaps the nameless faceless posters here exhorting us to save ourselves from financial ruin are correct and Leronlimab is complete and worthless junk, while the following physicians and research scientists, through their "Research" are in on the scam. (Sorry, it is a very long list)
Alina Lelic
Alina P.S. Pang
Amruta Pise
Arash Naeim
Benjamin N. Bimber
Bryant Yang
Byung S. Park
Christopher Bovinet
Christopher Sugai
David Goodman-Meza
David Sudduth, MD
Edgar B. Francisco
Eisa Mahyari
Enver Akalin
Eric Hall
Gabriela M. Webb
Hallison Rodrigues
Harish Seethamraju
Helen L. Wu
Jane A. O’Halloran
Jay Lelazari
Jenny Ahn
Jonah B Sacha
Kabir Mody
Kazem Kazempour
Kush Dhody
Lama Kdouh
Lishomwa C. Ndhlovu
Marlene Berro,
Matthew Plassmeyer
Michael J. Corley
Mohammed Elsharkawi
Monica Herrera
Nader Pourhassan
Nicholas Agresti
Oral Alpan
Otto O Yang
Philip A. Mudd
Phillip Amodeo
Raavi Gupta
Reejis Stephens
Scott Kelly
Seth Gross
Stephen Mosher
I doubt it.
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