Replies to post #63947 on NorthWest Biotherapeutics Inc (NWBO)

[Rkmatters]

They added the crossover to help with enrollment. Interest in the trial was not the issue, instead getting patients to remain in the trial was. There are many post about this topic last year. As for the patient count, it is clear in subsequent SEC filings and PRs. The Company confirmed 33 patients confirmed in January 2011, giving a sense the trial was further along than it was.

NWBO, January 2011 – "To date, this trial has been conducted at 13 clinical sites across the U.S., with 33 patients already having been enrolled. "

In May 2011, they elaborate on the 33 patients, making it clear that not all patients were in the blinded portion of the study.

NWBO May 2011 Enrollment PR: "To date, 33 patients have already been enrolled in this ongoing 240-patient GBM brain cancer trial and its information arm an have been proceeding through the treatment regimen and follow-up.”

There were likely probably a good 17 that were in the "open" pre-placebo days "information arm", which is not the same thing as a compassionate use arm. That was determined by Dr. Gruber's comments. Hope this helps.

Rough timeline:
-- NCT opened in 2006 continues to today
-- Open randomized study began in 2007 without placebo
-- Four clinical sites, screened roughly 50 patients; Recruitment in control arm poor due to patients knowing classification, control patients dropped out per 2007 10K (repeated 10K verbiage subsequent years: 2008, 2009, etc.)
-- recruitment stopped in 2007/2008 and company developed a placebo; obtained renewals of institutional review board or IRB approvals and other necessary steps; reinitiated approvals at all clinical sites, approvals granted.
-- Kathy Montag surgery in December 2007; joined DCVax Ph II Double-blinded study but didn't get vaccine until April/May 2008
-- Double-blinded study PR to start in May 2008
-- Dr. Gruber, Principal Investigator for NYU and Overlook quoted stating in the Star Ledger in June 2008 “Overlook is running the trial in conjunction with NYU and so far has enrolled 20 patients." - His quote had to have included both “open - pre-placebo patients” and “double-blinded patients”. See next bullet
-- June 2008 10Q, released on August 19, 2008, company quoted as "to date only 6 patients have enrolled in the clinical trial, which is designed to include 240-patients. Given our lack of funding, it is unclear how quickly we will be able to increase enrollment, if at all. unsure if they could enroll more, financial constraints."
-- Nurses blog in Sept 2008 story on Kathy Montag, Overlook Nurse, as that time Overlook reported to have enrolled 3 patients in Double Blinded Phase III since it began (a drop of 17 patient count from Dr. Gruber's June statement).
-- Sept 2008 10Q released on November 19, 2008, again company quoted "to date only 11 patients have enrolled in the clinical trial, which is designed to include 240-patients. Given our lack of funding, it is unclear how quickly we will be able to increase enrollment, if at all."
-- January 2009, 13 sites prepared and ready to enroll (only 4 were recruiting though; and they were laying off employees, down from 7 to 4 so doubtful that they enrolled a single patient during this time; they did try to raise money and kept it open for a while)
-- NCT site records recruiting as stopped mid-year.
-- January 2011 PR [mine]:
To date, this trial has been conducted at 13 clinical sites across the U.S., with 33 patients already having been enrolled.
These patients have continued to be treated with the DCVax® regimen and follow-up during the last two years. The only aspect of the trial that stopped for a period of time was the enrollment of additional new patients beyond the 33 patients who were already enrolled and receiving ongoing treatment.
[only 4 were recruiting per 2009 10k statements; when they speak of trial, they mean NCT # 2006-forward];
— May 2011 PR, they elaborate more on the 33 patients (from both the 2007-2008 (open label) and 2008-2009 (double-blinded) period), and it is clear they are mix of “double blinded main arm” and “information arm”, which is not the same thing as CUA:
“To date 33 patients have already been enrolled in this ongoing 240-patient GBM brain cancer trial and its information arm, and have been proceeding through the treatment regimen and follow-up”.
[240-patient GBM brain cancer trial, meaning the entire NCT #, as it changed from 141-patients to 240-patients, as they don’t just state double-blinded.]
— When the study resumed in August 2011, the compassionate use arm existed (CUA).
— Revamped as Phase III, in 2012, they stopped the CUA, added a psPD arm and all "failed screen" patients had to pass baseline 2 to enter psPD arm.

[sentiment_stocks]

There definitely were patients that remained in the trial after it's first attempt. This would have been the group that enrolled in the trial leading up to the hold. They are called the "vanguard" cohort. Those patients enrolled in the trial after the hold are called the "restart" cohort.

The following is per the April 2013 protocol.

Efficacy will also be reviewed at the two interim analyses plus one final
analysis. Overall cohort (i.e., all data from the beginning of the study,
followed by the “vanguard” cohort – i.e. those patients originally enrolled
prior to the hold and followed up to the current time, and a “restart cohort”,
i.e., those follow-up since the restart of the clinical trial (i.e., since August
2011). Although the primary view is towards all patients enrolled (i.e. overall
cohort), a consistency of effect across subsets would be the primary intent
of these additional cuts.

I believe those "vanguard" patients numbered approximately 22 or so from an original number of 33. The remaining 11 were enrolled into the information arm.

They will count towards the "overall cohort".