NorthWest Biotherapeutics Inc (NWBO)

[Lykiri]

That’s a lot of substantial amendments made in the very short window of April 2015 to August 2015.

Sentiment,

IMO, it is more important that there wasn't a submission of a substantial amendment after the change in status of the DCVax-L trial. (Aug. 2015: new screening of patient candidates for the trial has been temporarily suspended. PR. https://nwbio.com/nw-bio-confirms-phase-iii-trial-of-dcvax-l-for-gbm-brain-cancer-is-ongoing/ )

After an "interruption" not provided in the protocol by the sponsor, you would have expected at least one submission of a substantial amendment to the study protocol. And i assume that there would have been a suspension of the favourable opinion by the REC. (On Aug.12, 2015 NWBO obtained a favourable opinion by the REC.)

When a trial is temporarily halted, the competent authorities (MHRA in the UK) and ethics committees of all member states concerned must be informed within 15 days of the halt. This notification should be in the form of a substantial amendment. Please refer to the MHRA web page for notification details and requirements for recommencing a trial.
http://www.ct-toolkit.ac.uk/routemap/temporary-halt-or-early-termination/

And here is the definition of a "halt of recruitment due to a safety related issue":

10.8 Question: Would a halt of recruitment be considered as a temporary halt of a clinical trial or of an end of recruitment?

306. Answer: If the recruitment is stopped due to a potential change in the benefit-risk balance (e.g a safety related issue), this should be notified as a temporary halt of the clinical trial. The sponsor should notify the Member States concerned without undue delay but not later than 15 days, including reasons for such action and specify follow up (article 38 of the Clinical Trials Regulation).
An additional change of benefit-risk notification or an urgent safety measure may need to be submitted. The sponsor should apply for a substantial modification before re-starting the clinical trial (article 38 of the Clinical Trials Regulation)

10.4 Question: How is "temporary halt of a clinical trial" defined.

297. Answer: Article 2 (28) of the Clinical Trials Regulation defines the "temporary halt of a clinical trial" as an "interruption not provided in the protocol of the conduct of a clinical trial by the sponsor with the intention of sponsor to resume it." This could also be part of an urgent safety measure (article 54 of the Clinical Trials Regulation).

https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-10/regulation5362014_qa_en.pdf

IMO, you can conclude that the hold on recruitment was not a safety related issue. If it was a safety related issue, the terminology used by the RA would be correct = temporary halt of the trial.
This is what Northwest Biotherapeutics told us:

Some blogs and social media comments have noted that the EudraCT trials database in Europe states that there is a “Temporary Halt” of the trial in Germany. In actuality, the trial status in Germany is that the trial is ongoing as noted above, and the Company has only undertaken a temporary suspension of new screening.

The Company has sought to have the EudraCT listing corrected, but the database includes only certain pre-specified categories and there is no category that corresponds to a temporary suspension of new screening only, while a trial is ongoing.

I am more and more of the opinion that the "temporary hold on recruitment" was part of the protocol, the one that has obtained conditional approval from the German regulatory authority (the Paul Ehrlich Institute, or PEI - Aug. 2014)

The Company has obtained approval from the US FDA and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) and conditional approval from the German regulatory authority (the Paul Ehrlich Institute, or PEI). The Company is now working toward the final approval from the PEI.
https://nwbio.com/nw-bio-obtains-approvals-for-enhancements-of-phase-iii-trial-of-dcvax-l-for-gbm-brain-cancer/

And remember Woodford-Sept. 2015.:

Our US biotech holdings were also hit hard. The month’s largest detractor was Northwest Biotherapeutics, after rumours that the clinical trial of its DCVax-L oncology treatment had been suspended. The company has confirmed that the suspension related simply to the recruitment of new patients and was a temporary measure while regulatory information was submitted, in line with clinical protocols.
The trial is continuing and we see nothing untoward in this development.

Alkermes and Prothena sold off heavily too – again, we have no fundamental grounds for concern and were able to take advantage of the share price weakness.

https://www.willisowen.co.uk/insights/article_print?ID=103