FDA did not issue any warning letters to Sponsors/Monitors/CROs, IRBs or Clinical Investigators last week or this week. From the archives, the Clinical Inspection Summary for Cotellic (cobimetinib fumarte) by Genentech shows that four of 132 sties participating in the pivotal study plus the sponsor were inspected. Site inspections ranged from three to four days, and the sponsor inspection lasted a week. One site was classified as voluntary action indicated and one site was classified as official action indicated.
Dr. Ascierto received a 483 for failing to follow the investigational plan, specifically:
- Three subjects were enrolled with ECG values for QTcF that exceeded protocol limits.
- FDA notes that the monitor had discovered the issue, and the sponsor had approved subjects remaining on the trial. FDA notes that at the time of the enrollment, the PI had determined that the QTcF values for two of the subjects were not clinically significant and the value for the third subject was a transcription error.
Dr. Ferraresi received a 483 for the following:
- Failing to promptly report adverse events to the sponsor.
- Three subject hospitalization were reported late to the sponsor.
- Failure to report unanticipated problems to the IRB.
- Serious adverse events (SAEs) and adverse drug reactions (ADRs) were not reported as required to the IRB.
- The IRB did not approve a written summary of a short form/verbal consent that was given to a subject
- Failure to follow the investigational plan
- Several study procedures, imaging and laboratory tests were missed or conducted out of window for all eleven subjects enrolled.
- Inadequate investigational product accountability records
- For six subjects, patient diaries do not match source records or the investigational product accountability logs.
- Two subjects were given the incorrect lot of investigational product
- FDA notes that Dr. Ferraresi's conduct of the the trial was "marginal"., and that some of the deviations noted placed subjects at undue risk. FDA notes that as part of the review process, a sensitivity analysis was performed on data collected from this site, for progression free survival as well as the Kaplan-Meier curve for the Intent to Treat population.