In the open label extension study that will follow the Phase 3 trial, all participants will be followed to evaluate the long term tolerability and safety of trofinetide. No time limit has been given for the extension study. I have seen trials with extension study periods of between 6 months and 2 years, but often the extension period runs right through until the the drug is licensed for sale.
One potential benefit of a properly designed and conducted open label extension study is that it can provide more rigorous information on the long term safety and tolerability of the investigative drug.As well as helping to ensure that nothing has been missed, the longer span of patient data can also be helpful when seeking regulatory approval.
From the patient and carer perspective, a potential benefit is that patients who experience positive improvements during the trial don’t have to face the disappointment of regression when the drug is stopped. The amazing Mel Lancaster provided some insight into this in her
Trail to a Texas Trial blog.
Facebook has reminded me on an almost daily basis since November of Katelin’s participation in the Adult trial (Phase II of NNZ-2566, now Trofinetide) I have been able to skip down memory lane in a way that wouldn’t have been possible without the technology in place today. I’ve rewatched and reread our journey, day by day. It really seems impossible to believe it’s been four years already and that soon we’ll be moving on to Phase III. I’ve watched her draw her circle, I’ve lost count how many times. I watched her pour paint, I remembered it, but had forgotten that I caught it on tape. lol, tape. I’m dating myself. And, I relived again her regression afterwards. I’m glad she doesn’t have Facebook (YET) as I imagine it would be terribly difficult for her to relive it. I had the advantage, as I was ready, but it was still awfully sad.Another potential benefit is that participating trial patients (and their carers) know that, even if they are one of the unlucky number to be allocated to the placebo group during the trial, there is the possibility of access to the investigative drug after 3 months.
From the drug sponsor perspective, more data provides an even better profile of the drug’s safety and tolerability which can be helpful when seeking regulatory approval. In addition, faster patient recruitment is likely, as patients know that, even if they are placed on placebo during the trial, there is the possibility of access to the real drug during the extension period. (Not that I think patient recruitment will be a problem, even without the extension study). Finally, extension study periods can be beneficial for drug sponsors from a marketing perspective, although this should never be the reason for a drug sponsor to include an extension study.
One potential downside of open label extension studies
is that any participants within the active drug group during the trial who experienced tolerability issues would be unlikely to take part in the extension study. The absence of this group has the potential to introduce bias and increase the apparent tolerability of the new drug. Therefore, it is important that analysis strategies be developed and implemented to provide unbiased estimates of safety and tolerability.https://trailtoatexastrial.wordpress.com/2017/12/27/heres-to-a-new-year-and-a-new-hope/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200598/https://www.clinicalleader.com/doc/use-extension-studies-to-enhance-phase-data-0001
(20min delay)