Replies to post #168944 on Anavex Life Sciences Corp (AVXL)

[dia76ca]

Working with rett.org they could enroll and dose all 15 little girls in a month IMO. There could be signs of improvement by Christmas. Wouldn't that be great!

[GrassyKnoll]

It is probable that recruitment is done. Do we have to wait for the pre-does saying observation, or is that already done to?

[Steady_T]

A careful reading of the PR suggests that the 15 person trial is to do dose titration and determine what doses are appropriate for the large placebo controlled follow on trial. The size of which was not disclosed. They rolled that into the Phase 2 trial but to me it looks like a hybrid between a phase 1 and phase 2, only using Rett girls instead of the healthy young adults used in the AU Phase 1 trial.

I can see why the FDA might take a long look at this trial protocol.

The previous phase 1 used healthy young adults and established safety and MTD. Rett girls are pediatric subjects in many cases so there are a lot of questions raised by that factor. Rett girls already have a lot of issues that make the phase 1 results less applicable because of the lack of equivalence in subjects. That placed the FDA in a difficult position. The trial needs to determine the dosages that young Rett girls can tolerate and look for drug reactions due to the disturbed body chemistry of the Rett girls. There is no readily available equivalent population to do these studies on, so the FDA approved a small population, dose titration study using Rett diagnosed girls. That limits the risk to a small population before proceeding on to a larger trial population.

I would imagine there was a LOT of discussion within the FDA about how to do that and the safety and ethical implications involved.

I vaguely remember the number 60 being mentioned in times past. Whether that is still the case or not I do not know.

[Doc328]

I would estimate the following timeline:
1. I assume they already wrote a protocol, if not add 2-4 weeks.

2. Site selection will be easy as there are probably only 12-20 possible sites for a phase 1 for Rett as the disease is too rare to go outside of one of the Rett Centers. For 15 patients they may only need 3 sites (range 1-5). They probably have the few sites already picked and the site selection (pre-study) visit can likely be skipped, replaced by a phone conference to review the final protocol. Each site will then need to turn in an application to an IRB. Theoretically, this process could be as fast as 2 weeks. However, academic centers usually insist that their own IRB be used instead of an independent IRB and that can add another month (or more). Then they can do the study initiation visits. Depending on whether all sites are synchronized with IRB approvals, this could be done at a common investigator meeting. If they just have one site that can use a central IRB, then this whole step could be 2 weeks but with several sites it will likely be 2 months to get all sites up.

3. I assume that all selected sites have "pre-screened" patients to identify those in general good health who have parents willing to comply with the protocols. The coordinator will need to inform the parents when they are ready to enroll. I start pre-screening for studies a month or so before they start so the coordinator can contact them as soon as we are cleared. So this could be as quick as a few days. Because PK/PD data is being selected and a couple blood draws may be needed day 1 and again at 24 and 48 hours, sites may not be able to enroll as rapidly as some believe. I think it will take a minimum of 2 months to get the 15 patients assuming 3 sites and would not be surprised if it took 4 months. The Neuren pediatric study took 5-6 months to enroll 82 patients at 12 sites. If they are up against Christmas they may wait to start until the New Year.

4. Add 7 weeks for the last patient to be out and are at 5-8 months for the first study so I agree with your estimate or summer 2019

5. They will need to then decide on details of the second study protocol based on results (minimum couple months analysis and protocol dessign) and 12 months minimum will be needed for site recruitment/IRB, patient recruitment, study and analysis. So best case would be 3Q2020 but early 2021 more likely.