2016 Progress Report

Progress report on the L-serine HSAN1 Trial

by Florian Eichler, M.D.  (with Kailey Joan Walsh)

There were 18 subjects enrolled in this two-year, double-blind, placebo-controlled trial studying the efficacy of L-serine in patients with HSAN1. The study was initially randomized to placebo versus study drug, and both the participants and the investigators were blinded as to who was on placebo and who was on the study drug. At week 48 all participants were switched over to L-serine, regardless of their randomization from the previous year.

At the last DSMB (Data and Safety Monitoring Board) meeting (May 18, 2015) it was recommended that an open-label extension be added to the protocol. This would allow the continued collection of outcomes data on the first 16 subjects from the time they complete the original study to the time that the last two subjects complete the study in February 2016. Upon the board’s suggestion and after further investigation, it was decided that an extension of one year would be added to the protocol. After the original 2-year period, subjects would be given the option of being re-consented for the open label extension. All consented subjects would then be treated with L-serine (400 mg/kg/d) for an additional year. An amendment which included the updated protocol, protocol summary, and consent form was submitted and accepted by the IRB (Institutional Review Board) (7/24/2015). Due to budgetary restrictions it was decided that there would only be one additional visit added to the study via the open label extension rather than the two that were originally planned for.

Of the 18 subjects enrolled, 16 have completed their 96 week visit. We are in the process of scheduling subjects for their upcoming continuation visits. At this point the investigators are still blinded. They will remain blinded until the next DSMB meeting. The meeting, which will potentially be held in June, will be scheduled once we’ve received all of the results. We’re currently awaiting results from the deoxysphingolipid analysis which will be sent to us shortly from Zurich (Switzerland).

As of 3/22/16 there has been one serious adverse event (AE) reported. There have been 46 adverse events reported since randomization. Forty-five (45) AEs are not related to the study drug. One (1) AE is unlikely to be related to the study drug. Zero (0) AEs are possibly, probably, or definitely related to the study drug. 1 of the 46 AEs has been a SAE (Significant Adverse Event). Subject 701- 007 developed esophageal cancer which was unrelated to the study drug. Dr. Eichler regularly reviews the AEs to ensure subject safety.

As we prep for the final meeting we are ensuring data accuracy. We recently had an internal audit to ensure data integrity, and protocol compliance. We also had a FDA site visit on May 10th. We reviewed the progress of the study, and plans for the coming year. Looking forward we are planning to publically release the results at one of the top neurological conferences next fall.