In an effort to complete the AGLU02704 study (Late-Onset Treatment Study, LOTS) as responsibly as possible, Genzyme has amended the study protocol to incorporate the use of an adaptive design. Genzyme utilized this method to help ensure a conclusive trial outcome in this small group of participants, and worked with regulatory agencies and study investigators to implement it. Under this adaptive design, an independent statistical center (ISC) and the Pompe Data Safety Monitoring Board (DSMB) examined study data to recommend a study end date that would ensure the most robust study outcome. Genzyme, study investigators, and study participants remain blinded to the treatment assignments and to the ISC data analyses.
The statistical analysis occurred in late December, 2006 and the ISC and DSMB recommended that each study participant should complete 18 months (78 weeks) of double blind treatment. Genzyme has accepted this recommendation to end the study in September of 2007, which will allow for the collection of sufficient data to discern a conclusive trial outcome with the greatest statistical confidence. Based on the current enrollment, the last study visit will be completed in September, 2007; however, some participants will begin to reach their 18 month visit as early as March of 2007.
Study investigators and participants have been notified of these changes to the trial design and the new timeframes. In order to complete the LOTS trial under the adaptive design, all study participants will need to remain in the LOTS trial for 18 months (6 months longer than the original protocol). Investigators discussed this possibility with study participants when the adaptive design was implemented. Genzyme is aware of the impact this change has on participants and the clinical team has been working to establish local infusion sites for the majority of participants.
Now that Myozyme® (alglucosidase alfa) is commercially available, there may not be another opportunity to collect data in a controlled way to adequately demonstrate safety and efficacy to the appropriate regulatory authorities in order to support the full patient population. Therefore, the completion of the study is of paramount importance for the Pompe community.
Furthermore, as a Post Marketing Commitment to the FDA, Genzyme has agreed to complete an open-label Extension Study (AGLU03206), where all participants will receive treatment with Myozyme, to follow the LOTS study. Study participants who successfully complete LOTS will be eligible to roll over into the AGLU03206 extension study as per the protocol’s inclusion/exclusion criteria. The minimum total duration of study participation in both LOTS and the open-label Extension Study combined is 24 months.
As with all clinical trials, when a study is completed, the final data collection, analysis, and presentation of the results can take several months. Data from the LOTS trial will be submitted to the appropriate regulatory agencies worldwide. Those authorities will determine if the safety and efficacy data can be used to update their respective prescribing labels as appropriate.
Genzyme would like to acknowledge and thank the patient community and study investigators for their ongoing commitment to successfully complete the LOTS trial and their continued support of obtaining this critically important information for the Pompe community.