A Long-Term Extension Study of AT2101 (Afegostat Tartrate) in Type 1 Gaucher Patients

An Open-Label, Multicenter, Long-Term Extension Study To Assess The Safety, Efficacy, And Pharmacodynamics Of AT2101 In Adult Patients With Type 1 Gaucher Disease

This study evaluated the long-term safety and efficacy of afegostat tartrate in participants with Gaucher disease who were enrolled in a previous Phase 2 study of afegostat tartrate.

This was an open-label, long-term extension study of afegostat tartrate in participants with type 1 Gaucher disease who successfully completed Study GAU-CL-202 (NCT00446550). Participants could enter the study immediately upon completion of participation in the lead-in study GAU-CL-202, or at any later time point. Participants received 225 milligram (mg) afegostat tartrate, administered orally for 30 months, and remained in 1 of the 2 randomized treatment regimens of Study GAU-CL-202: afegostat tartrate once daily (QD) for 3 consecutive days, then no afegostat tartrate for 4 consecutive days (consecutive 3-days-on/4-days-off) or QD for 7 consecutive days, then no afegostat tartrate for 7 days (consecutive 7-days-on/7-days-off). Amendment 2 removed the 7-days-on/7-days-off regimen and added an alternative 3-days-on/4-days-off regimen: afegostat tartrate QD on Monday, Wednesday, and Friday, then no afegostat tartrate on Tuesday, Thursday, Saturday, and Sunday (MWF 3-days-on/4-days-off). Once Amendment 2 was implemented at a site, participants assigned to the 7-days-on/7-days-off regimen switched to a 3-days-on/4-days-off regimen; those on the original 3-days-on/4-days-off regimen could switch to the MWF 3-days-on/4-days-off regimen. Amendment 4 removed the original 3-days-on/4-days-off regimen and any participants still on that regimen switched to the MWF 3-days-on/4-days-off regimen. Study visits occurred every 3 months for 30 months. Participants were contacted approximately 1, 3, and 6 months after the end of treatment (EOT) or early termination for follow-up assessments.

Afegostat tartrate was administered orally at a dose of 225 mg QD for 3 or 7 consecutive days followed by no study medication for 4 or 7 consecutive days (consecutive 3-days-on/4-days-off or 7-days-on/7-days-off, respectively). Amendment 2 added a MWF 3-days-on/4-days-off regimen. After Amendment 2 was implemented, all participants were assigned to one of the two 3-days-on/4-days-off regimens. Amendment 4 removed the consecutive 3-days-on/4-days-off regimen, and all participants were assigned to the MWF 3-days-on/4-days-off regimen. Participants were to receive afegostat tartrate for 30 months and be followed for 6 months after EOT.

A TEAE was defined as any adverse event (AE) with start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe AE defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through the end of follow-up is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Standard MRI procedures were used to measure the volume of the spleen. The baseline value was defined as the value recorded on Days 1 to 3 of the study (certain values could have been carried over from the last assessment in the lead-in study, GAU-CL-202). A negative change from Baseline indicates that spleen volume decreased.

Standard MRI procedures were used to measure the volume of the liver. The baseline value was defined as the value recorded on Days 1 to 3 of the study (certain values could have been carried over from the last assessment in the lead-in study, GAU-CL-202). A negative change from Baseline indicates that liver volume decreased.

Inclusion Criteria: Male or female participants, 18 years of age or older Completed study GAU-CL-202 with no significant protocol violations or safety concerns Clinically stable Had not received enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) in the past 12 months and was willing not to initiate ERT or SRT during study participation Agreed to practice an acceptable method of contraception Provided written informed consent to participate in the study Exclusion Criteria: During the screening period, had any clinically significant findings which would compromise the safety of the participant, or preclude the participant from completing the study as deemed by the investigator Had a clinically significant disease, severe complications from Gaucher disease, or serious intercurrent illness that may preclude participation in the study, in the opinion of the Investigator Had a history of allergy or sensitivity to the study drug or any excipients, including any prior serious allergic reaction to iminosugars (for example, miglustat) Had a pacemaker or other contraindication for magnetic resonance imaging scanning Was pregnant or breast-feeding Had current gastrointestinal, liver, or kidney disease, sequelae of these diseases, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs Participant was otherwise unsuitable for the study in the opinion of the Investigator