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

• ClinicalTrials.gov Identifier: NCT00813865
• Recruitment Status: Completed
• First Posted: December 23, 2008
• Results First Posted: August 15, 2018
• Last Update Posted: August 15, 2018
• Sponsor: Amicus Therapeutics
• Information provided by (Responsible Party): Amicus Therapeutics

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Gaucher Disease; Type 1 Gaucher Disease; Gaucher Disease, Type 1	Drug: afegostat tartrate	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 11, 2009
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm

Intervention/treatment

Experimental: Afegostat Tartrate Treatment Regimen 1; 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.

Drug: afegostat tartrate; Other Names: AT2101; isofagomine tartrate

Outcome Measures

Primary Outcome Measures :

1. Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Day 1 (after dosing) through end of follow-up (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.

Secondary Outcome Measures :

1. Change From Baseline To EOT In Volume Of Spleen As Assessed By Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline, Month 30 ]
   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.
2. Change From Baseline To EOT In Volume Of Liver As Assessed By MRI [ Time Frame: Baseline, Month 30 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Florida

Coral Springs, Florida, United States, 33065

United States, Georgia

Decatur, Georgia, United States, 30033

United States, Massachusetts

Boston, Massachusetts, United States, 02114

United Kingdom

London, United Kingdom

Sponsors and Collaborators

Amicus Therapeutics

Investigators

• Study Director: Medical Director; Amicus Therapeutics, Inc.

More Information

• Responsible Party: Amicus Therapeutics
• ClinicalTrials.gov Identifier: NCT00813865
• Other Study ID Numbers: GAU-CL-202X
• First Posted: December 23, 2008
• Results First Posted: August 15, 2018
• Last Update Posted: August 15, 2018
• Last Verified: July 2018

Keywords provided by Amicus Therapeutics:

Amicus Therapeutics; AT2101; afegostat tartrate; isofagomine tartrate

Additional relevant MeSH terms:

Gaucher Disease; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders