A Study of Oral AT2101 (Afegostat Tartrate) in Treatment-naive Patients With Gaucher Disease

NCT00446550 | Completed Phase 2 Results DMC

• 1 other identifier: GAU-CL-202
• Study Type: interventional
• Target: 19
• Locations: 4 countries
• Sites: 11

Brief Summary

This study evaluated the safety and tolerability of afegostat tartrate in participants with type 1 Gaucher disease who were not receiving enzyme replacement therapy (ERT) or substrate reduction therapy (SRT).

Conditions

Gaucher Disease; Type 1 Gaucher Disease; Gaucher Disease, Type 1

Keywords

Amicus Therapeutics; afegostat tartrate; isofagomine tartrate; AT2101

Outcome Measures

Primary Outcomes (1)

• Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)

  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 (Day 183) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

  Day 1 (after dosing) through Day 183

Secondary Outcomes (1)

• Change From Baseline To End Of Treatment In β-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)

  Baseline, Day 169

Study Arms (2)

Afegostat Tartrate Treatment Regimen 1

EXPERIMENTAL

For the first 2 weeks, afegostat tartrate was administered orally at a dose of 225 milligrams (mg) once daily (QD) for 7 consecutive days, followed by no study medication for 7 consecutive days. After 2 weeks, participants then took 225 mg afegostat tartrate QD for 3 consecutive days, followed by no study medication for 4 consecutive days. This 3-days-on/4-days-off treatment regimen was followed for 22 weeks.

Drug: afegostat tartrate

Afegostat Tartrate Treatment Regimen 2

EXPERIMENTAL

Afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. This 7-days-on/7-days-off treatment regimen was followed for 24 weeks.

Drug: afegostat tartrate

Interventions

afegostat tartrate DRUG

Also known as: isofagomine tartrate, AT2101

Afegostat Tartrate Treatment Regimen 1; Afegostat Tartrate Treatment Regimen 2

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of type 1 Gaucher disease with a known genotype and a documented missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase (GBA) alleles
• Clinically stable
• Treatment naïve to ERT and SRT or had not received ERT or SRT in the 12 months before screening
• Willing to not initiate ERT or SRT treatment during study participation
• Male or female participants, 18 to 74 years old, inclusive
• At the screening period (Day -21 to Day -1), participants must have met at least 2 of the following criteria: platelet count of ≤150,000 per microliter, hemoglobin ≤12 grams/deciliter (g/dL) for females and ≤13 g/dL for males, liver volume ≥1.25 multiples of normal (MN), and spleen volume ≥2 MN
• All participants of reproductive potential were required to practice an acceptable method of contraception
• Provided written informed consent to participate in the study

You may not qualify if:

• A clinically significant disease other than Gaucher disease, severe complications from Gaucher disease, or serious intercurrent illness that precluded participation in the study in the opinion of the investigator
• During the screening period, had any clinically significant findings as deemed by the investigator
• Partial or total splenectomy
• Documentation of moderate or severe pulmonary hypertension, defined as pulmonary arterial pressure \>35 millimeters of mercury (mmHg) or significant Gaucher-related lung disease
• History of allergy or sensitivity to the study drug or any excipients, including any prior serious allergic reaction to iminosugars
• Pacemaker or other contraindication for magnetic resonance imaging (MRI) scanning
• Pregnant or breast-feeding
• Current/recent drug or alcohol abuse
• Treatment with any investigational product in the last 90 days before study entry
• Treatment in the previous 90 days with any drug known to have a well-defined potential for toxicity to a major organ
• Presence of symptoms of gastrointestinal, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs

Sponsors & Collaborators

• Amicus Therapeutics: lead

Study Sites (11)

Unknown Facility

Beverly Hills, California, 90211, United States

Location

Unknown Facility

Coral Springs, Florida, 33065, United States

Location

Unknown Facility

Decatur, Georgia, 30033, United States

Location

Unknown Facility

Iowa City, Iowa, 52242, United States

Location

Unknown Facility

Kansas City, Kansas, 66160, United States

Location

Unknown Facility

Boston, Massachusetts, 02114, United States

Location

Unknown Facility

Cincinnati, Ohio, 45229, United States

Location

Unknown Facility

Haifa, Israel

Location

Unknown Facility

Tel Aviv, Israel

Location

Unknown Facility

Johannesburg, South Africa

Location

Unknown Facility

London, United Kingdom

Location

MeSH Terms

Conditions

Gaucher Disease

Interventions

AT2101

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Results Point of Contact

• Title: Amicus Therapeutics
• Organization: Patient Advocacy

Clinicaltrials@amicusrx.com

+1-609-662-2000

Study Officials

• Medical Monitor, Clinical Research

  Amicus Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2007
• First Posted: March 13, 2007
• Study Start: June 11, 2008
• Primary Completion: August 20, 2009
• Study Completion: August 20, 2009
• Last Updated: August 15, 2018
• Results First Posted: August 15, 2018

Record last verified: 2018-07

Locations

US (7); ZA (1); IL (2); GB (1)