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A Study of Oral AT2101 in Treatment-Naive Patients With Gaucher Disease
This study is currently recruiting participants.
Verified by Amicus Therapeutics, November 2008
Sponsored by: Amicus Therapeutics
Information provided by: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT00446550
  Purpose

This study is being conducted to evaluate the safety and effects of AT2101 in patients with type I Gaucher disease who are not receiving ERT or SRT.


Condition Intervention Phase
Gaucher Disease, Type 1
Drug: AT2101
Phase II

Genetics Home Reference related topics: cholesteryl ester storage disease Farber lipogranulomatosis Gaucher disease long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency mitochondrial trifunctional protein deficiency primary carnitine deficiency
MedlinePlus related topics: Gaucher's Disease
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety Study
Official Title: A Randomized, Open-Label Study To Assess the Safety and Tolerability of AT2101 in Treatment-Naive Adult Patients With Type I Gaucher Disease

Further study details as provided by Amicus Therapeutics:

Primary Outcome Measures:
  • The primary objective of this study is to evaluate the safety and tolerability of AT2101. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The secondary objective of the study is to evaluate the pharmacodynamic effects of AT2101. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 16
Study Start Date: December 2007
Estimated Study Completion Date: May 2009
Estimated Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
AT2101 dose regimen 1
Drug: AT2101

Arm 1: AT2101 oral capsules, dose 1, regimen 1

Arm 2: AT2101 oral capsules, dose 1, regimen 2

2: Experimental
AT2101 dose regimen 2
Drug: AT2101

Arm 1: AT2101 oral capsules, dose 1, regimen 1

Arm 2: AT2101 oral capsules, dose 1, regimen 2


Detailed Description:

Gaucher disease is a lysosomal storage disorder resulting from a deficiency in the key enzyme beta-glucocerebrosidase (GCase). The enzyme deficiency is caused by genetic mutations, which can result in the production of misfolded GCase. AT2101 is designed to act as a pharmacological chaperone by selectively binding to the misfolded GCase and helping it fold correctly, which may restore GCase activity.

This study is being conducted to test the safety of AT2101 in patients with type I Gaucher disease who have not already received enzyme replacement therapy (ERT) or substrate reduction therapy (SRT), or who have not received ERT or SRT in the 12 months before screening. This study will also evaluate the effects of AT2101 on parameters that are commonly abnormal in Gaucher disease. The study will involve 9 visits over 29 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of type 1 Gaucher disease with a known genotype and a documented missense gene mutation in at least one of the two mutated GBA alleles
  • Clinically stable
  • Treatment naïve to enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) or has not received ERT or SRT in the 12 months before screening
  • Willing not to initiate ERT or SRT treatment during study participation
  • At the screening period visit, subjects must meet at least two of the following criteria:
  • Platelet count of ≤ 150,000 per microliter
  • Hemoglobin ≤ 12 g/dL for females and ≤13 g/dL for males
  • Liver volume ≥ 1.25 multiples of normal
  • Spleen volume ≥ 2 multiples of normal
  • All subjects of reproductive potential are required to practice an acceptable method of contraception
  • Provide written informed consent to participate in the study

Exclusion Criteria:

  • A clinically significant disease, severe complications from Gaucher disease, or serious illness that may preclude participation in the study in the opinion of the Investigator
  • During the screening period, 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 (PAP) > 35 mmHg or significant Gaucher related lung disease
  • History of allergy or sensitivity to the study drug or any excipients, including any prior serious adverse reaction to iminosugars
  • Pacemaker or other contraindication for 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00446550

Locations
United States, California
University of California San Francisco Not yet recruiting
San Francisco, California, United States, 94143-0749
Contact: Seymour Packman, MD     415-476-2871     spackman@peds.ucsf.edu    
Principal Investigator: Seymour Packman, MD            
Tower Hematology Oncology Medical Group - Comprehensive Gaucher Treatment Center Recruiting
Beverly Hills, California, United States, 90211
Contact: Cheryl Elzinga     888-248-4456     ElzingaC@toweroncology.com    
Principal Investigator: Barry Rosenbloom, MD            
United States, Florida
University Research Foundation for Lysosomal Storage Diseases, Inc. Recruiting
Coral Springs, Florida, United States, 33065
Contact: Lisa Constantin     954-755-1904 ext 115     lisa@nwoncology.com    
Principal Investigator: Neal Weinreb, MD            
United States, Georgia
Emory University Lysosomal Storage Disease Ctr Recruiting
Decatur, Georgia, United States, 30033
Contact: Karen Grinzaid     404-778-8565     kgrinzaid@genetics.emory.edu    
Principal Investigator: Paul Fernhoff, MD            
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Myrl Holida     319-356-2007     myrl-holida@uiowa.edu    
Principal Investigator: Thomas Loew, MD            
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Majed Dasouki, MD     913-588-6326     mdasouki@kumc.edu    
Principal Investigator: Majed Dasouki, MD            
United States, Massachusetts
Genetics & Metabolism Center for Human Genetics Recruiting
Boston, Massachusetts, United States, 02114
Contact: Virginia Clarke     617-726-8830     vclarke1@partners.org    
Principal Investigator: Marsha Browning, MD            
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Lisa Hostetler     612-825-7422     hoste005@umn.edu    
Principal Investigator: Chester Whitley, MD PhD            
United States, New York
New York University School of Medicine Not yet recruiting
New York, New York, United States, 10016
Contact: Michele Ford     212-263-8344     Michele.Ford@nyumc.org    
Principal Investigator: Greg Pastores, MD            
United States, Ohio
Lysosomal Storage Disease Center Not yet recruiting
Cincinnati, Ohio, United States, 45229
Contact: Laurie Bailey     513-636-4507     laurie.bailey@cchmc.org    
Principal Investigator: Nancy Leslie, MD            
United States, Pennsylvania
Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Michele Graham     800-334-7980     michele.graham@chp.edu    
Principal Investigator: David Feingold, MD            
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Kathy Gilmartin     267-426-5441     gilmartin@email.chop.edu    
Principal Investigator: Can Ficicioglu, MD            
Germany
Universitats-Kinderklinik Recruiting
Mainz, Germany, 55101
Contact: Michael Beck, MD     49 6131 172398     beck@kinder.klinik.uni-mainz.de    
Principal Investigator: Michael Beck, MD            
Israel
Rambam Health Care Campus - Hematology and Bone Marrow Transplant Department Recruiting
Haifa, Israel
Contact: Hanna Rosenbaum, MD     972-4-8542343     h_rosenbaum@rambam.health.gov.il    
Principal Investigator: Hanna Rosenbaum, MD            
Schneider Children's Medical Center of Israel Recruiting
Petah-Tikvah, Israel
Contact: Talli Shrieber     972-3-9253781     tallish@clalit.org.il    
Principal Investigator: Ian Cohen, MD            
United Kingdom
Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust Recruiting
Cambridge, United Kingdom, CB2 2QQ
Contact: Elizabeth Morris     44 1223 336864     liz.morris@addenbrookes.nhs.uk    
Principal Investigator: Timothy Cox, MD, PhD            
The Royal Free Hospital Recruiting
London, United Kingdom, WC1N 3BG
Contact: Alan Milligan     44 2074 726409     alan.milligan@royalfree.nhs.uk    
Principal Investigator: Atul Mehta, MD            
Sponsors and Collaborators
Amicus Therapeutics
Investigators
Study Director: Eugene Schneider, MD Amicus Therapeutics
  More Information

Responsible Party: Amicus Therapeutics ( Eugene Schneider, MD / Medical Director, Clinical Research )
Study ID Numbers: GAU-CL-202
Study First Received: March 9, 2007
Last Updated: November 24, 2008
ClinicalTrials.gov Identifier: NCT00446550  
Health Authority: United States: Food and Drug Administration;   United Kingdom: Medicines and Healthcare Products Regulatory Agency;   Germany: Federal Institute for Drugs and Medical Devices;   Israel: Ministry of Health

Study placed in the following topic categories:
Lipid Metabolism, Inborn Errors
Sphingolipidoses
Metabolic Diseases
Lysosomal Storage Diseases
Sphingolipidosis
Central Nervous System Diseases
Brain Diseases
Lymphatic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Brain Diseases, Metabolic, Inborn
Lipidoses
Metabolic disorder
Gaucher Disease
Lipid Metabolism Disorders
Brain Diseases, Metabolic

Additional relevant MeSH terms:
Reticuloendotheliosis
Lysosomal Storage Diseases, Nervous System
Nervous System Diseases

ClinicalTrials.gov processed this record on January 16, 2009