A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease to Evaluate Once Daily Versus Twice Daily Dosing (EDGE)

Gaucher Disease Clinical Trial

Official title:

A Phase 3, Randomized, Multi-Center, Multi-National, Double-Blind Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Once Daily Versus Twice Daily Dosing of Genz-112638 in Patients With Gaucher Disease Type 1 Who Have Demonstrated Clinical Stability on a Twice Daily Dose of Genz-112638

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01074944
• Other study ID #: GZGD03109
• Secondary ID: 2009-015811-42
• Status: Completed
• Phase: Phase 3
• First received: February 23, 2010
• Last updated: December 9, 2015
• Start date: June 2010
• Est. completion date: September 2015

Study information

• Verified date: December 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationCanada: Health CanadaChina: Food and Drug AdministrationCroatia: Ministry of Health and Social CareFrance: Ministry of HealthGreece: Ministry of Health and WelfareIndia: Drugs Controller General of IndiaJapan: Ministry of Health, Labor and WelfarePortugal: National Pharmacy and Medicines InstituteRussia: Pharmacological Committee, Ministry of HealthSerbia and Montenegro: Agency for Drugs and Medicinal DevicesSweden: The National Board of Health and WelfareNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Austria: Federal Office for Safety in Health CareRomania: National Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the efficacy and safety of once daily (QD) versus twice daily (BID) dosing of eliglustat tartrate (Genz-112638) in patients with Gaucher disease type 1 who have demonstrated clinical stability on BID dosing of eliglustat tartrate (Genz-112638). The secondary objective is to evaluate the pharmacokinetics (PK) of Genz-99067 when eliglustat tartrate (Genz-112638) is administered QD and BID in patients with Gaucher disease type 1 who have demonstrated clinical stability on BID dosing of eliglustat tartrate (Genz-112638).

Description:

NOTE: Other Phase 3 studies being conducted with eliglustat tartrate (Genz-112638) are GZGD02507 (ENGAGE): NCT00891202 and GZGD02607 (ENCORE): NCT00943111

Recruitment information / eligibility

• Status: Completed
• Enrollment: 171
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• The patient is willing and able to provide signed informed consent prior to any study-related procedures.

• The patient has a diagnosis of Gaucher disease type 1 confirmed by a documented deficiency of acid ß-glucosidase activity by enzyme assay.

• Female patients of childbearing potential must have a documented negative pregnancy test prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study. In addition, all female patients of childbearing potential must use a medically accepted form of contraception throughout the study, i.e., either a barrier method or hormonal contraceptive with norethindrone and ethinyl estradiol or similar active components.

Exclusion Criteria:

• The patient has had a partial or total splenectomy within 3 years prior to randomization.

• The patient received pharmacological chaperones or miglustat within 6 months prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study.

• The patient has any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic (including hypokalaemia or hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses that, in the opinion of the Investigator, may preclude participation in the study.

• The patient is known to have tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen.

• The patient has received an investigational product (other than eliglustat tartrate (Genz-112638)) within 30 days prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study.

• The patient is pregnant or lactating.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gaucher Disease

Intervention

Drug:
• eliglustat tartrate
Oral Capsule in 50 mg or 100mg dosages

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown
Australia	Monash Medical Centre	Clayton, VIC
Australia	Royal Perth Hospital	Perth, WA
Austria	Medical University Vienna	Vienna
Brazil	Hospital das Clinicas da UFMG	Belo Horizonte
Brazil	Cettro - Centro de Tratamento de Oncologia e Hematologia	Brasília
Brazil	Hemocentro - UNICAMP	Campinas
Brazil	Instituto Tropical de Medicina Reprodutiva e Menopausa - INTRO	Cuiaba
Brazil	Hospital Universitario Walter Cantidio - HUWC	Fortaleza
Brazil	Hemocentro de Ribeirão Preto Núcleo de Hemoterapia de Franca	Franca
Brazil	Hemorio	Rio de Janeiro
Brazil	Hospital de Clínicas da Universidade Federal do Parana	Sao Paulo
Brazil	IGEIM - Institute of Genetic and Inborn Erros of Metabolism	Sao Paulo
Canada	Mount Sinai Hospital	Toronto
China	Peking Union Medical College Hospital	Beijing
China	Peking University People's Hospital	Beijing
China	Shanghai Xinhua Hospital Shanghai Xinhua Hospital	Shanghai
China	Tianjin Hematonosis Hospital	Tianjin
Croatia	University Hospital Centre Zagreb	Zagreb
France	Hôpital Haut Lévêque	Bordeaux
France	Hôpital Femme Mère Enfant Centre de référence des maladies Héréditaires du métabolisme	Bron
Greece	General Hospital of Athens "G. Gennimatas"	Athens
India	King Edward Memorial (KEM) Hospital	Mumbai
Japan	Hiroshima University Hospital	Hiroshima
Japan	Jikei University Hospital	Tokyo
Japan	Juntendo University Hospital	Tokyo
Japan	Mie Chuou Medical Center	Tsu, Mie
Netherlands	Academic Medical Center	Amsterdam
Portugal	Hospital de Santa Maria	Lisboa
Portugal	Hospital do Divíno Espírito Santo	Ponta Delgada - São Miguel - Açores
Romania	Spitaulu Clinic de Urgenta	Cluj-Napoca
Russian Federation	State Medical and Prophylactic Healthcare Institution; Chelyabinsk Regional Clinical Hospital	Chelyabinsk
Russian Federation	Hematology Research Center of Russian Academy of Medical Sciences	Moscow
Russian Federation	St. Petersburg State Medical Pavlov University	St. Petersburg
Serbia	Clinical Centre of Serbia	Belgrade
Sweden	University Hospital Lund	Lund
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Emory University Medical Center	Decatur	Georgia
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Mount Sinai Medical Center	New York	New York
United States	New York University School of Medicine	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Utah	Salt Lake City	Utah
United States	University of California, San Diego Medical Center	San Diego	California
United States	O and O Alpan LLC	Springfield	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  Canada,  China,  Croatia,  France,  Greece,  India,  Japan,  Netherlands,  Portugal,  Romania,  Russian Federation,  Serbia,  Sweden, 

References & Publications (3)

Lukina E, Watman N, Arreguin EA, Banikazemi M, Dragosky M, Iastrebner M, Rosenbaum H, Phillips M, Pastores GM, Rosenthal DI, Kaper M, Singh T, Puga AC, Bonate PL, Peterschmitt MJ. A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood. 2010 Aug 12;116(6):893-9. doi: 10.1182/blood-2010-03-273151. Epub 2010 May 3. — View Citation

Lukina E, Watman N, Arreguin EA, Dragosky M, Iastrebner M, Rosenbaum H, Phillips M, Pastores GM, Kamath RS, Rosenthal DI, Kaper M, Singh T, Puga AC, Peterschmitt MJ. Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study. Blood. 2010 Nov 18;116(20):4095-8. doi: 10.1182/blood-2010-06-293902. Epub 2010 Aug 16. Erratum in: Blood. 2011 May 19;117(20):5551. — View Citation

McEachern KA, Fung J, Komarnitsky S, Siegel CS, Chuang WL, Hutto E, Shayman JA, Grabowski GA, Aerts JM, Cheng SH, Copeland DP, Marshall J. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease. Mol Genet Metab. 2007 Jul;91(3):259-67. Epub 2007 May 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of randomized patients who remain stable after treatment with eliglustat tartrate (Genz-112638) for both dosing regimens (BID full dose, QD full dose) separately, along with a difference between the two dosing regimens.		52 weeks	No
Secondary	Hemoglobin level		12 months	No
Secondary	Platelet count		12 months	No
Secondary	Spleen volume		12 months	No
Secondary	Liver volume		12 months	No
Secondary	Biomarkers		12 months	No
Secondary	Bone disease assessments		12 months	No
Secondary	Gaucher assessments (mobility, bone crisis, bone pain)		12 months	No

External Links

•   A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1
•   GZGD02507 (NCT00891202) eliglustat tartrate (Genz-112638) Phase 3 Clinical Study in untreated patients with Gaucher disease type 1
•   GZGD02607 (NCT00943111) eliglustat tartrate (Genz-112638) Phase 3 Clinical Study in patients with Gaucher disease type 1 who have been stabilized on Cerezyme