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

NCT01074944 | Completed Phase 3 Results DMC

• 3 other identifiers: GZGD031092009-015811-42EFC12818
• Study Type: interventional
• Target: 170
• Locations: 15 countries
• Sites: 42

Brief Summary

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

Conditions

Gaucher Disease

Keywords

Gaucher disease; Genz-112638; beta-glucosidase; acid β-glucosidase; glucocerebrosidase; glucosylceramide; D-glucosyl-N-acylsphingosine glucohydrolase; substrate reduction therapy

Outcome Measures

Primary Outcomes (1)

• PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP

  Participants were considered as stable if they met all of the following criteria: 1) no more than 2 bone crisis during PAP (with no more than 1 bone crisis during either the first 6 months or the later 6 months of the period), and were free of other clinically symptomatic bone disease during the entire 52-week PAP; 2) hemoglobin level not decreased \>1.5 g/dL from Baseline for PAP; 3) platelet count not decreased \>25% from Baseline for PAP; 4) spleen volume (in multiples of normal \[MN\]) did not increase \>25% from Baseline for PAP; 5) liver volume (in MN) did not increase \>20% from Baseline for PAP. Baseline for PAP was defined as the last assessment prior to randomization.

  PAP Baseline up to the end of PAP (Week 52)

Secondary Outcomes (35)

• PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52

  Baseline, Week 26, Week 52

• PAP: Mean Platelet Count at Baseline, Weeks 26, 52

  Baseline, Week 26, Week 52

• PAP: Mean Spleen Volume at Baseline, Weeks 26, 52

  Baseline, Week 26, Week 52

• PAP: Mean Liver Volume at Baseline, Weeks 26, 52

  Baseline, Week 26 and Week 52

• PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52

  Baseline, Week 26, Week 52

Study Arms (2)

Twice Daily (BID) Dose Regimen

EXPERIMENTAL

Patients will receive either 50 mg BID or 100 mg BID

Drug: Eliglustat tartrate

Once Daily (QD) Dose Regimen

EXPERIMENTAL

Patients will receive either 100 mg QD or 200 mg QD

Drug: Eliglustat tartrate

Interventions

Eliglustat tartrate DRUG

Oral Capsule in 50 mg or 100 mg dosages

Also known as: Genz-112638

Once Daily (QD) Dose Regimen; Twice Daily (BID) Dose Regimen

Eligibility Criteria

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

You may qualify if:

• The participant who was willing and provided signed informed consent prior to any study-related procedures.
• The participant was ≥18 years of age.
• The participant diagnosed with GD 1 confirmed by a documented deficiency of acid β-glucosidase activity by enzyme assay.
• Female participants of childbearing potential had a documented negative pregnancy test prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study. In addition, all female participants of childbearing potential used 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
• The participant met all of the following criteria at the time of screening: hemoglobin level ≥9 g/dL (mean of 2 measurements); platelet count ≥70,000/mm\^3 (mean of 2 measurements); spleen volume ≤25 multiples of normal (MN); liver volume ≤2.0 MN.
• The participant consented to provide a blood sample for genotyping for Gaucher disease and for CYP2D6 to categorize the participant's predicted rate of metabolism, if these genotyping results were not already available for the participant.
• The participant was willing to abstain from consumption of grapefruit, grapefruit juice, or grapefruit products for 72 hours prior to administration of the first dose of Genz-112638 and throughout the duration of the study.

You may not qualify if:

• The participant received miglustat within 6 months prior to administration of the first dose of Genz-112638 in this study.
• The participant had a partial or total splenectomy within 3 years prior to randomization.
• The participant received pharmacological chaperones or miglustat within 6 months prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study.
• The participant had any evidence of neurologic disorder (e.g., peripheral neuropathy, tremor, seizures, Parkinsonism or cognitive impairment) or pulmonary involvement (e.g., pulmonary hypertension) as related to Gaucher disease.
• The participant was transfusion-dependent.
• The participant had a documented deficiency of iron, vitamin B-12, or folate that requires treatment not yet initiated or, if initiated, the participant had not been stable under treatment for at least 3 months prior to administration of the first dose of Genz-112638 in this study.
• The participant had documented prior esophageal varices or clinically significant liver infarction or current liver enzymes (alanine transaminase \[ALT\]/aspartate aminotransferase \[AST\]) or total bilirubin \>2 times the upper limit of normal (ULN), unless the participant had a diagnosis of Gilbert Syndrome.
• The participant had 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, precluded participation in the study.
• The participant was known to have any of the following: Clinically significant coronary artery disease including history of myocardial infarction \[MI\] or ongoing signs or symptoms consistent with cardiac ischemia or heart failure; or clinically significant arrhythmias or conduction defect such as 2nd or 3rd degree AV block, complete bundle branch block, prolonged QTc interval, or sustained ventricular tachycardia (VT).
• The participant who tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen.
• The participant 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 participant was scheduled for in-participant hospitalization, including elective surgery, during the study.
• The participant had a history of cancer, with the exception of basal cell carcinoma, within 5 years prior to administration of the first dose of Genz-112638 in this study.
• The participant was pregnant or lactating.
• The participant had received any medication that may cause QTc interval prolongation within 30 days prior to the first dose of Genz-112638. Exception: Diphenhydramine (Benadryl) or other medications used as premedication for ERT infusions were allowed up to 7 days prior to the first dose of Genz-112638.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (46)

University of California, San Diego Medical Center

San Diego, California, United States

Location

Yale University School of Medicine

New Haven, Connecticut, United States

Location

Emory University Medical Center

Decatur, Georgia, United States

Location

Children's Memorial Hospital

Chicago, Illinois, United States

Location

Mount Sinai Medical Center

New York, New York, United States

Location

New York University School of Medicine

New York, New York, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Location

University of Utah

Salt Lake City, Utah, United States

Location

O and O Alpan LLC

Springfield, Virginia, United States

Location

Royal Prince Alfred Hospital

Camperdown, Australia

Location

Monash Medical Centre

Clayton, VIC, Australia

Location

Royal Perth Hospital

Perth, WA, Australia

Location

Medical University Vienna

Vienna, Austria

Location

Hospital das Clinicas da UFMG

Belo Horizonte, Brazil

Location

Cettro - Centro de Tratamento de Oncologia e Hematologia

Brasília, Brazil

Location

Hemocentro - UNICAMP

Campinas, Brazil

Location

Instituto Tropical de Medicina Reprodutiva e Menopausa - INTRO

Cuiabá, Brazil

Location

Hospital Universitario Walter Cantidio - HUWC

Fortaleza, Brazil

Location

Hemocentro de Ribeirão Preto Núcleo de Hemoterapia de Franca

Franca, Brazil

Location

Hemorio

Rio de Janeiro, Brazil

Location

Hospital de Clínicas da Universidade Federal do Parana

São Paulo, Brazil

Location

IGEIM - Institute of Genetic and Inborn Erros of Metabolism

São Paulo, Brazil

Location

Mount Sinai Hospital

Toronto, Canada

Location

Peking Union Medical College Hospital

Beijing, China

Location

Peking University People's Hospital

Beijing, China

Location

Shanghai Xinhua Hospital Shanghai Xinhua Hospital

Shanghai, China

Location

Tianjin Hematonosis Hospital

Tianjin, China

Location

University Hospital Centre Zagreb

Zagreb, Croatia

Location

Hôpital Haut Lévêque

Bordeaux, France

Location

Hôpital Femme Mère Enfant Centre de référence des maladies Héréditaires du métabolisme

Bron, France

Location

General Hospital of Athens "G. Gennimatas"

Athens, Greece

Location

King Edward Memorial (KEM) Hospital

Mumbai, India

Location

Hiroshima University Hospital

Hiroshima, Japan

Location

Jikei University Hospital

Tokyo, Japan

Location

Juntendo University Hospital

Tokyo, Japan

Location

Mie Chuou Medical Center

Tsu, Mie, Japan

Location

Academic Medical Center

Amsterdam, Netherlands

Location

Hospital de Santa Maria

Lisbon, Portugal

Location

Hospital do Divíno Espírito Santo

Ponta Delgada - São Miguel - Açores, Portugal

Location

Spitaulu Clinic de Urgenta

Cluj-Napoca, Romania

Location

State Medical and Prophylactic Healthcare Institution; Chelyabinsk Regional Clinical Hospital

Chelyabinsk, Russia

Location

Hematology Research Center of Russian Academy of Medical Sciences

Moscow, Russia

Location

St. Petersburg State Medical Pavlov University

Saint Petersburg, Russia

Location

Clinical Centre of Serbia

Belgrade, Serbia

Location

University Hospital Lund

Lund, Sweden

Location

Related Publications (4)

• 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. doi: 10.1016/j.ymgme.2007.04.001. Epub 2007 May 16.

  PMID: 17509920 BACKGROUND

• 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.

  PMID: 20439622 BACKGROUND

• 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.

  PMID: 20713962 BACKGROUND

• Charrow J, Fraga C, Gu X, Ida H, Longo N, Lukina E, Nonino A, Gaemers SJM, Jouvin MH, Li J, Wu Y, Xue Y, Peterschmitt MJ. Once- versus twice-daily dosing of eliglustat in adults with Gaucher disease type 1: The Phase 3, randomized, double-blind EDGE trial. Mol Genet Metab. 2018 Mar;123(3):347-356. doi: 10.1016/j.ymgme.2017.12.001. Epub 2018 Jan 4.

  PMID: 29358012 DERIVED

Related Links

• 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

MeSH Terms

Conditions

Gaucher Disease

Interventions

eliglustat

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: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2010
• First Posted: February 24, 2010
• Study Start: June 1, 2010
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: February 6, 2017
• Results First Posted: December 2, 2016

Record last verified: 2016-12

Locations

SE (1); AU (1); RO (1); CN (4); US (10); CA (1); JP (4); NL (1); FR (2); GR (1); BR (9); RU (3); CR (1); IN (1); PT (2)