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A Study of the Efficacy and Safety of Eliglustat Tartrate (Genz-112638) in Type 1 Gaucher Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00358150
First received: July 27, 2006
Last updated: August 22, 2014
Last verified: August 2014
  Purpose

Gaucher disease is a genetic disease that results in a deficiency of an enzyme acid beta-glucosidase, also known as glucocerebrosidase. This enzyme is needed to digest a substrate (lipid) called glucosylceramide and, to a lesser degree, glucosylsphingosine. In participants with Gaucher disease, the liver, spleen, bone marrow and brain show increases in lipid concentration, specifically in cells derived from the monocyte/macrophage system.

Eliglustat tartrate (Genz-112638) is an oral drug that may regulate the Gaucher disease process by decreasing the synthesis of glucosylceramide. The primary objective of this study is to evaluate the efficacy, safety and pharmacokinetics (PK) of eliglustat tartrate, administered as an oral dose of either 50 milligram (mg) twice daily (BID) or 100 mg BID, to men and women with Gaucher disease Type 1 for 52 weeks.


Condition Intervention Phase
Gaucher Disease, Type 1
Cerebroside Lipidosis Syndrome
Glucocerebrosidase Deficiency Disease
Glucosylceramide Beta-Glucosidase Deficiency Disease
Gaucher Disease, Non-Neuronopathic Form
Drug: Eliglustat tartrate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Multi-Center Study Evaluating the Efficacy, Safety and Pharmacokinetics of Genz-112638 in Gaucher Type 1 Patients

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percentage of Participants Demonstrating A Meaningful Clinical Response [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    A meaningful clinical response was defined as an improvement in at least 2 of the 3 main efficacy parameters: a) an increase in hemoglobin of greater than or equal to (>=) 0.5 gram/deciliter from baseline, b) an increase in platelets of >=15 percent (%) from baseline, c) reduction in total spleen volume of >= 15% from baseline. As hemoglobin, platelets, total spleen volume were abnormal at baseline, within each participant, only those parameters were used in the evaluation of meaningful clinical response which were abnormal at baseline.


Secondary Outcome Measures:
  • Percent Change From Baseline in Spleen Volume at Month 48 [ Time Frame: Baseline, Month 48 ] [ Designated as safety issue: No ]
    Percent change in spleen volume = ([spleen volume at Month 48 minus spleen volume at baseline] divided by [spleen volume at baseline]) multiplied by 100, where all volumes are in multiples of normal.

  • Percent Change From Baseline in Liver Volume at Month 48 [ Time Frame: Baseline, Month 48 ] [ Designated as safety issue: No ]
    Percent change in liver volume = ([liver volume at Month 48 minus liver volume at baseline] divided by [liver volume at baseline]) multiplied by 100, where all volumes are in multiples of normal.

  • Absolute Change From Baseline in Hemoglobin at Month 48 [ Time Frame: Baseline, Month 48 ] [ Designated as safety issue: No ]
    Absolute change = hemoglobin level at Month 48 minus hemoglobin level at baseline.

  • Percent Change From Baseline in Platelet Count at Month 48 [ Time Frame: Baseline, Month 48 ] [ Designated as safety issue: No ]
    Percent change in platelet count = ([platelet count at Month 48 minus platelet count at baseline] divided by [platelet count at baseline]) multiplied by 100.


Other Outcome Measures:
  • Change From Baseline in Biomarkers (Angiotensin Converting Enzyme [ACE], Tartrate-Resistant Acid Phosphatase [TRAP], Chemokine Ligand 18 [CCL18], Chitotriosidase) at Month 48 [ Time Frame: Baseline, Month 48 ] [ Designated as safety issue: No ]
  • Participant Reported Quality of Life: Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey at Month 48 [ Time Frame: Baseline, Month 48 ] [ Designated as safety issue: No ]
  • Participant Reported Quality of Life: Fatigue Severity Scale Survey at Month 48 [ Time Frame: Baseline, Month 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Mobility, Bone Pain, and Bone Crisis at Month 48 [ Time Frame: Baseline, Month 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Radiographic Measures of Bone Disease at Month 48 [ Time Frame: Baseline, Month 48 ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: June 2006
Estimated Study Completion Date: December 2015
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eliglustat tartrate Drug: Eliglustat tartrate
Eliglustat (Genz-112638) capsule as single 50 milligram (mg) dose on Day 1 then eliglustat 50 mg twice daily (BID) from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 nanogram per milliliter [ng/mL] on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Month 48. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Month 48. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme), and if all other causes for lack of treatment effect had been evaluated and ruled out).
Other Name: Genz-112638

Detailed Description:

This study consists of several phases: screening (-28 to -1 days), dose adjustment/treatment (Day 1 [treatment baseline] to Day 30), initial steady-state treatment (post-Day 30 through Week 52 post-baseline), a treatment interruption period (Week 52 through approximately Week 54), long-term steady-state treatment (approximately Week 54 through study completion), and safety follow-up (30 to 37 days after a participant withdraws from or completes the study). The Primary Analysis Period is from baseline through Week 52. The Extension Period is from Week 52 through study completion (that is, participant withdrawal, the study is terminated, eliglustat tartrate becomes commercially available, or where applicable, specific regulatory requirements have been met).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The participant has a diagnosis of Gaucher Type I disease and a documented deficiency of glucocerebrosidase activity by enzyme assay and is willing and able to provide written informed consent prior to initiating any study-related procedures
  • The participant is 18 to 65 years old and weighs between 50 and 120 kilogram (kg) at enrollment
  • The participant has the following symptoms of Gaucher disease identified within 28 days of enrollment (at screening):

    • Anemia - indicated by hemoglobin measurements taken during the screening phase (8 to 10 gram per deciliter (g/dL) if female, 8 to 11 g/dL if male)
    • Thrombocytopenia - indicated by platelet count measurements taken during the screening phase (60000 to 100000 per cubic millimeter)
    • Splenomegaly, as indicated by magnetic resonance imaging (MRI) or spiral computed tomography (CT) (>= 10 multiples of normal)
  • Female participants of child-bearing potential must have a documented negative serum pregnancy test prior to dosing. Female participants agree to use a reliable method of birth control throughout duration of trial

Exclusion Criteria:

  • Participant has had a partial or total splenectomy or infarcted areas of the spleen
  • Participant has documented prior bleeding varices or liver infarction
  • Participant received miglustat within 12 months prior to study enrollment
  • The participant has received an investigational product within 30 days prior to study enrollment
  • Participant has neurologic or pulmonary involvement
  • Participant has new pathological bone involvement or bone crisis in the 12 months prior to enrollment
  • Participant is transfusion-dependent
  • Participant has a documented etiology of anemia due to causes other than Gaucher disease
  • The participant has cardiac functional and/or anatomical abnormalities, a history of cancer or tested positive for human immunodeficiency virus (HIV) antibody or Hepatitis
  • Participant has a clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic, or psychiatric disease, other medical conditions, or serious intercurrent illnesses that, in the opinion of the Investigator, may preclude participation in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00358150

Locations
United States, New York
New York, New York, United States
New York University
New York, New York, United States
Argentina
Instituto Argentino de Diagnostico y Tratamiento (IADT)
Buenos Aires, Argentina
Aprillus Asistencia e Investigación
Buenos Aires, Argentina
Hospital de Oncologia Maria Curie
Buenos Aires, Argentina
IMAI
Buenos Aires, Argentina
Buenos Aires, Argentina
Hospital Ramos Mejia
Ciudad Autonoma de Buenos Aires, Argentina
Israel
Haifa, Israel
Rambam Medical Center
Haifa, Israel
Sha'are Zedek Medical Centre
Jerusalem, Israel
Jerusalem, Israel
Italy
Universita degli Studi di Milano
Milano, Italy
Mexico
Instituto Mexicano del Seguro Social
D.f., Mexico
Mexico City, Mexico
Russian Federation
Moscow, Russian Federation
Hematology Research Center of Ministry of Healthcare of the Russian Federation
Moscow, Russian Federation
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

Publications:
Peterschmitt MJ, Burke A, Blankstein L, Smith SE, Puga AC, Kramer WG, Harris JA, Mathews D, Bonate PL. Safety, Tolerability, and Pharmacokinetics of Eliglustat Tartrate (Genz-112638) After Single Doses, Multiple Doses, and Food in Healthy Volunteers. J Clin Pharmacol. 2010 Oct 25; [Epub ahead of print]

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00358150     History of Changes
Other Study ID Numbers: GZGD00304, 2005-004732-42
Study First Received: July 27, 2006
Results First Received: August 22, 2014
Last Updated: August 22, 2014
Health Authority: United States: Food and Drug Administration
Russia: Pharmacological Committee, Ministry of Health
Israel: Israeli Health Ministry Pharmaceutical Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Mexico: Federal Commission for Protection Against Health Risks

Keywords provided by Sanofi:
Type 1 Gaucher Disease
Glucocerebrosidase Deficiency Disease

Additional relevant MeSH terms:
Deficiency Diseases
Gaucher Disease
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lipidoses
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Malnutrition
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Nutrition Disorders
Sphingolipidoses

ClinicalTrials.gov processed this record on November 19, 2014