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

NCT ID: NCT00358150

Last Updated: 2017-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2015-12-31

Brief Summary

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.

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).

Conditions

Gaucher Disease, Type 1; Cerebroside Lipidosis Syndrome; Glucocerebrosidase Deficiency Disease; Glucosylceramide Beta-Glucosidase Deficiency Disease; Gaucher Disease, Non-Neuronopathic Form

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Eliglustat tartrate

Group Type: EXPERIMENTAL

Eliglustat tartrate

Intervention Type: DRUG

Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg twice daily (BID) from Day 2 to Day 19, 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 Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing same treatment through study completion (Year 9). Participant receiving 100 mg BID could be considered for 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).

Interventions

Eliglustat tartrate

Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg twice daily (BID) from Day 2 to Day 19, 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 Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing same treatment through study completion (Year 9). Participant receiving 100 mg BID could be considered for 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).

Intervention Type: DRUG

Other Intervention Names

Genz-112638

Eligibility Criteria

Inclusion Criteria

• The participant had a diagnosis of Gaucher Type I disease and a documented deficiency of glucocerebrosidase activity by enzyme assay and was willing and able to provide written informed consent prior to initiating any study-related procedures;
• The participant was 18 to 65 years old and weighed between 50 and 120 kilogram (kg) at enrollment;
• The participant had 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 had a documented negative serum pregnancy test prior to dosing. Female participants agreed to use a reliable method of birth control throughout duration of trial.

Exclusion Criteria

• Participant had a partial or total splenectomy or infarcted areas of the spleen;
• Participant had documented prior bleeding varices or liver infarction;
• Participant received miglustat within 12 months prior to study enrollment;
• The participant had received an investigational product within 30 days prior to study enrollment;
• Participant had neurologic or pulmonary involvement;
• Participant had new pathological bone involvement or bone crisis in the 12 months prior to enrollment;
• Participant was transfusion-dependent;
• Participant had a documented etiology of anemia due to causes other than Gaucher disease;
• The participant had cardiac functional and/or anatomical abnormalities, a history of cancer or tested positive for human immunodeficiency virus (HIV) antibody or Hepatitis;
• Participant had 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, might preclude participation in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Genzyme, a Sanofi Company

Locations

New York University

New York, New York, United States

New York, New York, United States

Aprillus Asistencia e Investigación

Buenos Aires, , Argentina

Hospital de Oncologia Maria Curie

Buenos Aires, , Argentina

Hospital Ramos Mejia

Buenos Aires, , Argentina

IMAI

Buenos Aires, , Argentina

Instituto Argentino de Diagnostico y Tratamiento (IADT)

Buenos Aires, , Argentina

Buenos Aires, , Argentina

Rambam Medical Center

Haifa, , Israel

Haifa, , Israel

Sha'are Zedek Medical Centre

Jerusalem, , Israel

Jerusalem, , Israel

Universita degli Studi di Milano

Milan, , Italy

Instituto Mexicano del Seguro Social

D.f., , Mexico

Mexico City, , Mexico

Hematology Research Center of Ministry of Healthcare of the Russian Federation

Moscow, , Russia

Moscow, , Russia

Countries

United States; Argentina; Israel; Italy; Mexico; Russia

References

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.

Reference Type: BACKGROUND

PMID: 17509920 (View on PubMed)

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. 2011 May;51(5):695-705. doi: 10.1177/0091270010372387. Epub 2010 Sep 23.

Reference Type: BACKGROUND

PMID: 20864621 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20439622 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20713962 (View on PubMed)

Kamath RS, Lukina E, Watman N, Dragosky M, Pastores GM, Arreguin EA, Rosenbaum H, Zimran A, Aguzzi R, Puga AC, Norfleet AM, Peterschmitt MJ, Rosenthal DI. Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat. Skeletal Radiol. 2014 Oct;43(10):1353-60. doi: 10.1007/s00256-014-1891-9. Epub 2014 May 10.

Reference Type: RESULT

PMID: 24816856 (View on PubMed)

Lukina E, Watman N, Dragosky M, Pastores GM, Arreguin EA, Rosenbaum H, Zimran A, Angell J, Ross L, Puga AC, Peterschmitt JM. Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4 years of treatment. Blood Cells Mol Dis. 2014 Dec;53(4):274-6. doi: 10.1016/j.bcmd.2014.04.002. Epub 2014 May 15.

Reference Type: RESULT

PMID: 24835462 (View on PubMed)

Peterschmitt MJ, Foster MC, Ji AJ, Zajdel MB, Cox GF. Plasma glucosylsphingosine correlations with baseline disease burden and response to eliglustat in two clinical trials of previously untreated adults with Gaucher disease type 1. Mol Genet Metab. 2023 Mar;138(3):107527. doi: 10.1016/j.ymgme.2023.107527. Epub 2023 Jan 25.

Reference Type: DERIVED

PMID: 36739645 (View on PubMed)

Other Identifiers

2005-004732-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DRI12816

Identifier Type: OTHER

Identifier Source: secondary_id

GZGD00304

Identifier Type: -

Identifier Source: org_study_id