A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease (ENGAGE)

Gaucher Disease, Type 1 Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study Confirming the Efficacy and Safety of Genz-112638 in Patients With Gaucher Disease Type 1 (ENGAGE)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00891202
• Other study ID #: GZGD02507
• Secondary ID: 2008-005222-37EF
• Status: Active, not recruiting
• Phase: Phase 3
• First received: April 30, 2009
• Last updated: October 16, 2015
• Start date: November 2009
• Est. completion date: November 2015

Study information

• Verified date: October 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationIndia: Drugs Controller General of IndiaRussia: Ministry of Health of the Russian FederationNetherlands: Medicines Evaluation Board (MEB)Canada: Health CanadaUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyMexico: Ministry of HealthBulgaria: Bulgarian Drug AgencyIsrael: Israeli Health Ministry Pharmaceutical AdministrationJordan: Ethical CommitteeTunisia: Office of Pharmacies and MedicinesColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosLebanon: Ministry of Public HealthChile: Ministry of HealthSerbia and Montenegro: Agency for Drugs and Medicinal Devices
• Study type: Interventional

Clinical Trial Summary

This Phase 3 study is designed to confirm the efficacy and safety of eliglustat tartrate (Genz-112638) in participants with Gaucher disease Type 1.

Description:

Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to impaired glucosylceramide hydrolysis. Type 1 Gaucher disease, the most common form accounts for greater than (>) 90% of cases and does not involve the central nervous system (CNS). Typical manifestations of Type 1 Gaucher disease include splenomegaly, hepatomegaly, thrombocytopenia, anemia, skeletal pathology and decreased quality of life. The disease manifestations are caused by the accumulations of glucosylceramide (storage material) in Gaucher cells which have infiltrated the spleen and liver as well as other tissue. Eliglustat tartrate is a small molecule developed as an oral therapy which acts to specifically inhibit production of this storage material in Gaucher cells.

This study is designed to determine the efficacy, safety, and pharmacokinetics (PK) of eliglustat tartrate in adult participants (>16 years) with Gaucher disease Type 1. The study consists of 2 periods: The Double-Blind Primary Analysis Period (Day 1 to Week 39) and the Open-Label Period (post-Week 39 [Day 1 of the Open-Label Period] through study completion).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: November 2015
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• The participant (and/or their parent/legal guardian) is willing and able to provide signed informed consent prior to any study-related procedures to be performed

• The participant is at least 16 years old at the time of randomization

• The participant has a confirmed diagnosis of Gaucher disease Type 1

• Female participants of childbearing potential must have a documented negative pregnancy test prior to dosing. In addition all female participants of childbearing potential must use a medically accepted form of contraception throughout the study

Exclusion Criteria:

• The participant has had a partial or total splenectomy

• The participant has received pharmacological chaperones or miglustat within 6 months prior to randomization

• The participant has received enzyme replacement therapy within 9 months prior to randomization

• The participant has Type 2 or 3 Gaucher disease or is suspected of having Type 3 Gaucher disease

• The participant has any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal (GI), pulmonary, neurologic, endocrine, metabolic, (for example, hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illness that may confound the study results, or, on the opinion of the investigator, may preclude participation in the study

• The participant has tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen

• The participant has received an investigational product within 30 days prior to randomization

• The participant 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
• Gaucher Disease, Type 1

Intervention

Drug:
• Eliglustat tartrate
Eliglustat tartrate capsule as a single 50 milligram (mg) dose on Day 1 followed by eliglustat tartrate 50 mg capsule twice daily (BID) from Day 2 to Week 4, and then either eliglustat tartrate 50 mg capsule BID (in participants who had a Genz-99067 [active moiety of eliglustat tartrate in plasma] trough plasma concentration greater than or equal to [>=] 5 nanogram per milliliter [ng/mL]) or eliglustat tartrate 100 mg capsule BID (in participants who had a Genz-99067 trough plasma concentration less than [<] 5 ng/mL), up to Week 39. The pharmacokinetic (PK) assessment at Week 2 was used for dose adjustment after Week 4.
• Placebo
Matching placebo capsule once daily on Day 1 followed by matching placebo capsule BID from Day 2 through Week 39.

Locations

Country	Name	City	State
Bulgaria	University hospital "Alexandrovska" Sofia	Sofia
Canada	Sir Mortimer B. Davis - Jewish General Hospital	Montreal, Quebec
Canada	Mount Sinai Hospital and the Samuel Lunenfeld Research Institute	Toronto Ontario
Colombia	Hospital de San Jose	Bogota
India	Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI)	Lucknow
India	Sir Ganga Ram Hospital	New Delhi
India	Christian Medical College Hospital	Vellore
Israel	Rabin Medical Center, Beilinson Hospital	Petach Tikvah
Jordan	King Abdullah University Hospital	Irbid
Lebanon	Hôtel-Dieu de France University Hospital	Beirut
Mexico	OCA Hospital	Monterrey, Nuevo Leon
Netherlands	Academic Medical Center, Department of Internal Medicine	Amsterdam
Russian Federation	Hematology Research Center of Ministry of Healthcare of the Russian Federation	Moscow
Serbia	Institut za endokrinologiju	Belgrade
Tunisia	Hopital La-Rabta	Tunis	TN
United Kingdom	Royal Free Hospital	London
United States	Emory University Medical Genetics	Decatur	Georgia
United States	Duke University Medical Center	Durham	North Carolina
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Mount Sinai School of Medicine	New York	New York
United States	New York University School of Medicine, Neurology Department	New York	New York
United States	UCSF MS Center	San Francisco	California
United States	O and O Alpan	Springfield	Virginia
United States	University of Kansas Medical Center, Division of Hematology/Oncology, Dept. of Medicine	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Colombia,  India,  Israel,  Jordan,  Lebanon,  Mexico,  Netherlands,  Russian Federation,  Serbia,  Tunisia,  United Kingdom, 

References & Publications (6)

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. — View Citation

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

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. — 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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Spleen Volume (in Multiples of Normal [MN]) at Week 39 of the Primary Analysis Period With Eliglustat Tartrate Treatment as Compared to Placebo	Percent change in spleen volume = ([spleen volume at Week 39 minus spleen volume at baseline] divided by [spleen volume at baseline]) multiplied by 100, where all volumes are in MN.	Baseline, Week 39	No
Secondary	Hemoglobin Level		Baseline	No
Secondary	Absolute Change From Baseline in Hemoglobin Level at Week 39	Absolute change = hemoglobin level at Week 39 minus hemoglobin level at baseline.	Baseline, Week 39	No
Secondary	Percent Change From Baseline in Liver Volume (in MN) at Week 39	Percent change in liver volume = ([liver volume at Week 39 minus liver volume at baseline] divided by [liver volume at baseline]) multiplied by 100, where all volumes are in MN.	Baseline, Week 39	No
Secondary	Percent Change From Baseline in Platelet Counts at Week 39	Percent change in platelet count = ([platelet count at Week 39 minus platelet count at baseline] divided by [platelet count at baseline]) multiplied by 100.	Baseline, Week 39	No