Gaucher DiseasePhase 3NCT01074944
A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease to Evaluate Once Daily Versus Twice Daily Dosing (EDGE)
A Phase 3 study testing Eliglustat tartrate in people with Gaucher Disease, run by Genzyme, a Sanofi Company at 46 sites in 17 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gaucher Disease
- What is being tested?
- Eliglustat tartrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 46 sitesin 17 countries
- Study dates
- Jun 2010to Oct 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- The participant was participating in GZGD02607 study, "A Phase 3, Randomized, Multi-Center, Multi-National, Open-Label, Active Comparator Study to Evaluate the Efficacy and Safety of Genz-112638 in Participants with GD1 who have been Stabilized with Cerezyme ® ," or was eligible for inclusion in GZGD02607 (while enrollment was ongoing) and had access to a physician participating in GZGD02607, or the participant was participating in GZGD02507 study, "A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study Confirming the Efficacy and Safety of Genz-112638 in Participants with GD1," or was eligible for inclusion in GZGD02507 (while enrollment was ongoing) and had access to a physician participating in GZGD02507.
- 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.
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- 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.
- The participant had received for the first time (i.e., the participant was not already chronically using) any of the following medications within 30 days prior to the first dose of Genz-112638:
- Strong inhibitors of CYP2D6 or CYP3A4;
- Inducers of CYP3A4. Exception: Premedications for ERT infusions were allowed up to 7 days prior to the first dose of Genz-112638.
- The participant was a CYP2D6 non-poor metabolizer or an indeterminate metabolizer with one allele identified as active who was chronically receiving both a strong competitive inhibitor of CYP2D6 and a strong competitive inhibitor of CYP3A4 and for whom no reasonable alternative medication exists. or
- The participant was a CYP2D6 poor metabolizer or an indeterminate metabolizer with neither allele known to be active who was chronically receiving a strong competitive inhibitor of CYP3A4 and for whom no reasonable alternative medication exists.
- Exception for both cases: Premedications for ERT infusions were allowed up to 7 days prior to the first dose of Genz-112638.
Trial locations and contacts
46 sites in 17 countries.
46 sites in 17 countries
United States10 sites
Children's Memorial Hospital
Chicago, Illinois
Emory University Medical Center
Decatur, Georgia
Yale University School of Medicine
New Haven, Connecticut
Mount Sinai Medical Center
New York, New York
New York University School of Medicine
New York, New York
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania
University of Utah
Salt Lake City, Utah
University of California, San Diego Medical Center
San Diego, California
O and O Alpan LLC
Springfield, Virginia
Brazil9 sites
Hospital das Clinicas da UFMG
Belo Horizonte
Cettro - Centro de Tratamento de Oncologia e Hematologia
Brasília
Hemocentro - UNICAMP
Campinas
Instituto Tropical de Medicina Reprodutiva e Menopausa - INTRO
Cuiabá
Hospital Universitario Walter Cantidio - HUWC
Fortaleza
Hemocentro de Ribeirão Preto Núcleo de Hemoterapia de Franca
Franca
Hemorio
Rio de Janeiro
Hospital de Clínicas da Universidade Federal do Parana
São Paulo
IGEIM - Institute of Genetic and Inborn Erros of Metabolism
São Paulo
China4 sites
Peking Union Medical College Hospital
Beijing
Peking University People's Hospital
Beijing
Shanghai Xinhua Hospital Shanghai Xinhua Hospital
Shanghai
Tianjin Hematonosis Hospital
Tianjin
Japan4 sites
Hiroshima University Hospital
Hiroshima
Jikei University Hospital
Tokyo
Juntendo University Hospital
Tokyo
Mie Chuou Medical Center
Tsu, Mie
Australia3 sites
Royal Prince Alfred Hospital
Camperdown
Monash Medical Centre
Clayton, VIC
Royal Perth Hospital
Perth, WA
Russia3 sites
State Medical and Prophylactic Healthcare Institution; Chelyabinsk Regional Clinical Hospital
Chelyabinsk
Hematology Research Center of Russian Academy of Medical Sciences
Moscow
St. Petersburg State Medical Pavlov University
Saint Petersburg
France2 sites
Hôpital Haut Lévêque
Bordeaux
Hôpital Femme Mère Enfant Centre de référence des maladies Héréditaires du métabolisme
Bron
Portugal2 sites
Hospital de Santa Maria
Lisbon
Hospital do Divíno Espírito Santo
Ponta Delgada - São Miguel - Açores
About this study
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
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).
Read the detailed description
NOTE: Other Phase 3 studies being conducted with eliglustat tartrate (Genz-112638) are GZGD02507 (ENGAGE): NCT00891202 and GZGD02607 (ENCORE): NCT00943111
- Conditions
- Gaucher Disease
- Being tested
- Eliglustat tartrate
- Keywords
- Gaucher disease, Genz-112638, beta-glucosidase, acid β-glucosidase, glucocerebrosidase, glucosylceramide, D-glucosyl-N-acylsphingosine glucohydrolase, substrate reduction therapy
- Medical subject headings
- Gaucher Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eliglustat tartrateDrug
Also called Genz-112638
Oral Capsule in 50 mg or 100 mg dosages
| Study group | Role | What they receive |
|---|---|---|
| Twice Daily (BID) Dose Regimen | Experimental | Patients will receive either 50 mg BID or 100 mg BID Receives: Drug: Eliglustat tartrate |
| Once Daily (QD) Dose Regimen | Experimental | Patients will receive either 100 mg QD or 200 mg QD Receives: Drug: Eliglustat tartrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: PAP Baseline up to the end of PAP (Week 52)
Secondary outcomes (35)
PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52
Measured: Baseline, Week 26, Week 52
PAP: Mean Platelet Count at Baseline, Weeks 26, 52
Measured: Baseline, Week 26, Week 52
PAP: Mean Spleen Volume at Baseline, Weeks 26, 52
Measured: Baseline, Week 26, Week 52
PAP: Mean Liver Volume at Baseline, Weeks 26, 52
Measured: Baseline, Week 26 and Week 52
PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52
Chitotriosidase biomarker was assayed from plasma.
Measured: Baseline, Week 26, Week 52
PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52
GL-1 on DBS biomarker was assayed from dried blood spot (DBS).
Measured: Baseline, Week 26 and week 52
PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52
MIP1-beta biomarker was assayed from plasma.
Measured: Baseline, Week 26, Week 52
PAP: Bone Mineral Density (BMD) at Baseline and Week 52
BMD measurements of the spine and bilateral femur were acquired by dual-energy x-ray absorptiometry (DXA) scan.
Measured: Baseline, Week 52
PAP: Total T-Scores for BMD at Baseline and Week 52
Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. The T-score bone density categories were: normal (score >-1), osteopenia (score -2.5 to <=-1), and osteoporosis (score <= -2.5).
Measured: Baseline, Week 52
PAP: Total Z-scores for BMD at Baseline and Week 52
Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score >-2) and below normal (score <=-2).
Measured: Baseline, Week 52
PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.
Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported.
Measured: Baseline, Week 26 and Week 52
PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52
Bone crisis was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crisis, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crisis, 1= 1 bone crisis, and 2= 2 bone crises during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported.
Measured: Baseline, Week 26, and Week 52
PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52
Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain during the past 4 weeks. In this outcome, number of participants with different level of bone pain during the past 4 weeks at specified time points were reported.
Measured: Baseline, Week 26, and Week 52
PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52
BMB Score was measured using magnetic resonance imaging (MRI), range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0 (no abnormalities) -16 (severe disease) points. A higher BMB score signified more severe bone marrow involvement.
Measured: Baseline, Week 52
LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78
Measured: Baseline, Week 26, Week, 52, and Week 78
LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78
Measured: Baseline, Week 26, Week 52, Week 78
LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78
Measured: Baseline, Week 26, Week 52, Week 78
LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78
Measured: Baseline, Week 26, Week 52, Week 78
LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78
Chitotriosidase biomarker was assayed from plasma.
Measured: Baseline, Week 26, Week 52 and Week 78
LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78
GL-1 on DBS biomarker was assayed from dried blood spot.
Measured: Baseline, Week 26, Week 52 and Week 78
LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78
MIP1-beta biomarker was assayed from plasma.
Measured: Baseline and Week 78
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported.
Measured: Baseline, Week 26, Week 52, Week 78
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone crises was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crisis, 1= 1 bone crisis, 2= 2 bone crises, 6= 6 bone crises, and 24= 24 bone crises during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported.
Measured: Baseline, Week 26, Week 52, Week 78
LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78
Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain. In this outcome, number of participants with different type of bone pain during the past 4 weeks at specified time points were reported.
Measured: Baseline, Week 26, Week 52, Week 78
LTTP: Percentage of Participants Who Maintained a Stable Bone Criterion ,Hemoglobin Level, Platelet Count, Liver Volume and Spleen Volume at 1 Year and 2 Years
Participant were considered as stable if they met the following criteria: hemoglobin level did not decrease >1.5 g/dL from baseline for PAP, platelet count does not decrease >25% below Baseline for PAP, liver volume does not increase >20% above Baseline for PAP, spleen volume does not increase >25% above Baseline for PAP. Baseline for PAP was defined as last available assessment prior to randomization.
Measured: 1 Year, 2 Years
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported.
Measured: Baseline, 1 year, and 2 years
LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years
Bone crises was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crises, 1= 1 bone crisis during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported.
Measured: Baseline, 1 year and 2 years
LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years
Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain. In this outcome, number of participants with different level of bone pain during the past 4 weeks at specified time points were reported.
Measured: Baseline, 1 year and 2 years
LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years
BMD measurements of the spine and bilateral femur were acquired by DXA scan.
Measured: Baseline, 1 year, and 2 years
LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years
Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. The T-score bone density categories were: normal (score >-1), osteopenia (score -2.5 to <=-1), and osteoporosis (score <= -2.5).
Measured: Baseline, 1 year, and 2 years
LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years
Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score >-2) and below normal (score <=-2).
Measured: Baseline, 1 year, and 2 years
LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years
BMB Score was measured using MRI, range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0 (no abnormalities) -16 (severe disease) points. A higher BMB score signified more severe bone marrow involvement.
Measured: Baseline, 1 year, and 2 years
LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years
Chitotriosidase biomarker was assayed from plasma.
Measured: Baseline, 1 year, and 2 years
LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years
GL-1 on DBS biomarker was assayed from dried blood spot.
Measured: Baseline, 1 year, and 2 years
LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years
MIP1-beta biomarker was assayed from plasma.
Measured: Baseline, 1 year, and 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2010 (estimated)
- Study startJun 2010
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Gaucher DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01074944
- Sponsor's protocol ID
- GZGD03109
- Other IDs
- 2009-015811-42, EFC12818, 2009
- Status last verified
- Dec 2016
- First submitted
- 23 Feb 2010
- Last updated
- 6 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 17509920Lukina 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.
PubMed 20439622Lukina 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.
PubMed 20713962Charrow 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.
PubMed 29358012
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01074944
- Acronym / sponsor ID
- GZGD03109
- Conditions
- Gaucher Disease
- Keywords
- Gaucher disease, Genz-112638, beta-glucosidase, acid β-glucosidase, glucocerebrosidase, glucosylceramide, D-glucosyl-N-acylsphingosine glucohydrolase, substrate reduction therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Jun 2010
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 24 Feb 2010 (estimated)
- Results
- Posted 2 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
NOTE: Other Phase 3 studies being conducted with eliglustat tartrate (Genz-112638) are GZGD02507 (ENGAGE): NCT00891202 and GZGD02607 (ENCORE): NCT00943111
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Twice Daily (BID) Dose Regimen | Experimental | Drug: Eliglustat tartratePatients will receive either 50 mg BID or 100 mg BID |
| Once Daily (QD) Dose Regimen | Experimental | Drug: Eliglustat tartratePatients will receive either 100 mg QD or 200 mg QD |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (22 listed)
- The participant was participating in GZGD02607 study, "A Phase 3, Randomized, Multi-Center, Multi-National, Open-Label, Active Comparator Study to Evaluate the Efficacy and Safety of Genz-112638 in Participants with GD1 who have been Stabilized with Cerezyme ® ," or was eligible for inclusion in GZGD02607 (while enrollment was ongoing) and had access to a physician participating in GZGD02607, or the participant was participating in GZGD02507 study, "A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study Confirming the Efficacy and Safety of Genz-112638 in Participants with GD1," or was eligible for inclusion in GZGD02507 (while enrollment was ongoing) and had access to a physician participating in GZGD02507.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eliglustat tartrateAlso: Genz-112638Oral Capsule in 50 mg or 100 mg dosages | Drug | Once Daily (QD) Dose Regimen, Twice Daily (BID) Dose Regimen |
Primary outcome
PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP
Time frame: PAP Baseline up to the end of PAP (Week 52)
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.
35 secondary outcomes
PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52
Time frame: Baseline, Week 26, Week 52
PAP: Mean Platelet Count at Baseline, Weeks 26, 52
Time frame: Baseline, Week 26, Week 52
PAP: Mean Spleen Volume at Baseline, Weeks 26, 52
Time frame: Baseline, Week 26, Week 52
PAP: Mean Liver Volume at Baseline, Weeks 26, 52
Time frame: Baseline, Week 26 and Week 52
PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52
Time frame: Baseline, Week 26, Week 52
PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52
Time frame: Baseline, Week 26 and week 52
PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52
Time frame: Baseline, Week 26, Week 52
PAP: Bone Mineral Density (BMD) at Baseline and Week 52
Time frame: Baseline, Week 52
PAP: Total T-Scores for BMD at Baseline and Week 52
Time frame: Baseline, Week 52
PAP: Total Z-scores for BMD at Baseline and Week 52
Time frame: Baseline, Week 52
PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.
Time frame: Baseline, Week 26 and Week 52
PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52
Time frame: Baseline, Week 26, and Week 52
PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52
Time frame: Baseline, Week 26, and Week 52
PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52
Time frame: Baseline, Week 52
LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78
Time frame: Baseline, Week 26, Week, 52, and Week 78
LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78
Time frame: Baseline, Week 26, Week 52, Week 78
LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78
Time frame: Baseline, Week 26, Week 52, Week 78
LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78
Time frame: Baseline, Week 26, Week 52, Week 78
LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78
Time frame: Baseline, Week 26, Week 52 and Week 78
LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78
Time frame: Baseline, Week 26, Week 52 and Week 78
LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78
Time frame: Baseline and Week 78
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
Time frame: Baseline, Week 26, Week 52, Week 78
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Time frame: Baseline, Week 26, Week 52, Week 78
LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78
Time frame: Baseline, Week 26, Week 52, Week 78
LTTP: Percentage of Participants Who Maintained a Stable Bone Criterion ,Hemoglobin Level, Platelet Count, Liver Volume and Spleen Volume at 1 Year and 2 Years
Time frame: 1 Year, 2 Years
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
Time frame: Baseline, 1 year, and 2 years
LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years
Time frame: Baseline, 1 year and 2 years
LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years
Time frame: Baseline, 1 year and 2 years
LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years
Time frame: Baseline, 1 year, and 2 years
LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years
Time frame: Baseline, 1 year, and 2 years
LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years
Time frame: Baseline, 1 year, and 2 years
LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years
Time frame: Baseline, 1 year, and 2 years
LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years
Time frame: Baseline, 1 year, and 2 years
LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years
Time frame: Baseline, 1 year, and 2 years
LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years
Time frame: Baseline, 1 year, and 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17509920McEachern 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.
- Background: PubMed 20439622Lukina 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.
- Background: PubMed 20713962Lukina 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.
- Derived from this study: PubMed 29358012Charrow 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.
- GZGD02507 (NCT00891202) eliglustat tartrate (Genz-112638) Phase 3 Clinical Study in untreated patients with Gaucher disease type 1Link provided by the sponsor.
- GZGD02607 (NCT00943111) eliglustat tartrate (Genz-112638) Phase 3 Clinical Study in patients with Gaucher disease type 1 who have been stabilized on CerezymeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Genzyme, a Sanofi Company
46 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eliglustat tartrate in people with Gaucher Disease, run by Genzyme, a Sanofi Company at 46 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in United States, Brazil, China, Japan, Australia and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP (time frame: PAP Baseline up to the end of PAP (Week 52)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01074944, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2017.