Clinical trial NCT02536755: Phase 3b Study to Evaluate Skeletal Response to Eliglustat in Adult Patients Who Completed Phase 2 or Phase 3 Studies
Official title: Open Label Interventional Multicenter Phase 3b Study to Evaluate Skeletal Response to Eliglustat in Adult Patients Who Successfully Completed the Phase 2 or Phase 3 Studies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gaucher Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2015-09-01
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objective:

Evaluate long term skeletal response to eliglustat in adult participants who successfully completed one of the Phase 2 or Phase 3 eliglustat studies.

Secondary Objective:

Evaluate the safety of eliglustat (by serious adverse event continuous monitoring), the quality of life (Short Form-36 Health Survey \[SF-36\]) and biomarkers of Gaucher disease type 1 (GD1) (chitotriosidase, plasma glucosylceramide \[GL-1\] and lyso glucosylceramide \[lyso-GL-1\]) in adult participants who successfully completed one of the Phase 2 or Phase 3 studies.

Detailed description: Study duration for individual participants was to be of minimum 2 years and up to 4 years, or until commercial eliglustat was available to participants through reimbursement. If after 4 years since the beginning of the study eliglustat was not approved and available to participants in participating country, participants in this country might continue to receive study treatment until eliglustat was available to participants through the compassionate use (expanded access) program or was approved and available through reimbursement, whichever came first.

Eligibility criteria: Inclusion criteria :

* The participant must have successfully completed the Phase 2 (GZGD00304) or a Phase 3 study (GZGD02507, GZGD02607 or GZGD03109). Successful completion was defined as participants enrolled in one of the above mentioned studies who received eliglustat through the end of the study and completed the end-of-study visit without having discontinued or been withdrawn prematurely.
* The participant was willing and able to provide signed informed consent prior to any protocol-required procedures being performed.
* Female participants of childbearing potential must have had a documented negative pregnancy test prior to enrollment and while they were receiving eliglustat treatment.
* Female participants of childbearing potential must have been willing to practice true abstinence in line with their preferred and usual lifestyle, or used a medically accepted form of contraception (either a barrier method, such as condom or diaphragm + spermicide, or a non-barrier method such as oral, injected, or implanted hormonal methods, or an intra-uterine device or system) while receiving eliglustat.

Exclusion criteria:

* The participant was unwilling to comply with the requirements of the protocol.
* The participant had received an investigational product (other than eliglustat) within 30 days prior to enrollment.
* The participant had received miglustat within the 6 months prior to enrollment.
* The participant had documented prior esophageal varices or liver infarction or current liver enzymes (alanine transaminase, aspartate aminotransferase) or total bilirubin greater than (\>)2 times the upper limit of normal, 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 (eg, hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses that might preclude participation in the study.
* The participant was known to have any of the following: cardiac disease (congestive heart failure, recent acute myocardial infarction, bradycardia, heart block, ventricular arrhythmia), long QT syndrome, or current treatment with Class IA or Class III antiarrhythmic medicinal products.
* The participant had tested positive for the human immunodeficiency virus antibody, hepatitis C antibody, or hepatitis B surface antigen.
* The participant had a history of cancer within 6 months of enrolment, with the exception of basal cell carcinoma.
* Participant was a CYP2D6 IM, EM or URM and was taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor.
* Participant was a CYP2D6 PM having taken a strong CYP3A inhibitor within 2 weeks prior to enrolment.
* If a female participant of childbearing potential had a positive pregnancy test (blood β-human chorionic gonadotropin \[β-HCG\]) or was breastfeeding prior to first dosing of eliglustat in this study, the participant could not enroll in the study at that time, but might have been rescreened after the end of the pregnancy, and/or when she was no longer breast feeding, provided rescreening took place before the end of the enrollment period.
* Women of childbearing potential who were unwilling or unable to be tested for pregnancy.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Number of Participants With Mobility Status Assessments at Study Baseline, Weeks 52, 104, 156 and 208
timeFrame: Study Baseline, Weeks 52, 104, 156 and 208
measure: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Study Baseline, Weeks 52, 104, 156 and 208
timeFrame: Study Baseline, Weeks 52, 104, 156 and 208
measure: Number of Participants With Bone Crisis at Study Baseline, Weeks 52, 104, 156 and 208
timeFrame: Study Baseline, Weeks 52, 104, 156 and 208
measure: Change From Current Study Baseline in Total Bone Marrow Burden (BMB) Scores at Weeks 52, 104, 156 and 208
timeFrame: Study Baseline, Weeks 52, 104, 156 and 208
measure: Change From Eliglustat Baseline in Total Bone Marrow Burden (BMB) Scores at Weeks 52, 104, 156 and 208
timeFrame: Eliglustat Baseline, Weeks 52, 104, 156 and 208 of the current study
measure: Change From Current Study Baseline in Total Spine and Femur Bone Mineral Density (BMD) at Weeks 52, 104, 156 and 208
timeFrame: Study Baseline, Weeks 52, 104, 156 and 208
measure: Change From Eliglustat Baseline in Total Spine and Femur Bone Mineral Density (BMD) at Weeks 52, 104, 156 and 208
timeFrame: Eliglustat Baseline, Weeks 52, 104, 156 and 208 of the current study
measure: Change From Current Study Baseline in Spine and Femur Total T-Scores for BMD at Weeks 52, 104, 156 and 208
timeFrame: Study Baseline, Weeks 52, 104, 156 and 208
measure: Change From Eliglustat Baseline in Spine and Femur Total T-Scores for BMD at Weeks 52, 104, 156 and 208
timeFrame: Eliglustat Baseline, Weeks 52, 104, 156 and 208 of the current study
measure: Change From Current Study Baseline in Spine and Femur Total Z-Scores for BMD at Weeks 52, 104, 156 and 208
timeFrame: Study Baseline, Weeks 52, 104, 156 and 208
measure: Change From Eliglustat Baseline in Spine and Femur Total Z-Scores for BMD at Weeks 52, 104, 156 and 208
timeFrame: Eliglustat Baseline, Weeks 52, 104, 156 and 208 of the current study
measure: Total Number of New or Worsening Osteonecrosis Events for Spine and Femur at Study Baseline, Week 52, 104, 156 and 208
timeFrame: Study Baseline, Weeks 52, 104, 156 and 208
measure: Total Number of New or Worsening Fracture Events for Spine and Femur at Study Baseline, Week 52, 104, 156 and 208
timeFrame: Study Baseline, Weeks 52, 104, 156 and 208
measure: Total Number of New or Worsening Infarcts Events for Spine and Femur at Study Baseline, Week 52, 104, 156 and 208
timeFrame: Study Baseline, Weeks 52, 104, 156 and 208
measure: Total Number of New or Worsening Lytic Lesions Events for Spine at Study Baseline, Week 104, and 208
timeFrame: Study Baseline, Weeks 104, and 208
measure: Observed Annual Incidence Rate for Spine and Femur Osteonecrosis at Week 52, 104, 156 and 208
timeFrame: For 52 Weeks (i.e., 1 year),104 Weeks (i.e., 2 year), 156 Weeks (i.e., 3 year) and 208 Weeks (i.e., 4 years)
measure: Observed Annual Incidence Rate for Spine and Femur Fracture at Week 52, 104, 156 and 208
timeFrame: For 52 Weeks (i.e., 1 year),104 Weeks (i.e., 2 year), 156 Weeks (i.e., 3 year) and 208 Weeks (i.e., 4 years)
measure: Observed Annual Incidence Rate for Spine and Femur Infarcts at Week 52, 104, 156 and 208
timeFrame: For 52 Weeks (i.e., 1 year),104 Weeks (i.e., 2 year), 156 Weeks (i.e., 3 year) and 208 Weeks (i.e., 4 years)
measure: Observed Annual Incidence Rate for Spine Lytic Lesion at Week 104, and 208
timeFrame: For 104 Weeks (i.e., 2 year), and 208 Weeks (i.e., 4 years)
measure: Change From Current Study Baseline in Bone Biomarker Level: Macrophage Inflammatory Protein 1 Beta (MIP-1β) at Weeks 26, 52, 78, 104, 130, 156,182, 208 and 234
timeFrame: Study Baseline, Weeks 26, 52, 78, 104, 130, 156, 182, 208 and 234
measure: Change From Eliglustat Baseline in Bone Biomarker Level: Macrophage Inflammatory Protein 1 Beta (MIP-1β) at Weeks 26, 52, 78, 104, 130, 156,182, 208 and 234
timeFrame: Eliglustat Baseline, Weeks 26, 52, 78, 104, 130, 156,182, 208 and 234 of the current study
measure: Change From Current Study Baseline in Bone Biomarker Level: Procollagen 1 N- Terminal Propeptide (P1NP) at Weeks 26, 52, 78, 104, 130, 156,182, 208 and 234
timeFrame: Study Baseline, Weeks 26, 52, 78, 104, 130, 156,182, 208 and 234
measure: Change From Eliglustat Baseline in Bone Biomarker Level: Procollagen 1 N- Terminal Propeptide (P1NP) at Weeks 26, 52, 78, 104, 130, 156,182, 208 and 234
timeFrame: Eliglustat Baseline, Weeks 26, 52, 78, 104, 130, 156,182, 208 and 234 of the current study
measure: Change From Current Study Baseline in Bone Biomarker Level: Type 1 Collagen C-Telopeptides (CTx) at Weeks 26, 52, 78, 104, 130, 156,182, 208 and 234
timeFrame: Study Baseline, Weeks 26, 52, 78, 104, 130, 156,182, 208 and 234
measure: Change From Eliglustat Baseline in Bone Biomarker Level: Type 1 Collagen C-Telopeptides (CTx) at Weeks 26, 52, 78, 104, 130, 156,182, 208 and 234
timeFrame: Eliglustat Baseline, Weeks 26, 52, 78, 104, 130, 156,182, 208 and 234 of the current study
Secondary outcomes:
measure: Change From Current Study Baseline in Gaucher Disease Type 1 (GD1) Biomarker Levels: Chitotriosidase at Week 26, 52, 78, 104, 130, 156, 182, 208 and 234
timeFrame: Study Baseline, Week 26, 52, 78, 104, 130, 156, 182, 208 and 234
measure: Change From Eliglustat Baseline in Gaucher Disease Type 1 (GD1) Biomarker Levels: Chitotriosidase at Week 26, 52, 78, 104, 130, 156, 182, 208 and 234
timeFrame: Eliglustat Baseline, Week 26, 52, 78, 104, 130, 156, 182, 208 and 234 of the current study
measure: Change From Current Study Baseline in GD1 Biomarker Levels: Glucosylceramide (GL-1) at Week 26, 52, 78, 104, 130, 156, 182, 208 and 234
timeFrame: Study Baseline, Week 26, 52, 78, 104, 130, 156, 182, 208 and 234
measure: Change From Eliglustat Baseline in GD1 Biomarker Levels: Glucosylceramide (GL-1) at Week 26, 52, 78, 104, 130, 156, 182, 208 and 234
timeFrame: Eliglustat Baseline, Week 26, 52, 78, 104, 130, 156, 182, 208 and 234 of the current study
measure: Change From Current Study Baseline in GD1 Biomarker Levels: Lyso Glucosylceramide (Lyso-GL-1) at Week 26, 52, 78, 104, 130, 156, 182, 208 and 234
timeFrame: Study Baseline, Week 26, 52, 78, 104, 130, 156, 182, 208 and 234
measure: Change From Eliglustat Baseline in GD1 Biomarker Levels: Lyso Glucosylceramide (Lyso-GL-1) at Week 26, 52, 78, 104, 130, 156, 182, 208 and 234
timeFrame: Eliglustat Baseline, Week 26, 52, 78, 104, 130, 156, 182, 208 and 234 of the current study
measure: Change From Current Study Baseline in Short Form-36 Health Survey (SF-36) Scores at Weeks 26, 52, 78, 104, 130, 156, 182, 208 and 234
timeFrame: Study Baseline, Weeks 26, 52, 78, 104, 130, 156, 182, 208 and 234
measure: Change From Eliglustat Baseline in SF-36 Scores at Weeks 26, 52, 78, 104, 130, 156, 182, 208 and 234
timeFrame: Eliglustat Baseline, Weeks 26, 52, 78, 104, 130, 156, 182, 208 and 234 of the current study
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From the first administration of the IMP to the last administration of the IMP + 5 days (up to 4 years, or until commercial eliglustat was available to participants through reimbursement or through the compassionate use [expanded access] program)
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Investigational Site Number 124002
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643001
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643002
city: Tunis
country: Tunisia
facility: Investigational Site Number 788001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: