A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE)
Condition: Gaucher Disease, Type 1
MeSH terms: Gaucher Disease
Intervention: Eliglustat tartrate; Imiglucerase
Intervention description: Primary analysis period (PAP): Eliglustat tartrate capsule 50 milligram (mg) twice daily (BID) orally from Day 1 to Week 4 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 8, and then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to Week 52. Dose adjustments after Week 4 and Week 8 were based on Genz-99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. If Genz-99067 trough plasma concentration was less than (<) 5 nanogram per milliliter [ng/mL] next higher dose was administered whereas if Genz-99067 trough plasma concentration was greater than or equal to (>=) 5 ng/mL same dose was continued. Pharmacokinetic (PK) assessment at Week 2 and 6 were used for dose adjustment after Week 4 and Week 8, respectively.
Long-term treatment period (LTTP): Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6.; PAP: Imiglucerase intravenous infusion every other week (q2w) up to Week 52 in doses equivalent to participant's past ERT dose prior to any unanticipated treatment interruption, dose reduction, or regimen change.
LTTP: Participants originally randomized to imiglucerase received eliglustat tartrate capsule 50 mg BID orally from Week 52+1 Day to Week 56 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 60, and then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to 5 years. The dose adjustments after Week 56 and Week 60 were based on Genz-99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. If Genz-99067 trough plasma concentration was <5 ng/mL the next higher dose was administered whereas if the Genz-99067 trough plasma concentration was >=5 ng/mL the same dose was continued. The PK assessment at Week 54 and Week 58 were used for dose adjustment after Week 56 and Week 60, respectively.
Intervention MeSH terms: Eliglustat
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 160.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gaucher disease,; Genz-112638,; beta-glucosidase,; acid ß-glucosidase,; glucocerebrosidase,; glucosylceramide,; D-glucosyl-N-acylsphingosine glucohydrolase,; substrate reduction therapy

Summary:

      This Phase 3 study was designed to confirm the efficacy and safety of eliglustat tartrate
      (Genz-112638) in participants with Gaucher disease type 1 who had reached therapeutic goals
      with enzyme replacement therapy (ERT).
    

Eligibility criteria:

        Inclusion Criteria:

          -  The participant (and/or their parent/legal guardian) was willing and able to provide
             signed informed consent prior to any study-related procedures to be performed

          -  The participant was at least 18 years old at the time of randomization

          -  The participant had a confirmed diagnosis of Gaucher disease type 1

          -  The participant had received treatment with ERT for at least 3 years. Within the 9
             months prior to randomization, the participant had received a total monthly dose of 30
             to 130 Units/kilogram for at least 6 months

          -  The participant had reached Gaucher disease therapeutic goals prior to randomization

          -  Female participants of childbearing potential must have had 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 had a partial or total splenectomy within 3 years prior to
             randomization

          -  The participant had received substrate reduction therapies for Gaucher disease within
             6 months prior to randomization

          -  The participant had Gaucher disease type 2 or 3 or was suspected of having Gaucher
             disease type 3

          -  The participant had any clinically significant disease, other than Gaucher disease,
             including cardiovascular, renal, hepatic, gastrointestinal (GI), pulmonary,
             neurologic, endocrine, metabolic (e.g. hypokalemia, hypomagnesemia), or psychiatric
             disease, other medical conditions, or serious intercurrent illnesses that may confound
             the study results or, in the opinion of the Investigator, may preclude participation
             in the study

          -  The participant had tested positive for the human immunodeficiency virus (HIV)
             antibody, Hepatitis C antibody, or Hepatitis B surface antigen

          -  The participant had received an investigational product within 30 days prior to
             randomization

          -  The participant was pregnant or lactating