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Study of the Effect of Velaglucerase Alfa (VPRIV®) on Bone-related Pathology in Treatment-naïve Participants With Type 1 Gaucher Disease

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ClinicalTrials.gov Identifier: NCT02574286
Recruitment Status : Recruiting
First Posted : October 12, 2015
Last Update Posted : October 4, 2018
Sponsor:
Information provided by (Responsible Party):
Shire

October 9, 2015
October 12, 2015
October 4, 2018
June 7, 2016
December 30, 2020   (Final data collection date for primary outcome measure)
Change From Baseline in Lumbar Spine (LS) Bone Mineral Density (BMD) Z-Score to Week 103/End of Study [ Time Frame: Baseline, Week 103 (End of Study) ]
Bone mineral density of the lumbar spine will be measured by dual energy x-ray absorptiometry (DXA), and the results will be converted to Z-scores appropriate for age, sex, and race. The Z-score indicates the number of standard deviations away from a reference population in the same age range, race and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.
Change from baseline to 12 months (Week 51) in lumbar spine (LS) and Bone Mineral Density (BMD) Z-score as measured by DXA. [ Time Frame: Screening and Weeks 25, 51, 77, and 103 (end of study) ]
Complete list of historical versions of study NCT02574286 on ClinicalTrials.gov Archive Site
  • Change From Baseline in Lumbar Spine (LS) Bone Mineral Density (BMD) Z-score at Week 51 [ Time Frame: Baseline, Week 51 ]
    Bone mineral density of the lumbar spine will be measured by dual energy x-ray absorptiometry (DXA), and the results will be converted to Z-scores appropriate for age, sex, and race. The Z-score indicates the number of standard deviations away from a reference population in the same age range, race and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.
  • Change From Baseline in Bone Marrow Burden (BMB) Score [ Time Frame: Baseline, Weeks 51, 103 (End of Study) ]
    Bone marrow burden (BMB) score is a semi-quantitative MRI scoring system for assessing the extent of bone marrow involvement in Gaucher disease. BMB scores will be calculated from magnetic resonance imaging (MRI) of the LS and femurs, and will be converted to between 0 and 8. A higher BMB score indicates more severe bone marrow involvement.
  • Change From Baseline Over Time in Hemoglobin Concentration [ Time Frame: Baseline, Week 13, 25, 37, 51, 65, 77, 89, and 103 (end of study) ]
    Hemoglobin Concentration will be measured.
  • Change From Baseline Over Time in Platelet Count [ Time Frame: Baseline, Week 13, 25, 37, 51, 65, 77, 89, and 103 (end of study) ]
    Platelet count will be measured.
  • Change From Baseline in Normalized Liver Volume [ Time Frame: Baseline, Week 51 and 103 (end of study) ]
    Normalized liver volume will be measured by abdominal MRI.
  • Change From Baseline in Normalized Spleen Volume [ Time Frame: Baseline, Week 51 and 103 (end of study). ]
    Normalized spleen volume will be measured by MRI.
  • Change From Baseline in Severity of Bone Pain [ Time Frame: Baseline, Week 51 and 103 (end of study) ]
    Bone pain will be measured by the Brief Pain Inventory (BPI) (short form). The BPI is developed to assess the severity of pain and the impact of pain on daily functions. It will assess pain on scales for the severity of pain (0=No pain to 10=Pain as bad as you can imagine), impact of pain on daily function (0=Does not interfere to 10=Completely interferes), location of pain (area that hurts the most), pain medications (if any), and amount of pain relief in the past 24 hours or the past week (0=No relief to 100=Complete relief).
  • Change From Baseline in Impact of Bone Pain [ Time Frame: Baseline, Week 51 and 103 (end of study) ]
    Bone pain will be measured by the Brief Pain Inventory (BPI) (short form). The BPI is developed to assess the severity of pain and the impact of pain on daily functions. It will assess pain on scales for the severity of pain (0=No pain to 10=Pain as bad as you can imagine), impact of pain on daily function (0=Does not interfere to 10=Completely interferes), location of pain (area that hurts the most), pain medications (if any), and amount of pain relief in the past 24 hours or the past week (0=No relief to 100=Complete relief).
  • Change From Baseline in Overall Fatigue [ Time Frame: Baseline, Week 51 and 103 (end of study) ]
    Overall fatigue will be measured by the Brief Fatigue Inventory (BFI). The BFI is a 9-item questionnaire developed to assess subjective fatigue. Each question asks the respondent to rate the level of their experienced fatigue over the past 24 hours on an 11-point (0-10) scale. The first three questions measure fatigue severity at current, usual, and worst levels, respectively, with 0 indicating "no fatigue" and 10 indicating fatigue "as bad as you can imagine". The following six questions assess the level fatigue interference with daily activities including general activity, mood, walking ability, normal work (both inside and outside the home), relations with other people, and enjoyment of life. A score of 0 corresponds to no interference while a score of 10 indicates complete interference.
  • Shifts In World Health Organization (WHO) Bone Mineral Density (BMD) Classifications (Normal Bone Density, Osteopenia, Osteoporosis) Based on Lumbar Spine (LS) T-Scores [ Time Frame: Baseline, Week 51, and 103 (end of study) ]
    As per WHO BMD Classifications, bone mineral density will be classified based on LS T-scores as Normal for score "-1.0 or greater"; Low bone mass (osteopenia) for score "Between 1-.0 and .2.5"; Osteoporosis for score "-2.5 and below" and Severe osteoporosis for score "-2.5 and below + fragility fracture".
  • Number of Participants with Adverse Events (AEs) [ Time Frame: From start of study drug infusion up to 37 days after the last study drug infusion (106 weeks) ]
    An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.
  • Change from baseline to 12 months (Week 51) and 24 months (Week 103 [end of study]) in bone marrow burden (BMB) score (MRI of LS and femur). [ Time Frame: Baseline and Weeks 25, 51, 77, and 103 (end of study). ]
  • Change from baseline at 24 months (Week 103 [end of study]) in LS BMD Z-score. [ Time Frame: Baseline and Weeks 25, 51, 77, and 103 (end of study). ]
  • Change from baseline over time in hemoglobin concentration. [ Time Frame: Baseline and Weeks 7, 19, 31, 45, 57, 71, 83, and 95. ]
  • Change from baseline over time in platelet count. [ Time Frame: Baseline and Weeks 7, 19, 31, 45, 57, 71, 83, and 95. ]
  • Change from baseline to 12 months (Week 51) and 24 months (Week 103 [end of study]) in normalized liver volume as measured by abdominal MRI. [ Time Frame: Baseline visit and Weeks 25, 51, 77, and 103 (end of study). ]
  • Change from baseline to 12 months (Week 51) and 24 months (Week 103 [end of study]) in normalized spleen volume as measured by MRI. [ Time Frame: Baseline visit and Weeks 25, 51, 77, and 103 (end of study). ]
  • Change from baseline to 12 months (Week 51) and 24 months (Week 103 [end of study]) in bone pain as measured by the brief pain inventory (BPI). [ Time Frame: Baseline visit and Weeks 13, 25, 37, 51, 65, 77, 89, and 103 (end of study). ]
  • Change from baseline to 12 months (Week 51) and 24 months (Week 103 [end of study]) in overall fatigue as measured by the BFI. [ Time Frame: Baseline visit and Weeks 13, 25, 37, 51, 65, 77, 89, and 103 (end of study). ]
  • Shifts in World Health Organization (WHO) BMD classifications (normal bone density, osteopenia, osteoporosis) based on LS T-scores. [ Time Frame: Baseline (screening visit) and Weeks 25, 51, 77, and 103 (end of study). ]
  • Number of participants with Adverse Events (AEs) [ Time Frame: Screening through 30 day safety follow-up ]
Not Provided
Not Provided
 
Study of the Effect of Velaglucerase Alfa (VPRIV®) on Bone-related Pathology in Treatment-naïve Participants With Type 1 Gaucher Disease
An Open-label, Multicenter, Single-arm, Phase 4 Study of the Effect of Treatment With Velaglucerase Alfa on Bone-related Pathology in Treatment-naïve Patients With Type 1 Gaucher Disease
The primary purpose of this study is to evaluate the effect of VPRIV therapy (60 units per kilogram [U/kg] every other week [EOW]) in treatment-naive participants with type 1 Gaucher disease on change from baseline in lumbar spine (LS) bone mineral density (BMD) Z-score as measured by DXA after 24 months of treatment.
Not Provided
Interventional
Phase 4
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Gaucher Disease
  • Drug: Velaglucerase alfa
    Participants will receive 60-minute intravenous infusion of 60 U/kg velaglucerase alfa EOW.
  • Dietary Supplement: Vitamin D
    Participants will receive 800 IU vitamin D orally daily.
Experimental: Velaglucerase alfa 60 U/kg
Participants will receive 60-minute intravenous infusion of 60 units per kilogram (U/kg) velaglucerase alfa every other week (EOW) and an oral daily dose of 800 IU vitamin D for 24 months (101 weeks).
Interventions:
  • Drug: Velaglucerase alfa
  • Dietary Supplement: Vitamin D
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
19
40
January 30, 2021
December 30, 2020   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • The participant has a documented diagnosis of type 1 Gaucher disease, as documented by deficient GCB activity in leukocytes (whole blood only) or cultured skin fibroblasts. Diagnosis by only dry blood spot test is insufficient. Diagnosis may be based on results obtained prior to screening if documented in the participant's medical history.
  • Participants must have a LS BMD Z-score less than (<) -1 or BMD T-score of < -1 as measured by DXA during the screening phase.
  • Participant is treatment-naive, that is (ie,) has not received ERT or SRT in the 12 months prior to enrollment.
  • The participant is greater than or equal to (>=)18 and less than or equal to (<=) 70 years of age.
  • Female participants of childbearing potential must agree to use a medically acceptable method of contraception at all times during the study.
  • The participant, or participant's legally authorized representative(s), if applicable, understands the nature, scope, and possible consequences of the study and has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC).
  • The participant must be sufficiently cooperative to participate in this clinical study as judged by the investigator.

Exclusion criteria

  • Neurological symptoms indicating that the participant may have type 3 Gaucher disease.
  • A significant comorbidity, which, as determined by the investigator, might affect study data or confound the study results (eg, malignancies, primary biliary cirrhosis, autoimmune liver disease, etc).
  • Any osteoporosis-specific treatment (eg, bisphosphonates) or treatment with erythropoietin (or erythropoietin-like substances) during the past year.
  • Structural, joint-associated bone damage of such extent and severity that the investigator deems it could impact participation in the study and assessment of relevant study endpoints (example, pain).
  • The participant is pregnant or lactating.
  • The participant has had a splenectomy.
  • The participant is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or device) within 30 days prior to study enrollment or at any time during the study.
  • Severe vitamin D deficiency to the level that would be expected to result in osteomalacia (vitamin D < 10 nanograms per milliliter [ng/mL] [25 nanomoles per liter {nmol/L}]). If there is mild vitamin D insufficiency at screening (vitamin D greater than [>] 10 and < 30 ng/mL) treat with 4000 IU vitamin D per day for 1 month and rescreen.
  • The participant has previously interrupted ERT for safety reasons.
  • The participant has had hypersensitivity to the active substance or to any of the excipients.
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Older Adult)
No
Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com
Israel,   Spain,   United Kingdom,   United States
 
 
NCT02574286
SHP-GCB-402
2015-001578-17 ( EudraCT Number )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Shire
Shire
Not Provided
Study Director: Study Director Shire
Shire
October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP