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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

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Gaucher Disease Drug: Velaglucerase alfa Dietary Supplement: Vitamin D Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 19 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 7, 2016
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : January 30, 2021


Arm Intervention/treatment
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).
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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).

  8. 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).

  9. 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.

  10. 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".

  11. 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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02574286


Contacts
Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com

Locations
United States, California
Cedars Sinai Medical Center Completed
Beverly Hills, California, United States, 90211
Kaiser Permanente Completed
Los Angeles, California, United States, 90027
United States, Georgia
Emory Genetics Recruiting
Atlanta, Georgia, United States, 30322
Contact: Site contact    404-778-3543    jvengoe@emory.edu   
Principal Investigator: Jaime Vengoechea Barrios, MD         
United States, Illinois
Ann and Robert H Lurie Childrens Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Site contact    312-227-4000    jcharrow@northwestern.edu   
Principal Investigator: Joel Charrow, MD         
United States, New York
NYU School of Medicine Recruiting
New York, New York, United States, 10016
Contact: Site contact    212-263-8344    heather.lau@nyumc.org   
Principal Investigator: Heather Lau, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Site contact    919-681-9854    kishn001@mc.duke.edu   
Principal Investigator: Priya Kishnani, MD         
United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Site contact    215-590-3376    ficicioglu@email.chop.edu   
Principal Investigator: Can Ficicioglu         
Israel
Rambam Health Care Campus Recruiting
Haifa, Israel, 3109601
Contact: Site contact    +972-4-7772456    hb_feldman@rambam.health.gov.il   
Principal Investigator: Hagit Baris Feldman         
Shaare Zedek Medical Center Recruiting
Jerusalem, Israel, 91031
Contact: Site contact    +972 2 6555143    azimran@gmail.com   
Principal Investigator: Ari Zimmerman, MD         
Rabin Medical Center Recruiting
Petah Tikva, Israel, 49100
Contact: Site contact    +972-3-9377522    noa.ruhrman@clalit.org.il   
Principal Investigator: Noa Ruhrman Shahar         
Spain
Hospital Universitario Ramon y Cajal Recruiting
Madrid, Spain, 28034
Contact: Site contact    +34 6090053105    jesus.vallarrubia@salud.madrid.org   
Principal Investigator: Jesus Villarrubia Espinosa, MD, PhD         
Hospital Quironsalud Zaragoza Recruiting
Zaragoza, Spain, 50006
Contact: Site contact    +34 976765 546    giraldocastellano@gmail.com   
Principal Investigator: Pilar Giraldo, MD         
United Kingdom
Addenbrooke's Hospital Recruiting
Cambridge, United Kingdom, CB20QQ
Contact: Site contact    +44 01223 274634    patrick.deegan@addenbrookes.nhs.uk   
Principal Investigator: Patrick B Deegan, MD         
Royal Free Hospital Recruiting
London, United Kingdom, NW3 2QG
Contact: Site contact    +44 207 793 4154    rmgvdah@ucl.ac.uk   
Principal Investigator: Derralynn A Hughes, MD         
Sponsors and Collaborators
Shire
Investigators
Study Director: Study Director Shire

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02574286     History of Changes
Other Study ID Numbers: SHP-GCB-402
2015-001578-17 ( EudraCT Number )
First Posted: October 12, 2015    Key Record Dates
Last Update Posted: October 4, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Gaucher Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Vitamins
Vitamin D
Ergocalciferols
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents