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

NCT02574286 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: SHP-GCB-4022015-001578-17
• Study Type: interventional
• Target: 21
• Locations: 4 countries
• Sites: 15

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 dual energy x-ray absorptiometry (DXA) after 24 months of treatment.

Conditions

Gaucher Disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-Score up to End of Study (EOS) (Week 103)

  Bone mineral density of the lumbar spine was measured by dual energy x-ray absorptiometry (DXA), and the results was converted to Z-scores appropriate for age, sex, and race. The Z-score indicated 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 was equal to the mean. Negative numbers indicated values lower than the mean and positive numbers indicated values higher than the mean. Baseline was defined as last data collected prior to the first administration of study drug. Change from baseline in lumbar spine BMD Z-Score up to EOS (Week 103) was reported.

  Baseline up to EOS (Week 103)

Secondary Outcomes (13)

• Change From Baseline in Lumbar Spine (LS) BMD Z-score at Week 51

  Baseline, Week 51

• Change From Baseline in Lumbar Spine BMD at Week 51 and EOS (Week 103)

  Baseline, Week 51 and EOS (Week 103)

• Change From Baseline in Total Bone Marrow Burden (BMB) Score at Week 51 and EOS (Week 103)

  Baseline, Week 51 and EOS (Week 103)

• Change From Baseline in Hemoglobin Concentration at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)

  Baseline, Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)

• Change From Baseline in Platelet Count at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)

  Baseline, Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)

Study Arms (1)

Velaglucerase alfa 60 U/kg

EXPERIMENTAL

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; Dietary Supplement: Vitamin D

Interventions

Velaglucerase alfa DRUG

Participants will receive 60-minute intravenous infusion of 60 U/kg velaglucerase alfa EOW.

Velaglucerase alfa 60 U/kg

Vitamin D DIETARY_SUPPLEMENT

Participants will receive 800 IU vitamin D orally daily.

Velaglucerase alfa 60 U/kg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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. (This criterion is not meant to exclude participants who have accessory spleens.)
• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (15)

Cedars Sinai Medical Center

Beverly Hills, California, 90211, United States

Location

Kaiser Permanente

Los Angeles, California, 90027, United States

Location

Emory Genetics

Atlanta, Georgia, 30322, United States

Location

Ann and Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

NYU School of Medicine

New York, New York, 10016, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Lysosomal and Rare Disorders Research and Treatment Center

Fairfax, Virginia, 22030, United States

Location

Rambam Health Care Campus

Haifa, 3109601, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Quironsalud Zaragoza

Zaragoza, 50006, Spain

Location

Addenbrooke's Hospital

Cambridge, CB20QQ, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

MeSH Terms

Conditions

Gaucher Disease

Interventions

Glucosylceramidase; Vitamin D

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Glucosidases; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2015
• First Posted: October 12, 2015
• Study Start: June 29, 2016
• Primary Completion: November 12, 2020
• Study Completion: November 30, 2020
• Last Updated: February 1, 2022
• Results First Posted: February 1, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

ES (2); IL (3); US (8); GB (2)