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

January 3, 2022 updated by: Shire

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
21

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus
      • Jerusalem, Israel, 91031
        • Shaare Zedek Medical Center
      • Petah Tikva, Israel, 49100
        • Rabin Medical Center
  • Spain
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Zaragoza, Spain, 50006
        • Hospital Quironsalud Zaragoza
  • United Kingdom
      • Cambridge, United Kingdom, CB20QQ
        • Addenbrooke's Hospital
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital
  • United States
    • California
      • Beverly Hills, California, United States, 90211
        • Cedars Sinai Medical Center
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory Genetics
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann and Robert H Lurie Childrens Hospital of Chicago
    • New York
      • New York, New York, United States, 10016
        • NYU School of Medicine
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • The Children's Hospital of Philadelphia
    • Virginia
      • Fairfax, Virginia, United States, 22030
        • Lysosomal and Rare Disorders Research and Treatment Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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. (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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-Score up to End of Study (EOS) (Week 103)
Time Frame: Baseline up to 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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Lumbar Spine (LS) BMD Z-score at Week 51
Time Frame: Baseline, Week 51
BMD of the LS was measured by 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 LS BMD Z-score at Week 51 was reported. ITT Population was defined as all enrolled subjects who received at least one study drug infusion (full or partial). Here, "number of subjects analysed" signifies subjects who were evaluable for this endpoint.
Baseline, Week 51
Change From Baseline in Lumbar Spine BMD at Week 51 and EOS (Week 103)
Time Frame: Baseline, Week 51 and EOS (Week 103)
Bone mineral density of the LS was measured by DXA, and the results was measured in gram per square centimeter (g/cm^2). Baseline was defined as last data collected prior to the first administration of study drug. Change From baseline in LS BMD at Week 51 and EOS (Week 103) was reported.
Baseline, Week 51 and EOS (Week 103)
Change From Baseline in Total Bone Marrow Burden (BMB) Score at Week 51 and EOS (Week 103)
Time Frame: Baseline, Week 51 and EOS (Week 103)
BMB score was a semi-quantitative magnetic resonance imaging (MRI) scoring system for assessing the extent of bone marrow involvement in Gaucher disease. BMB Score was measured using magnetic resonance imaging (MRI), range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total BMB score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0 (no abnormalities) to 16 (severe disease) points. A higher BMB score signified more severe bone marrow involvement. Baseline was defined as last data collected prior to the first administration of study drug. Change from baseline in total BMB Score at Week 51 and EOS (Week 103) was reported.
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)
Time Frame: Baseline, Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)
Blood samples were collected for measurement of hemoglobin concentration. Baseline was defined as last data collected prior to the first administration of study drug. Change from baseline in hemoglobin concentration at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103) was reported.
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)
Time Frame: Baseline, Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)
Blood samples were collected for measurement of platelet count. Baseline was defined as last data collected prior to the first administration of study drug. Change from baseline over time in platelet count at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103) was reported.
Baseline, Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)
Change From Baseline in Normalized Liver Volume at Week 51 and EOS (Week 103)
Time Frame: Baseline, Week 51 and EOS (Week 103)
Normalized liver volume was measured by abdominal MRI. Baseline was defined as last data collected prior to the first administration of study drug. Liver volume has been normalized for percent (%) body weight. Liver size relative to body weight = (Liver volume [cubic centimeter (cc)]/Body weight [kg])*100. Change from baseline in normalized liver volume at Week 51 and EOS (Week 103) was reported.
Baseline, Week 51 and EOS (Week 103)
Change From Baseline in Normalized Spleen Volume at Week 51 and EOS (Week 103)
Time Frame: Baseline, Week 51 and EOS (Week 103)
Normalized spleen volume was measured by MRI. Spleen volume was normalized for % of body weight. Spleen size relative to body weight= (Spleen volume [cc]/Body weight [kg])*100. Baseline was defined as last data collected prior to the first administration of study drug. Change from baseline in normalized spleen volume at Week 51 and EOS (Week 103) was reported.
Baseline, Week 51 and EOS (Week 103)
Change From Baseline in Severity of Bone Pain at Week 51 and EOS (Week 103)
Time Frame: Baseline, Week 51 and EOS (Week 103)
Bone pain was measured by questions taken from the Brief Pain Inventory-short form (BPI-SF). Pain severity was evaluated based on the average of 4 questions from BPI-SF (Questions 3 through 6) assessing worst pain, least pain, average pain, and pain right now, each rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine) with mild pain- score (1 to 4), moderate pain- score (5 to 6), and severe pain score (7 to 10). Overall severity score was calculated as average of 4 questions ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A negative change from baseline score indicates improvement. Baseline was defined as last data collected prior to the first administration of study drug. Change from baseline in severity of bone pain at Week 51 and EOS (Week 103) was reported.
Baseline, Week 51 and EOS (Week 103)
Change From Baseline in Bone Pain Interference Score at Week 51 and EOS (Week 103)
Time Frame: Baseline, Week 51 and EOS (Week 103)
Bone pain interference was measured by questions taken from the BPI-SF. Pain interference was evaluated based upon average of 7 questions from BPI-SF (9A through 9G) regarding the extent to which pain interfered with daily activities, including general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life in the last 24 hours, each rated on a scale from 0 (does not interfere) to 10 (completely interferes). Overall pain interference score was calculated as average of 7 questions ranging from 0 (does not interfere) to 10 (completely interferes). A negative change from baseline score indicates improvement. Baseline was defined as last data collected prior to the first administration of study drug. Change from baseline in bone pain interference score at Week 51 and EOS (Week 103) was reported.
Baseline, Week 51 and EOS (Week 103)
Change From Baseline in Overall Fatigue Measured by Brief Fatigue Inventory (BFI) at Week 51 and EOS (Week 103)
Time Frame: Baseline, Week 51 and EOS (Week 103)
Overall fatigue was measured by the BFI. BFI was a 9-item questionnaire developed to assess subjective fatigue. Each question asked the respondent to rate the level of their experienced fatigue over the past 24 hours on an 11-point (0-10) scale. First 3 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". Next 6 questions assessed the level fatigue interference with daily activities included 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="no interference" while a score of 10="complete interference. Overall fatigue score was calculated as average score of all 9 items on the BFI ranging from 0="no fatigue" to 10="as bad as you can imagine".
Baseline, Week 51 and EOS (Week 103)
Number of Participants With Shift in World Health Organization (WHO) BMD Classifications Based on LS T-Scores at Week 51 and EOS (Week 103)
Time Frame: Baseline, Week 51 and EOS (Week 103)
WHO BMD Classifications (Normal Bone Density, Osteopenia, Osteoporosis), bone mineral density was classified based on LS BMD T-scores. BMD T-score was a comparison of an individual's BMD compared to "normal". Also, BMD T-score is the standard deviation of the difference between measured BMD and that of the healthy young adult "normal". The T-score scale was as follows: -1 and above=normal, -1 to -2.5=osteopenia (below normal and may lead to osteoporosis), and -2.5 and below=osteoporosis. Number of participants with shift in WHO BMD classifications based on LS T-Scores at Week 51 and EOS (Week 103) were reported.
Baseline, Week 51 and EOS (Week 103)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From start of study drug infusion up to follow-up (107 weeks)
An adverse event (AE) was 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. A TEAE was defined as any AE that occurred on or after the time of the first infusion of study drug until 30 days after the last infusion of study drug. Number of participants with TEAEs were reported.
From start of study drug infusion up to follow-up (107 weeks)
Number of Participants Who Developed Positive Anti-velaglucerase Alfa Antibody Status
Time Frame: Baseline up to EOS (Week 103)
Anti-velaglucerase alfa antibody included anti-velaglucerase antibodies (ADA) and neutralizing anti-velaglucerase antibodies (NAb). The Anti-velaglucerase antibody status was summarized as categorical variable by positive and negative. Number of participants who developed positive anti-velaglucerase alfa antibody were reported.
Baseline up to EOS (Week 103)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shire

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 29, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 12, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 9, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 1, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 3, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SHP-GCB-402
  • 2015-001578-17 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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