Long Term Impact of Rapid Intravenous Infusion of Velaglucerase Alfa (VPRIV)
Primary Purpose
Gaucher Disease, Type 1
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
VPRIV
Sponsored by
About this trial
This is an interventional treatment trial for Gaucher Disease, Type 1
Eligibility Criteria
Inclusion Criteria:
- Aged 18-75 years, non-splenectomized Enzymatic diagnosis & molecular analysis indicative of type 1 Gaucher disease Receiving VPRIV for at least 6 infusions (3 months) prior to Baseline at a constant dose and frequency and without clinically significant AEs including allergic reactions
Exclusion Criteria:
- Experience of a clinically significant AE to VPRIV at any time in the past Existence of a clinically significant co-morbidity
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rapid infusion of Vpriv
Arm Description
: Infusions at Baseline and during step-wise rate increases and End-of-study will be performed in the Shaare Zedek Medical Center (SZMC) by the Study Nurse who will monitor vital signs (see below) for a total of 8 visits at SZMC. Home therapy will be approved if the patient so desires for 5 infusions in Phase 1 and for the first 5 infusions in Phase 3. All routine hematological and biochemical tests will be performed in the SZMC clinical labs. Abdominal quantitative MR Imaging (MRI) for spleen and liver volumes will be performed at SZMC
Outcomes
Primary Outcome Measures
Incidence of change from baseline in blood pressure for rapid infusion-1
measured by blood pressure pre and post infusion
Incidence of change from baseline in heart rate for rapid infusion-1
measured by heart rate pre and post infusion
Incidence of change from baseline in temperature for rapid infusion-1
measured by temperature pre and post infusion
Secondary Outcome Measures
Non deterioration in Gaucher manifestations- stability in platelet counts
Efficacy secondary endpoints are non-deterioration (defined as stability) in platelet count
Non deterioration in Gaucher manifestations- stability in hemaglobin count
Efficacy secondary endpoints are non-deterioration (defined as stability) in hemaglobin count
Non deterioration in Gaucher manifestations- measured by liver volume
Efficacy secondary endpoints are non-deterioration (defined as stability) in organ volumes of liver volume (as previously defined in the TKT034 clinical trial)
Non deterioration in Gaucher manifestations- measured by spleen volumes
Efficacy secondary endpoints are non-deterioration (defined as stability) in organ volumes of spleen volume (as previously defined in the TKT034 clinical trial)
Non deterioration in Gaucher manifestations- measured by lack of elevated biomarker- Lyso-GB1
Efficacy secondary endpoints are non-deterioration (defined as stability) by lack of sustained increases in the biomarkers.
Full Information
NCT ID
NCT04120506
First Posted
August 10, 2018
Last Updated
October 27, 2022
Sponsor
Shaare Zedek Medical Center
Collaborators
Shire
1. Study Identification
Unique Protocol Identification Number
NCT04120506
Brief Title
Long Term Impact of Rapid Intravenous Infusion of Velaglucerase Alfa (VPRIV)
Official Title
Long Term Impact of Rapid Intravenous Infusion of Velaglucerase Alfa (VPRIV) in Adult Patients With Type 1 Gaucher Disease, Previously on a Stable Dose of VPRIV for at Least 3 Months: an Extension of the Investigator-initiated Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
January 10, 2016 (Actual)
Primary Completion Date
January 20, 2017 (Actual)
Study Completion Date
January 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shaare Zedek Medical Center
Collaborators
Shire
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Background: In order to allow our satisfied patients, who have successfully completed 24 months of rapid intravenous infusion of Velaglucerase alfa (VPRIV), to continue with the 10 minutes IV therapy, the clinical trial framework must be extended; and this extension is important for the assessment of long term benefit (up to 5 years) of this regimen of administration of Velaglucerase alfa..
Suggested trial: An additional 36 months home therapy follow up of safety and efficacy of rapid intravenous infusion of Velaglucerase alfa (VPRIV) in adult patients with type 1 Gaucher disease.
Patients must have completed the prior 4 parts / 24 months of the protocol before enrolling into this extension phase ("Part 5") and have provided a new consent before entering PART 5 of the study.
Patients must not have experienced clinically significant AEs, including allergic reactions, in any of the prior study parts of this protocol to be eligible to participate, and have maintained stability in the key disease features.
All infusions of 10' will be given in the context of home therapy. "Clinically significant" AEs will be determined by the PI using standard description of AEs as previously described at phase 3, and if necessary will support withdrawal of the patient from the study.
Detailed Description
Every 6 months, patients will be required to come for routine checkups at SZMC, where the following tests will be performed:
Complete Blood Count (CBC)
Routine serum biochemistry including liver function tests (LFTs)
Plasma biomarker lyso Gb-1
Height & weight & calculation of BMI
Physical examination and medical history elicited including concomitant medications
Ultrasound for spleen and liver volumes
In addition, the following tests will be performed at 12, 24 and 36 months:
Echocardiography
Electrocardiogram (ECG)
Urinalysis
HRQoL questionnaire (TBD)
At each home visit, the following assessments will be performed by the study nurse:
Queries regarding AEs and changes in clinically relevant Gaucher parameters as described by the patient (e.g., bone pain), inter-current illnesses, etc.
Patients will be required to complete the End-of-study visit, including the final infusion at 10', at SZMC. This final visit will include in addition to the usual safety and efficacy assessments and routine tests, (mentioned above) also, DEXA and anti-drug antibodies.
In addition, we would perform a 4th PK measurement at end of the extension period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gaucher Disease, Type 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
Objective: To show non-inferiority of rapid (defined as 10') intravenous (IV) infusion versus standard IV infusion rate (60') of VPRIV with regard to safety, pharmacokinetic(PK) profile, and efficacy in patients who have been receiving VPRIV for a minimum of 3 months at a constant dosage.
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rapid infusion of Vpriv
Arm Type
Experimental
Arm Description
: Infusions at Baseline and during step-wise rate increases and End-of-study will be performed in the Shaare Zedek Medical Center (SZMC) by the Study Nurse who will monitor vital signs (see below) for a total of 8 visits at SZMC. Home therapy will be approved if the patient so desires for 5 infusions in Phase 1 and for the first 5 infusions in Phase 3. All routine hematological and biochemical tests will be performed in the SZMC clinical labs. Abdominal quantitative MR Imaging (MRI) for spleen and liver volumes will be performed at SZMC
Intervention Type
Drug
Intervention Name(s)
VPRIV
Other Intervention Name(s)
Velaglucerase Alfa
Intervention Description
Safety, pharmacokinetics, and efficacy of rapid intravenous infusion of velaglucerase alfa (VPRIV) in adult patients with type 1 Gaucher disease
Primary Outcome Measure Information:
Title
Incidence of change from baseline in blood pressure for rapid infusion-1
Description
measured by blood pressure pre and post infusion
Time Frame
9 months
Title
Incidence of change from baseline in heart rate for rapid infusion-1
Description
measured by heart rate pre and post infusion
Time Frame
9 months
Title
Incidence of change from baseline in temperature for rapid infusion-1
Description
measured by temperature pre and post infusion
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Non deterioration in Gaucher manifestations- stability in platelet counts
Description
Efficacy secondary endpoints are non-deterioration (defined as stability) in platelet count
Time Frame
9 months
Title
Non deterioration in Gaucher manifestations- stability in hemaglobin count
Description
Efficacy secondary endpoints are non-deterioration (defined as stability) in hemaglobin count
Time Frame
9 months
Title
Non deterioration in Gaucher manifestations- measured by liver volume
Description
Efficacy secondary endpoints are non-deterioration (defined as stability) in organ volumes of liver volume (as previously defined in the TKT034 clinical trial)
Time Frame
9 months
Title
Non deterioration in Gaucher manifestations- measured by spleen volumes
Description
Efficacy secondary endpoints are non-deterioration (defined as stability) in organ volumes of spleen volume (as previously defined in the TKT034 clinical trial)
Time Frame
9 months
Title
Non deterioration in Gaucher manifestations- measured by lack of elevated biomarker- Lyso-GB1
Description
Efficacy secondary endpoints are non-deterioration (defined as stability) by lack of sustained increases in the biomarkers.
Time Frame
9 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged 18-75 years, non-splenectomized Enzymatic diagnosis & molecular analysis indicative of type 1 Gaucher disease Receiving VPRIV for at least 6 infusions (3 months) prior to Baseline at a constant dose and frequency and without clinically significant AEs including allergic reactions
Exclusion Criteria:
Experience of a clinically significant AE to VPRIV at any time in the past Existence of a clinically significant co-morbidity
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ari Zimran
Organizational Affiliation
Ari Zimran - Shaare Zedek
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29989200
Citation
Zimran A, Revel-Vilk S, Becker-Cohen M, Chicco G, Arbel N, Rolfs A, Szer J. Rapid intravenous infusion of velaglucerase-alfa in adults with type 1 Gaucher disease. Am J Hematol. 2018 Sep;93(9):E246-E248. doi: 10.1002/ajh.25205. Epub 2018 Aug 9. No abstract available.
Results Reference
result
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Long Term Impact of Rapid Intravenous Infusion of Velaglucerase Alfa (VPRIV)
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