Long Term Impact of Rapid Intravenous Infusion of Velaglucerase Alfa (VPRIV)

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

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.

Study Overview

• Status: Completed
• Conditions: Gaucher Disease, Type 1
• Intervention / Treatment: Drug: VPRIV

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Rapid infusion of Vpriv; : 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

Drug: VPRIV; Safety, pharmacokinetics, and efficacy of rapid intravenous infusion of velaglucerase alfa (VPRIV) in adult patients with type 1 Gaucher disease; Other Names: Velaglucerase Alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of change from baseline in blood pressure for rapid infusion-1	measured by blood pressure pre and post infusion	9 months
Incidence of change from baseline in heart rate for rapid infusion-1	measured by heart rate pre and post infusion	9 months
Incidence of change from baseline in temperature for rapid infusion-1	measured by temperature pre and post infusion	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non deterioration in Gaucher manifestations- stability in platelet counts	Efficacy secondary endpoints are non-deterioration (defined as stability) in platelet count	9 months
Non deterioration in Gaucher manifestations- stability in hemaglobin count	Efficacy secondary endpoints are non-deterioration (defined as stability) in hemaglobin count	9 months
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)	9 months
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)	9 months
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.	9 months

Collaborators and Investigators

• Sponsor: Shaare Zedek Medical Center
• Collaborators: Shire

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2016
• Primary Completion (Actual): January 20, 2017
• Study Completion (Actual): January 1, 2022

Study Registration Dates

• First Submitted: August 10, 2018
• First Submitted That Met QC Criteria: October 7, 2019
• First Posted (Actual): October 9, 2019

Study Record Updates

• Last Update Posted (Actual): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Gaucher Disease
• Other Study ID Numbers: 0075-15-SZMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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