Assessing the Impact of Elelyso on Bone Involvement Currently Treated With Other ERTs

An Open-label, Investigator Initiated Clinical Trial to Asses Impact of Elelyso on Bone Involvement in Patients With Gaucher Disease Currently Treated With Other ERTs

The objective of this study is to assess Elelyso treatment on bone disease in Gaucher patients currently treated with other enzyme replacement therapy.

Experience from early access program (2009-2012) has suggested that some patients who have been stable on imiglucerase have shown poor scores of QCSI with Fat Fraction below the cut off point of 0.23 which is considered "bone at risk", and have demonstrated remarkable improvement upon switching to Elelyso, including particularly 2 patients who did not have any change in dose or any drug interruption prior to the switch.

These findings may be explained by the better glycan structure of imiglucerase (see Tekoah et al, 2013). The fact that in many patients prevention of bony complications is the main indication for ERT highlights the importance of this study, as all clinical trials of all ERTS heretofore did not include the bones as primary or secondary end-points but only as exploratory, and as such had only limited value,

Study Overview

• Status: Completed
• Conditions: Gaucher Disease, Type 1
• Intervention / Treatment: Procedure: quantitative chemical shift imaging (QCSI); Drug: Elelyso

Detailed Description

Open-label study in patients with Gaucher disease currently treated with commercial ERTs. Eligible patients will receive intravenous (IV) infusions of Elelyso every two weeks. The infusions will be administered at the selected medical center or in the home care setup. The dose of Elelyso will be the same dose of the other ERTs . Bone parameters QCSI and BMD will be assessed at baseline, 12 months and 24 months.

The intention is to open 3 more sites in Israel thereby making this IIR a multi center national trial

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• GD patients, male and female, 18 years or older
• Currently treated with enzyme replacement therapy for 5 years and more, with a stable unchanged dose in the previous 6 months
• Imaging features of significant residual bone disease defined as QCSI under 0.3 bone at risk
• Able to provide written informed consent

Exclusion Criteria:

• Currently taking another experimental drug for any condition
• Presence of any medical, emotional, behavioral or psychological condition that in the judgment of the Investigator would interfere with the patient's compliance with the requirements of the study.
• Past exposure to Elelyso

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Trial to asses impact of Elelyso on bone involvement in patien; The infusions will be administered at the selected medical center or in the home care setup. The dose of intravenous (IV) infusions of Elelyso will be the same dose of the other ERTs . Bone parameters QCSI and BMD will be assessed at baseline, 12 months and 24 months.	Procedure: quantitative chemical shift imaging (QCSI); Poor scores of QCSI with Fat Fraction below the cut off point of 0.3 which is considered "bone at risk"; Drug: Elelyso; intravenous (IV) infusions of Elelyso; Other Names: Taliglucerase Alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QCSI results at 12 months, Fat fraction under 0.3.	Improvement of QCSI results in patients with Gaucher disease currently treated with commercial ERTs. Eligible patients will receive intravenous (IV) infusions of Elelyso every two weeks. The infusions will be administered at the selected medical center or in the home care setup. The dose of Elelyso will be the same dose of the other ERTs . Bone parameters QCSI and BMD will be assessed at 12 months.	12 months
QCSI results at 24 months, Fat fraction under 0.3.	Improvement of QCSI results in patients with Gaucher disease currently treated with commercial ERTs. Eligible patients will receive intravenous (IV) infusions of Elelyso every two weeks. The infusions will be administered at the selected medical center or in the home care setup. The dose of Elelyso will be the same dose of the other ERTs . Bone parameters QCSI and BMD will be assessed at 24 months.	24 months

Collaborators and Investigators

• Sponsor: Shaare Zedek Medical Center
• Collaborators: Pfizer
• Investigators: Principal Investigator: Ari Zimran, MD, Shaheed Ziaur Rahman Medical College

Publications and helpful links

General Publications

• van Dussen L, Zimran A, Akkerman EM, Aerts JM, Petakov M, Elstein D, Rosenbaum H, Aviezer D, Brill-Almon E, Chertkoff R, Maas M, Hollak CE. Taliglucerase alfa leads to favorable bone marrow responses in patients with type I Gaucher disease. Blood Cells Mol Dis. 2013 Mar;50(3):206-11. doi: 10.1016/j.bcmd.2012.11.001. Epub 2012 Nov 28.
• Zimran A, Dinur T, Revel-Vilk S, Akkerman EM, van Dussen L, Hollak CEM, Maayan H, Altarescu G, Chertkoff R, Maas M. Improvement in bone marrow infiltration in patients with type I Gaucher disease treated with taliglucerase alfa. J Inherit Metab Dis. 2018 Nov;41(6):1259-1265. doi: 10.1007/s10545-018-0195-y. Epub 2018 Jul 31.
• van Dussen L, Akkerman EM, Hollak CE, Nederveen AJ, Maas M. Evaluation of an imaging biomarker, Dixon quantitative chemical shift imaging, in Gaucher disease: lessons learned. J Inherit Metab Dis. 2014 Nov;37(6):1003-11. doi: 10.1007/s10545-014-9726-3. Epub 2014 Jun 13.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2017
• Primary Completion (ACTUAL): July 31, 2021
• Study Completion (ACTUAL): July 31, 2021

Study Registration Dates

• First Submitted: April 13, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (ACTUAL): April 20, 2020

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: 138-16-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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No