A Multicenter, Safety and Efficacy Study of Taliglucerase Alfa in Subjects With Type 3 Gaucher Disease

• ClinicalTrials.gov Identifier: NCT04002830
• Recruitment Status: Completed
• First Posted: July 1, 2019
• Last Update Posted: November 24, 2023
• Sponsor: Ari Zimran
• Collaborator: Pfizer
• Information provided by (Responsible Party): Ari Zimran, Shaare Zedek Medical Center

Study Description

Brief Summary:

This is a multicenter study to assess the safety and efficacy of taliglucerase alfa (60 units/kg) in previously untreated subjects of any age with Type 3 GD. Subjects will receive an infusion of taliglucerase alfa every 2 weeks for 12 months. Subjects who tolerate the infusions well, and who are treated in centers where home therapy is the SOC will be allowed to switch from site to home treatment at the discretion of the PI but after no less than 3 uneventful infusions at the site.

Condition or disease	Intervention/treatment	Phase
Gaucher Disease, Type 3	Drug: Elelyso	Phase 4

Detailed Description:

Patients with Type 3 GD exhibit both visceral and neurologic manifestations. In addition to the progressive neurologic involvement, somatic disease manifestations, especially splenomegaly and resulting cytopenia, contribute to significant mortality and morbidity . The effects of enzyme replacement therapy (ERT) on patients with Type 1 GD have been clearly documented and have a beneficial effect on visceral and hematologic disease parameters . It is known that recombinant enzyme does not pass the blood-brain barrier and has no effect on neurologic involvement . Probably due to the rarity of Type 3 GD, information on the somatic effects of ERT is largely limited to case reports or single-center series. There are also few reviews of cohorts but the clinical subtype, age, genotype, ERT dosage, accompanying therapies, and treatment response vary widely among patients in these cohorts. This prospective study aims to objectively evaluate the hematologic and visceral effects of ERT with taliglucerase alfa on a rather clinically and genetically homogenous group of treatment-naïve patients with Type 3 GD . For the purposes of this study, subjects receiving no Gaucher-specific medications for at least 12 months will be considered "untreated". The results of this study are expected to provide a more objective view of the degree of response of this patient type, and potentially create new areas of research.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Type 3 Gaucher disease patients
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Safety and Efficacy Study of Taliglucerase Alfa in Subjects With Type 3 Gaucher Disease
• Actual Study Start Date: November 20, 2020
• Actual Primary Completion Date: July 30, 2023
• Actual Study Completion Date: July 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Taliglucerase Alpha; Intravenous infusion of Taligluucerase alfa (Elelyso) in treatment-naive patients with type 3 Gaucher disease	Drug: Elelyso; Taliglucerase alfa is currently an approved therapy in the United States and many other countries for adults and children with a confirmed diagnosis of Type 1 GD ,and is also approved for use in Type 3 GD in a small number of countries.; Other Name: Taliglucerase Alfa

Outcome Measures

Primary Outcome Measures :

1. Percent change from baseline in spleen volume measured by MRI [ Time Frame: from baseline to month 12 ]
   Percent change from baseline

Secondary Outcome Measures :

1. Percent change from baseline in liver volume measured by MRI [ Time Frame: from baseline to month 12 ]
   Percent change from baseline
2. Percent change in hemoglobin [ Time Frame: from baseline to Months 3, 6, 9, and 12 ]
   Percent change from baseline
3. Percent change in platelet count [ Time Frame: from baseline to Months 3, 6, 9, and 12 ]
   Percent change from baseline
4. Percent change in Lyso-GB1 [ Time Frame: from baseline to Months 3, 6, 9, and 12 ]
   Percent change from baseline

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female of any age; however, if female:

   • must be using contraception if of childbearing potential or must be surgically sterile
   • must not be lactating
2. Diagnosis of Type 3 GD by enzyme and sequence analysis; and confirmed by the Medical Monitor.
3. Splenomegaly at least 5 x multiples of normal (MN).
4. Treatment-naïve.

Exclusion Criteria:

Eligible subjects may not have any of the following exclusion criteria:

1. Type 2 GD.
2. Presence of myoclonic seizures.

3. At least one allele of:

   • N370S (N409S in recent nomenclature)
   • R496H (R535H in recent nomenclature)
4. Presence of calcification in heart valves or arteries in echocardiography.
5. Presence of untreated iron, folic acid, vitamin B12 deficiency and/or hypothyroidism. (Resolved anemia is not an exclusion criterion.)
6. Presence of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and/or hepatitis C infections.
7. Splenectomy and bone marrow transplantation.
8. Presence of any medical, emotional, behavioural, or psychological condition that in the judgment of the Investigator would interfere with the subject's compliance with the requirements of the study.
9. Any other disorder that may interfere with the results of the efficacy endpoints.
10. Pregnancy or breastfeeding.
11. Currently taking another investigational drug for any condition or any therapeutic drug for Gaucher disease.
12. The subject and/or subject's parent(s) or legal guardian(s) are unable to understand the nature, scope, and possible consequences of the study.
13. Medical history of any food/drugs allergy.

Contacts and Locations

Locations

India

All India Institute of Medical Sciences

New Delhi, India

Israel

Shaare Zedek Medical Center

Jerusalem, Israel, 9103102

Turkey

Gazi University

Ankara, Turkey

Sponsors and Collaborators

Ari Zimran

Pfizer

Investigators

• Principal Investigator: Ari Zimran, Prof.; Shaare Zedek Medical Center

More Information

• Responsible Party: Ari Zimran, PI, Shaare Zedek Medical Center
• ClinicalTrials.gov Identifier: NCT04002830
• Other Study ID Numbers: WI224302
• First Posted: July 1, 2019
• Last Update Posted: November 24, 2023
• Last Verified: November 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Gaucher Disease; 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; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders