Multicenter Extension Study of Velaglucerase Alfa in Japanese Patients With Gaucher Disease

A Multicenter, Open-label Extension Study of Velaglucerase Alfa Enzyme Replacement Therapy in Japanese Patients With Gaucher Disease

Gaucher disease is an inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCB) that leads to progressive accumulation of glucocerebroside within macrophages and subsequent tissue and organ damage; typically of the liver, spleen, bone marrow, and brain. Type 1 Gaucher disease affects an estimated 30,000 persons worldwide and is the most common. Type 1 Gaucher disease does not involve the central nervous system. Patients with Type 2 Gaucher disease present with acute neurological deterioration, which leads to early death. Those with Type 3 disease typically display a more sub-acute neurological course, with later onset and slower progression.

The primary objective of this study is to evaluate the long-term safety of every other week (EOW) dosing of velaglucerase alfa in Japanese patients with Gaucher disease who completed study HGT-GCB-087 and elected to continue treatment with velaglucerase alfa.

Velaglucerase alfa has been developed and approved as an enzyme replacement therapy for Type 1 Gaucher disease.

Study Overview

• Status: Completed
• Conditions: Gaucher Disease
• Intervention / Treatment: Drug: velaglucerase alfa

Detailed Description

Gaucher disease is an inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCB) that leads to progressive accumulation of glucocerebroside within macrophages and subsequent tissue and organ damage; typically of the liver, spleen, bone marrow, and brain.

Gaucher disease has been designated in the list of Specified Rare and Intractable Diseases by Specified Disease Treatment Research Program of Ministry of Health, Labor and Welfare (MHLW) as one of "lysosomal storage diseases" since 2001. Gaucher disease is also designated in the Medical Aid Program for Specified Categories of Chronic Pediatric Diseases.

The prevalence of mutations and the phenotype of patients with Gaucher disease in Japan differs from that in non-Japanese populations. Some patients with type 1 Gaucher disease in Japan have more severe and progressive disease compared to non-Japanese patients and the disease is characterized by an earlier onset of symptoms.

Velaglucerase alfa, a highly-purified form of the naturally occurring enzyme glucocerebrosidase, has been developed as an enzyme replacement therapy for Gaucher disease for the symptoms (anemia, thrombocytopenia, hepatomegaly, splenomegaly, and bone manifestation).

The primary objective of this study is to evaluate the long-term safety of every other week (EOW) dosing of velaglucerase alfa in Japanese patients with Gaucher disease who completed study HGT-GCB-087 and elected to continue treatment with velaglucerase alfa.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 266-0007
    • Chiba Children's Hospital
  • Osaka, Japan, 545-8586
    • Osaka City University Hospital
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 431-3192
      • Hamamatsu University School of Medicine
    • Okubo, Shizuoka, Japan, 438-8550
      • Iwata City Hospital
  • Tokyo
    • Minato-ku, Tokyo, Japan, 105-8471
      • The Jikei University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient has completed treatment with EOW velaglucerase alfa through Week 51 of study HGT-GCB-087.
• Female patients of child bearing potential must agree to use a medically acceptable method of contraception at all times during the study.
• The patient, the patient's parent(s)or legal guardian(s) has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee(IRB/IEC)
• The patient must be sufficiently cooperative to participate in this clinical study as judged by the Investigator.

Exclusion Criteria:

• The patient has received treatment with any investigational drug, other than velaglucerase alfa, or investigational device within 30 days prior to study entry; such use during the study is not permitted.
• The patient, patient's parent(s), or patient's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study.
• The patient has a significant comorbidity, as determined by the Investigator that might affect study data or confound the study results.
• The patient is unable to comply with the protocol as determined by the Investigator.

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: velaglucerase alfa; 15 to 60 U/kg, EOW via intravenous infusion	Drug: velaglucerase alfa; 15-60 U/kg, EOW; Other Names: VPRIV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Drug-related Adverse Events (AEs), Infusion-related AEs, and Serious AEs (SAEs)	An AE was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered related to investigational product. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An infusion-related AE was defined as an AE that started either during or within 12 hours after the start of the infusion and that was judged as possibly or probably related to investigational product.	From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
Number of Participants Using Concomitant Medication		From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
Number of Participants With Abnormal and Clinically Significant Laboratory Test Results	Laboratory test results were considered abnormal and clinically significant at the discretion of the investigator.	From Week 65 until the end of study (Week 155)
Number of Participants With Positive Anti-Velaglucerase Alfa Antibodies	Serum samples were collected for all participants for determination of anti-velaglucerase alfa antibodies every 12 weeks.	From Week 65 until the end of study (Week 155)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin Concentration at Week 101	Baseline was the modified baseline hemoglobin concentration, the average of the values from screening, baseline, and Week 1 Day 1 from Study HGT-GCB-087 (NCT01614574).	Baseline, Week 101
Change From Baseline in Platelet Count at Week 101	Baseline was the modified baseline platelet count, the average of the values from screening, baseline, and Week 1 Day 1 from Study HGT-GCB-087 (NCT01614574).	Baseline, Week 101
Change From Baseline in Liver Volume Normalized to Body Weight at Week 103	Liver volume was measured using magnetic resonance imaging (MRI). Liver volume measurements were normalized to the percentage of body weight. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.	Baseline, Week 103
Change From Baseline in Spleen Volume Normalized to Body Weight at Week 103	Spleen volume was measured using MRI. Spleen volume measurements were normalized to the percentage of body weight. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.	Baseline, Week 103
Change From Baseline in Bone Mineral Density (BMD) at Week 103: Z Score	BMD was measured by dual energy x-ray absorptiometry (DXA) for lumbar spine and femurs. To ensure standardization and allow for comparisons of BMD, results were converted to standardized Z-scores (matched for age and gender). Z-scores express the BMD as the number of standard deviations (SDs) above or below the average BMD of a healthy participant of the same age and gender. Statistical analysis plan only required summarization if greater than (>) 50 percent (%) of participants had evaluable data. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.	Baseline, Week 103
Change From Baseline in Bone Mineral Density (BMD) at Week 103: T-Score	BMD was measured by DXA for lumbar spine and femurs. To ensure standardization and allow for comparisons of BMD, results were converted to standardized T-scores; normal values were used from databases from Hologic based on standard criteria. T-scores are the number of SDs above or below the average for a young adult at peak BMD. Statistical analysis plan only required summarization if >50% of participants had evaluable data. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.	Baseline, Week 103
Change From Baseline in Bone Marrow Burden (BMB) Score at Week 103	BMB Score was measured using 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 score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0-16 points. A higher BMB score signified more severe bone marrow involvement. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.	Baseline, Week 103
Change From Baseline in Growth Velocity at Week 101 : Height Z-Score	The Z-score, or Standard Deviation Score, is a measure of number of SDs above or below the average BMD of a healthy participant of the same age and gender. World Health Organization 2007 growth reference data were used for Z-score calculation. Statistical analysis plan only required summarization if >50% of participants had evaluable data. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.	Baseline, Week 101
Change From Baseline in Skeletal Age at Week 103: Z-Score	Skeletal age was measured via radiography (X-ray) of the left hand and wrist by the method of Greulich and Pyle. The Z-score, or Standard Deviation Score, is a measure of number of SDs above or below the average BMD of a healthy participant of the same age and gender. Statistical analysis plan only required summarization if >50% of participants had evaluable data. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.	Baseline, Week 103
Change From Baseline in Plasma Chitotriosidase Levels at Week 101	Plasma chitotriosidase activity levels were measured using an enzymatic assay with 4-methylumbelliferyl-deoxychitobiose as a substrate. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.	Baseline, Week 101
Number of Participants With Change From Baseline in Neurological Status at Week 103	Neurological status was considered normal or abnormal based on investigator's discretion. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.	Baseline, Week 103
Change From Baseline in Chemokine [C-C Motif] Ligand 18 (CCL18) Levels at Week 101	Plasma CCL18 concentrations were measured using a time-resolved fluorescence assay. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.	Baseline, Week 101

Collaborators and Investigators

• Sponsor: Shire
• Collaborators: Quintiles, Inc.

Publications and helpful links

General Publications

• Ida H, Tanaka A, Matsubayashi T, Murayama K, Hongo T, Lee HM, Mellgard B. A multicenter, open-label extension study of velaglucerase alfa in Japanese patients with Gaucher disease: Results after a cumulative treatment period of 24months. Blood Cells Mol Dis. 2016 Jul;59:140-7. doi: 10.1016/j.bcmd.2015.10.002. Epub 2015 Oct 16.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2013
• Primary Completion (Actual): October 8, 2014
• Study Completion (Actual): October 8, 2014

Study Registration Dates

• First Submitted: April 11, 2013
• First Submitted That Met QC Criteria: April 25, 2013
• First Posted (Estimate): April 30, 2013

Study Record Updates

• Last Update Posted (Actual): June 14, 2021
• Last Update Submitted That Met QC Criteria: May 18, 2021
• Last Verified: May 1, 2021

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: HGT-GCB-091