ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01842841
Recruitment Status : Completed
First Posted : April 30, 2013
Results First Posted : December 14, 2015
Last Update Posted : December 14, 2015
Sponsor:
Collaborator:
Quintiles, Inc.
Information provided by (Responsible Party):
Shire

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Gaucher Disease Drug: velaglucerase alfa Phase 3

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  (Clinical Trial)
Actual Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label Extension Study of Velaglucerase Alfa Enzyme Replacement Therapy in Japanese Patients With Gaucher Disease
Study Start Date : March 2013
Actual Primary Completion Date : October 2014
Actual Study Completion Date : October 2014


Arm Intervention/treatment
Experimental: velaglucerase alfa
15 to 60 U/kg, EOW via intravenous infusion
Drug: velaglucerase alfa
15-60 U/kg, EOW
Other Name: VPRIV




Primary Outcome Measures :
  1. Number of Participants With Drug-related Adverse Events (AEs), Infusion-related AEs, and Serious AEs (SAEs) [ Time Frame: From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks) ]
    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.

  2. Number of Participants Using Concomitant Medication [ Time Frame: From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks) ]
  3. Number of Participants With Abnormal and Clinically Significant Laboratory Test Results [ Time Frame: From Week 65 until the end of study (Week 155) ]
    Laboratory test results were considered abnormal and clinically significant at the discretion of the investigator.

  4. Number of Participants With Positive Anti-Velaglucerase Alfa Antibodies [ Time Frame: From Week 65 until the end of study (Week 155) ]
    Serum samples were collected for all participants for determination of anti-velaglucerase alfa antibodies every 12 weeks.


Secondary Outcome Measures :
  1. Change From Baseline in Hemoglobin Concentration at Week 101 [ Time Frame: Baseline, 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).

  2. Change From Baseline in Platelet Count at Week 101 [ Time Frame: Baseline, 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).

  3. Change From Baseline in Liver Volume Normalized to Body Weight at Week 103 [ Time Frame: Baseline, 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.

  4. Change From Baseline in Spleen Volume Normalized to Body Weight at Week 103 [ Time Frame: Baseline, 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.

  5. Change From Baseline in Bone Mineral Density (BMD) at Week 103: Z Score [ Time Frame: Baseline, Week 103 ]
    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.

  6. Change From Baseline in Bone Mineral Density (BMD) at Week 103: T-Score [ Time Frame: Baseline, Week 103 ]
    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.

  7. Change From Baseline in Bone Marrow Burden (BMB) Score at Week 103 [ Time Frame: Baseline, 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.

  8. Change From Baseline in Growth Velocity at Week 101 : Height Z-Score [ Time Frame: Baseline, Week 101 ]
    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.

  9. Change From Baseline in Skeletal Age at Week 103: Z-Score [ Time Frame: Baseline, Week 103 ]
    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.

  10. Change From Baseline in Plasma Chitotriosidase Levels at Week 101 [ Time Frame: Baseline, 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.

  11. Number of Participants With Change From Baseline in Neurological Status at Week 103 [ Time Frame: Baseline, 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.

  12. Change From Baseline in Chemokine [C-C Motif] Ligand 18 (CCL18) Levels at Week 101 [ Time Frame: Baseline, 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01842841


Locations
Japan
Hamamatsu University School of Medicine
Hamamatsu, Shizuoka, Japan, 431-3192
Iwata City Hospital
Okubo, Shizuoka, Japan, 438-8550
The Jikei University School of Medicine
Minato-ku, Tokyo, Japan, 105-8471
Chiba Children's Hospital
Chiba, Japan, 266-0007
Osaka City University Hospital
Osaka, Japan, 545-8586
Sponsors and Collaborators
Shire
Quintiles, Inc.
Investigators
Study Director: Björn Mellgard, MD Shire

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01842841     History of Changes
Other Study ID Numbers: HGT-GCB-091
First Posted: April 30, 2013    Key Record Dates
Results First Posted: December 14, 2015
Last Update Posted: December 14, 2015
Last Verified: September 2015

Additional relevant MeSH terms:
Gaucher Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Sphingolipidoses
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors