Study of Velaglucerase Alfa Enzyme Replacement Therapy in Japanese Patients With Gaucher Disease

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01614574
• Collaborator: (none)
• Enrollment: 6
• Locations: 3
• Arm: 1
• Actual Duration (Months): 14.8
• Patients Per Site: 2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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. The disease has been classified into 3 clinical subtypes based on the presence or absence of neurological symptoms and severity of neurological disease. 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 safety of every other week dosing of velaglucerase alfa in Japanese patients with Gaucher disease.

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	Biological: 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 safety of every other week dosing of velaglucerase alfa in Japanese patients (naive or previously treated with imiglucerase) 2 years of age and older with Gaucher disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-Label Study of Velaglucerase Alfa Enzyme Replacement Therapy in Japanese Patients With Gaucher Disease
• Actual Study Start Date: Mar 2, 2012
• Actual Primary Completion Date: May 25, 2013
• Actual Study Completion Date: May 25, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Investigational velaglucerase alfa	Biological: velaglucerase alfa; 60 U/kg every other week intravenous infusion; Other Names: VPRIV Gene activated human glucocerebrosidase

Outcome Measures

Primary Outcome Measures

1. Number of Severe Adverse Events (SAE) [Baseline to week 51]

2. Number of Treatment Emergent Adverse Events (TEAE) [Baseline to week 51]

3. Development of Anti-velaglucerase Alfa Antibody [Baseline to week51]

4. Number of Infusion- Related Adverse Events [Baseline to week 51]

5. Number of Patients With Concomitant Medication [Baseline to week 51]

Secondary Outcome Measures

1. Change From Baseline in Hemoglobin Concentration [Baseline to week 51]

2. Change From Baseline in Platelet Count [Baseline to week 51]

3. Change From Baseline in Liver Volume, Normalized to Body Weight [Baseline to week 51]

4. Change From Baseline in Spleen Volume, Normalized to Body Weight [Baseline to week 51]

5. Change From Baseline in Plasma Chitotriosidase Levels [Baseline to week 51]

6. Change From Baseline in CCL18 Levels [Baseline to week 51]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The patient has a documented diagnosis of Gaucher disease

• The patient is at least 2 years of age

• 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

Patients who are switched from imiglucerase ERT must meet the following additional criteria:

• Received treatment with imiglucerase for a minimum of 12 consecutive months

• Meet predefined limits for hemoglobin concentration and platelet counts

Patients naïve to treatment for Gaucher disease must meet the following additional criteria:

• Not received treatment for Gaucher disease (investigational or approved products) within 12 months prior to study entry

• Have Gaucher disease related anemia and at least one of the following: moderate splenomegaly or, Gaucher disease-related thrombocytopenia or Gaucher disease-related enlarged liver

Exclusion Criteria:

• Treatment with any investigational drug or device within the 30 days prior to study entry (time of informed consent); such use during the study is not permitted

• Positive for hepatitis B or hepatitis C.

• Non-Gaucher disease related anemia

• 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

• 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 or is unlikely to complete the study, as determined by the Investigator

• The patient has experienced a severe (grade 3 or higher) infusion-related hypersensitivity reaction (anaphylactic or anaphylactoid reaction) to any ERT (approved or investigational)

• Currently receiving red blood cell growth factor, (eg, erythropoietin) or chronic systemic corticosteroids in the last 6 months

• Patient has had a splenectomy or the patient has an active, clinically significant spleen infarction within 12 months of screening

• Patient has worsening bone necrosis within 12 months of screening

• The patient is pregnant or lactating.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hamamatsu University School of Medicine	Hamamatsu	Shizuoka	Japan	431-3192
2	The Jikei University School of Medicine	Minato-ku	Toyko	Japan	105-8461
3	Osaka City University Hospital	Osaka		Japan	545-0051

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01614574
• Other Study ID Numbers: HGT-GCB-087
• First Posted: Jun 8, 2012
• Last Update Posted: Jun 28, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Gaucher Disease

Study Results

Participant Flow

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
Overall Participants	6
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	20 (10.62)
Age, Customized (Count of Participants)
<=18 years	4 66.7%
Between 18 and 65 years	2 33.3%
Sex: Female, Male (Count of Participants)
Female	1 16.7%
Male	5 83.3%
Region of Enrollment (Count of Participants)
JAPAN	6 100%
Hemoglobin Concentration ((g/dL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [(g/dL)]	13.77 (0.954)
Platelet Count ((x 10^9 platelets/L)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [(x 10^9 platelets/L)]	182.9 (32.05)
Normalized liver volume ((% of Body Weight)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [(% of Body Weight)]	1.92 (0.342)
Normalized spleen volume ((% of Body Weight)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [(% of Body Weight)]	0.39 (0.067)
Plasma chitotriosidase ((nmol/mL/h)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [(nmol/mL/h)]	1243.7 (344.46)
CCL18 levels ((ng/mL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [(ng/mL)]	134.8 (132.26)

Outcome Measures

1. Primary Outcome

Title	Number of Severe Adverse Events (SAE)
Time Frame	Baseline to week 51

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
Measure Participants	6
Number [events]	1

2. Primary Outcome

Title	Number of Treatment Emergent Adverse Events (TEAE)
Time Frame	Baseline to week 51

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
Measure Participants	6
Number [events]	31

3. Primary Outcome

Title	Development of Anti-velaglucerase Alfa Antibody
Time Frame	Baseline to week51

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
Measure Participants	6
Positive (Baseline)	0 0%
Negative (Baseline)	6 100%
Positive (Week 51)	0 0%
Negative (Week 51)	6 100%

4. Primary Outcome

Title	Number of Infusion- Related Adverse Events
Time Frame	Baseline to week 51

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
Measure Participants	6
Number [events]	2

5. Primary Outcome

Title	Number of Patients With Concomitant Medication
Time Frame	Baseline to week 51

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
Measure Participants	6
Number [participants]	6 100%

6. Secondary Outcome

Title	Change From Baseline in Hemoglobin Concentration
Time Frame	Baseline to week 51

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
Measure Participants	6
Mean (Standard Deviation) [(g/dL)]	0.05 (0.729)

7. Secondary Outcome

Title	Change From Baseline in Platelet Count
Time Frame	Baseline to week 51

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
Measure Participants	6
Mean (Standard Deviation) [(x 10^9 platelets/L)]	13.8 (35.75)

8. Secondary Outcome

Title	Change From Baseline in Liver Volume, Normalized to Body Weight
Time Frame	Baseline to week 51

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
Measure Participants	6
Mean (Standard Deviation) [(% of Body Weight)]	0.05 (0.148)

9. Secondary Outcome

Title	Change From Baseline in Spleen Volume, Normalized to Body Weight
Time Frame	Baseline to week 51

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
Measure Participants	6
Mean (Standard Deviation) [(% of Body Weight)]	0.39 (0.067)

10. Secondary Outcome

Title	Change From Baseline in Plasma Chitotriosidase Levels
Time Frame	Baseline to week 51

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
Measure Participants	6
Mean (Standard Deviation) [(nmol/mL/h)]	-47.3 (64.44)

11. Secondary Outcome

Title	Change From Baseline in CCL18 Levels
Time Frame	Baseline to week 51

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
Measure Participants	6
Mean (Standard Deviation) [(ng/mL)]	5.2 (10.59)

Adverse Events

Arm/Group Title	VPRIV® (15-60 U/kg)
Arm/Group Description	Administered as an intravenous (IV) infusion over a 60 minute period.
All Cause Mortality
	VPRIV® (15-60 U/kg)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	VPRIV® (15-60 U/kg)
	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)
Eye disorders
RETINAL DETACHMENT	1/6 (16.7%)	1
Other (Not Including Serious) Adverse Events
	VPRIV® (15-60 U/kg)
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Eye disorders
RETINOPATHY PROLIFERATIVE	1/6 (16.7%)	1
VISUAL ACUITY REDUCED	1/6 (16.7%)	1
Gastrointestinal disorders
ABDOMINAL PAIN UPPER	1/6 (16.7%)	1
CHEILITIS	1/6 (16.7%)	1
ENTERITIS	1/6 (16.7%)	1
NAUSEA	1/6 (16.7%)	1
VOMITING	1/6 (16.7%)	1
General disorders
OEDEMA PERIPHERAL	1/6 (16.7%)	1
SUBMANDIBULAR MASS	1/6 (16.7%)	1
Infections and infestations
GASTROENTERITIS	1/6 (16.7%)	2
HAND-FOOT-AND-MOUTH DISEASE	1/6 (16.7%)	1
HORDEOLUM	1/6 (16.7%)	1
NASOPHARYNGITIS	6/6 (100%)	9
OTITIS MEDIA	1/6 (16.7%)	1
Injury, poisoning and procedural complications
CONTUSION	3/6 (50%)	3
JOINT SPRAIN	1/6 (16.7%)	1
LIMB INJURY	1/6 (16.7%)	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA	2/6 (33.3%)	2
Nervous system disorders
HEADACHE	1/6 (16.7%)	1
LOSS OF CONSCIOUSNESS	1/6 (16.7%)	1
MYOCLONUS	1/6 (16.7%)	1
Psychiatric disorders
ADJUSTMENT DISORDER	1/6 (16.7%)	1
Reproductive system and breast disorders
MENSTRUATION IRREGULAR	1/6 (16.7%)	1
Respiratory, thoracic and mediastinal disorders
COUGH	1/6 (16.7%)	1
EPISTAXIS	1/6 (16.7%)	2
PHARYNGOLARYNGEAL PAIN	1/6 (16.7%)	1
TACHYPNOEA	1/6 (16.7%)	1
Skin and subcutaneous tissue disorders
ACNE	1/6 (16.7%)	1
ALOPECIA	1/6 (16.7%)	1
ECZEMA	1/6 (16.7%)	1
URTICARIA	1/6 (16.7%)	1

Limitations/Caveats

All 6 enrolled patients received previous long-term treatment with the enzyme replacement therapy (ERT), imiglucerase. Key therapeutic parameters were expected to indicate stability after switching from imiglucerase.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Shire's agreements with investigators vary. All agreements provide Shire the right to embargo communications regarding trial results prior to public release for a period ≤180 days from the time submitted to Shire for review. Shire does not prohibit publication, but can require the removal of confidential information (excluding trial results) and can request postponement of a single-center publication until after disclosure of the trial's multi-center publication