Clinical trial NCT01842841: Multicenter Extension Study of Velaglucerase Alfa in Japanese Patients With Gaucher Disease
Official title: A Multicenter, Open-label Extension Study of Velaglucerase Alfa Enzyme Replacement Therapy in Japanese Patients With Gaucher Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gaucher Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
First posted: 2013-04-30
Enrollment: 5
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of Participants With Drug-related Adverse Events (AEs), Infusion-related AEs, and Serious AEs (SAEs)
timeFrame: From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
measure: Number of Participants Using Concomitant Medication
timeFrame: From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
measure: Number of Participants With Abnormal and Clinically Significant Laboratory Test Results
timeFrame: From Week 65 until the end of study (Week 155)
measure: Number of Participants With Positive Anti-Velaglucerase Alfa Antibodies
timeFrame: From Week 65 until the end of study (Week 155)
Secondary outcomes:
measure: Change From Baseline in Hemoglobin Concentration at Week 101
timeFrame: Baseline, Week 101
measure: Change From Baseline in Platelet Count at Week 101
timeFrame: Baseline, Week 101
measure: Change From Baseline in Liver Volume Normalized to Body Weight at Week 103
timeFrame: Baseline, Week 103
measure: Change From Baseline in Spleen Volume Normalized to Body Weight at Week 103
timeFrame: Baseline, Week 103
measure: Change From Baseline in Bone Mineral Density (BMD) at Week 103: Z Score
timeFrame: Baseline, Week 103
measure: Change From Baseline in Bone Mineral Density (BMD) at Week 103: T-Score
timeFrame: Baseline, Week 103
measure: Change From Baseline in Bone Marrow Burden (BMB) Score at Week 103
timeFrame: Baseline, Week 103
measure: Change From Baseline in Growth Velocity at Week 101 : Height Z-Score
timeFrame: Baseline, Week 101
measure: Change From Baseline in Skeletal Age at Week 103: Z-Score
timeFrame: Baseline, Week 103
measure: Change From Baseline in Plasma Chitotriosidase Levels at Week 101
timeFrame: Baseline, Week 101
measure: Number of Participants With Change From Baseline in Neurological Status at Week 103
timeFrame: Baseline, Week 103
measure: Change From Baseline in Chemokine [C-C Motif] Ligand 18 (CCL18) Levels at Week 101
timeFrame: Baseline, Week 101
Other outcomes:
Locations:
city: Hamamatsu
country: Japan
facility: Hamamatsu University School of Medicine
state: Shizuoka
city: Okubo
country: Japan
facility: Iwata City Hospital
state: Shizuoka
city: Minato-ku
country: Japan
facility: The Jikei University School of Medicine
state: Tokyo
city: Chiba
country: Japan
facility: Chiba Children's Hospital
city: Osaka
country: Japan
facility: Osaka City University Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.