A Study of Velaglucerase Alfa (VPRIV) in Chinese Children, Teenagers, and Adults With Type 1 Gaucher Disease

Study Overview
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Brief Summary
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The main purpose of this study is to observe the side effects of VPRIV in participants with type 1 Gaucher disease who are either treatment-naïve (newly diagnosed) or who are currently being treated with enzyme replacement therapy (ERT). Participants will receive VPRIV intravenously during the treatment period (up to 51 weeks), followed by the end-of-treatment (EOT) visit after 2 weeks.

Detailed Description
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The drug being tested in this study is called Velaglucerase Alfa (VPRIV). VPRIV will be tested to treat participants with type 1 Gaucher disease. This study will look at the safety, efficacy and pharmacokinetics of VPRIV in the treatment of type 1 Gaucher disease. The study will enroll approximately 20 participants with Gaucher disease. The study comprises a screening period (Day -21 through Day -4), baseline period (Day -3 through Day 0), treatment period (Week 1 to Week 51), and safety follow-up period. Participants will be assigned to the following drug administration: • Velaglucerase Alfa (VPRIV) Participants will receive VPRIV as intravenous (IV) infusion every other week from Week 1 through Week 51 during the Treatment Period. Percentage of participants with at least one serious treatment-emergent adverse event (TEAE) will be evaluated throughout the study. This multi-center trial will be conducted in China. The overall time to participate in this study is approximately 59 weeks. Participants will make a safety follow-up telephone call or visit to the site after 30 (±7) days of the last infusion of the study drug.

Official Title
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A Multicenter, Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Velaglucerase Alfa in Chinese Subjects With Type 1 Gaucher Disease

Conditions
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Gaucher Disease

Intervention / Treatment
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* Drug: Velaglucerase Alfa


Participation Criteria
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Eligibility Criteria
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Inclusion: Has a documented, confirmed diagnosis of type 1 Gaucher disease based on the following, as determined by the investigator: Decreased glucocerebrosidase (GCB) activity level that is ≤30% of normal or Decreased GCB activity level that is >30% of normal, but with confirmation of genetic mutation test Is at least 2 years of age, inclusive, at screening Is naive to treatment for Gaucher disease (Has not received treatment for Gaucher disease [investigational or approved products] within the 12 months prior to screening) OR Is receiving or has recently received Imiglucerase ERT (Has received Imiglucerase treatment within the 12 months prior to screening and not within the 14 days prior to screening) Has Gaucher disease-related hematological abnormalities, defined as Hemoglobin levels of ≥1 g/dL below the lower limit of normal for their age and gender AND/OR A platelet count of <90 × 10^9/L below the lower limit of normal for their age and gender Has Gaucher disease-related viscera abnormalities, defined as the following: Participant has at least moderate splenomegaly, assessed by palpation (2 to 3 cm below the left costal margin), or by abdominal radiology scan (magnetic resonance imaging [MRI] or computed tomography [CT] scan, with spleen volume >5 times normal) AND/OR Participant has hepatomegaly, assessed by palpation or by abdominal radiology scan (MRI or CT scan); Participants who have undergone splenectomy must have satisfied these criteria for this study. Exclusion: Has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease as assessed by the investigator Has had a splenectomy or an active, clinically significant spleen infarction within the 12 months prior to screening Has received treatment with any investigational drug or device within 30 days prior to screening, or within 5 half-lives of that investigational product, whichever is greater; such treatment during the study will not be permitted Is currently receiving red blood cell growth factor (eg, erythropoietin), chronic systemic corticosteroids, or has been on such treatment within the 6 months prior to screening Presents with non-Gaucher disease related exacerbated anemia at screening Has experienced a severe (grade 3 or higher) infusion-related hypersensitivity reaction (anaphylactic or anaphylactoid reaction) to any ERT (approved or investigational)

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Velaglucerase Alfa (VPRIV)<br>Participants will receive VPRIV intravenous infusion once every other week (EOW) for 60 (+10) minutes as per physician treatment plan for up to 51 weeks. | Drug: Velaglucerase Alfa<br>* VPRIV intravenous infusion every other week for 60 minutes.<br>* Other names: VPRIV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With at Least One Serious Treatment-Emergent Adverse Events (TEAE) Throughout the Study | A TEAE is defined as any event emerging or manifesting at or after the initiation of the investigational product or any existing event that worsens in either intensity or frequency following exposure to the investigational product. An SAE is any untoward clinical manifestation of signs, symptoms, or outcomes (whether considered related to the investigational product or not) and at any dose: results in death, is life-threatening, requires in-patient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, or is an important medical event. | Up to 59 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With TEAEs | A TEAE is defined as any event emerging or manifesting at or after the initiation of the investigational product or any existing event that worsens in either intensity or frequency following exposure to the investigational product. | Up to 59 weeks | 
| Percentage of Participants With Infusion-related Reactions Throughout the Study Reported as Adverse Event | An infusion-related AE is defined as an AE that 1) begins either during or within 12 hours after the start of the infusion and 2) is judged as possibly or probably related to the study treatment. | Up to 59 weeks | 
| Percentage of Participants With Development of anti-VPRIV Antibodies, Including Neutralizing Antibodies Throughout the Study | Participants with the development of anti-VPRIV antibodies, including neutralizing antibodies will be assessed. | Up to 59 weeks | 
| Number of Participants With Clinically Significant Changes in Laboratory Assessments, Vital Signs Measurements, and Electrocardiogram (ECG) Measurements | Number of participants with clinically significant changes in laboratory parameters, vital signs, and 12-Lead electrocardiogram (ECG) findings will be reported. | Up to 59 weeks | 
| Change from Baseline to Week 53 in Hemoglobin Concentration |  | Baseline, up to Week 53 | 
| Change from Baseline to Week 53 in Platelet Count |  | Baseline, up to Week 53 | 
| Change from Baseline to Week 53 in Normalized Liver Volume | Normalized liver volume will be measured by abdominal magnetic resonance imaging (MRI) or computed tomography (CT) scan. Liver volume will be normalized for percent (%) body weight. | Baseline, up to Week 53 | 
| Change from Baseline to Week 53 in Normalized Spleen Volume | Normalized spleen volume will be measured by abdominal MRI or CT scan. Spleen volume will be normalized for % body weight. | Baseline, up to Week 53 | 
| Change from Baseline to Week 53 in Quality of Life (QoL) Questionnaire Assessment as Measured by Short Form-36 (SF-36), Version 2 | Participants greater than or equal to (≥)18 years-old will complete the SF-36 questionnaire. QoL assessment is not applicable for participants <5 years of age. The SF-36, version 2 is a self-administered, validated questionnaire designed to measure generic health-related QoL. This 36-item questionnaire measures 8 domains, including physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. Two summary scores, including the Physical Component Score and Mental Component Score, will be calculated ranging from 0 (worst) to 100 (best). Higher scores indicate better health status. | Baseline, up to Week 53 | 
| Change from Baseline to Week 53 in QoL Questionnaire Assessment as Measured by Childhood Health Questionnaire-Parent Form 50 (CHQ-PF50) | Participants from >5 and <18 years of age will complete the CHQ-PF50. QoL assessment is not applicable for participants <5 years of age. The CHQ-PF50 will assess the parent(s) or caregiver's impression of the following scales: global health, physical functioning, role/social limitations (emotional/behavioral and physical), bodily pain/discomfort, behavior, global behavior, mental health, self-esteem, general health perceptions, change in health, parental impact (emotional and time), family activities, and family cohesion. The total score will be calculated ranging from 0 (worst) to 100 (best). An increase in the CHQ-PF50 score indicates a more favorable assessment by the proxy of the child's health and/or well-being. | Baseline, up to Week 53 | 
| Cmax: Maximum Observed Serum Concentration for VPRIV at Week 1 |  | Pre-dose and at multiple timepoints (up to 120 minutes) post-dose on Day 1 of Week 1 | 
| Cmax: Maximum Observed Serum Concentration for VPRIV at Week 37 |  | Post-dose (up to 60 minutes) of Week 37 | 
| Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for VPRIV |  | Pre-dose and at multiple timepoints (up to 120 minutes) post-dose on Day 1 of Week 1 | 
| AUCinf: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for VPRIV |  | Pre-dose and at multiple timepoints (up to 120 minutes) post-dose on Day 1 of Week 1 | 
| Terminal Phase Elimination Half-life (T1/2) for VPRIV |  | Pre-dose and at multiple timepoints (up to 120 minutes) post-dose on Day 1 of Week 1 | 
| Oral Clearance (CL) for VPRIV |  | Pre-dose and at multiple timepoints (up to 120 minutes) post-dose on Day 1 of Week 1 | 
| Apparent Steady-state Volume of Distribution (Vss) for VPRIV |  | Pre-dose and at multiple timepoints (up to 120 minutes) post-dose on Day 1 of Week 1 | 
| Percentage Change from Baseline to Week 53 in Biomarker: Plasma Chemokine [C-C motif] Ligand 18 |  | Baseline, up to Week 53 | 
| Percentage Change from Baseline to Week 53 in Biomarker: Glucosylsphingosine |  | Baseline, up to Week 53 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VPRIV, Gaucher Disease