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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Gaucher Disease
• Intervention / Treatment: Drug: Velaglucerase Alfa

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100045
      • Beijing Children's Hospital, Capital Medical University
    • Beijing, Beijing, China, 100039
      • Chinese PLA General Hospital
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
  • Gansu
    • Lanzhou, Gansu, China, 730030
      • Lanzhou University Second Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510623
      • Guangzhou Women And Children's Medical Center
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The Second Hospital of Hebei Medical University
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Children's Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

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

Description

Inclusion:

• Has a documented, confirmed diagnosis of type 1 Gaucher disease based on the following, as determined by the investigator:

  1. Decreased glucocerebrosidase (GCB) activity level that is ≤30% of normal or
  2. 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

  1. Hemoglobin levels of ≥1 g/dL below the lower limit of normal for their age and gender AND/OR
  2. 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)

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 (VPRIV); 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; VPRIV intravenous infusion every other week for 60 minutes.; Other Names: VPRIV

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2023
• Primary Completion (Estimated): August 25, 2024
• Study Completion (Estimated): August 25, 2024

Study Registration Dates

• First Submitted: September 2, 2022
• First Submitted That Met QC Criteria: September 2, 2022
• First Posted (Actual): September 7, 2022

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Gaucher Disease; VPRIV
• 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: TAK-669-3001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No