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

Gaucher Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05529992
• Other study ID #: TAK-669-3001
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 3, 2023
• Est. completion date: August 25, 2024

Study information

• Verified date: February 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: August 25, 2024
• Est. primary completion date: August 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Gaucher Disease

Intervention

Drug:
• Velaglucerase Alfa
VPRIV intravenous infusion every other week for 60 minutes.

Locations

Country	Name	City	State
China	Beijing Children's Hospital, Capital Medical University	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	Guangzhou Women and Children's Medical Center	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	Lanzhou University Second Hospital	Lanzhou	Gansu
China	Nanjing Children's Hospital	Nanjing	Jiangsu
China	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences	Tianjin	Tianjin
China	Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from Baseline to Week 53 in Hemoglobin Concentration		Baseline, up to Week 53
Secondary	Change from Baseline to Week 53 in Platelet Count		Baseline, up to Week 53
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Cmax: Maximum Observed Serum Concentration for VPRIV at Week 37		Post-dose (up to 60 minutes) of Week 37
Secondary	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
Secondary	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
Secondary	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
Secondary	Oral Clearance (CL) for VPRIV		Pre-dose and at multiple timepoints (up to 120 minutes) post-dose on Day 1 of Week 1
Secondary	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
Secondary	Percentage Change from Baseline to Week 53 in Biomarker: Plasma Chemokine [C-C motif] Ligand 18		Baseline, up to Week 53
Secondary	Percentage Change from Baseline to Week 53 in Biomarker: Glucosylsphingosine		Baseline, up to Week 53

External Links

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