Clinical trial NCT05529992: A Study of Velaglucerase Alfa (VPRIV) in Chinese Children, Teenagers, and Adults With Type 1 Gaucher Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gaucher Disease
Keywords: VPRIV
Gaucher Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2022-09-07
Enrollment: 20
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: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of Participants With at Least One Serious Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to 56.2 weeks
Secondary outcomes:
measure: Percentage of Participants With TEAEs
timeFrame: Up to 56.2 weeks
measure: Percentage of Participants With Infusion-related Reactions Reported as an Adverse Event
timeFrame: Up to 56.2 weeks
measure: Percentage of Participants With Development of Anti-VPRIV Antibodies and Neutralizing Antibodies at Week 53
timeFrame: Week 53
measure: Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53
timeFrame: Week 53
measure: Number of Participants With Abnormal Changes in Laboratory Assessments at Week 53: Urinalysis
timeFrame: Week 53
measure: Number of Participants With at Least One Abnormal Change in an Infusion Vital Sign Parameter at Week 53
timeFrame: Week 53
measure: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements at Week 53
timeFrame: Week 53
measure: Change From Baseline to Week 53 in Hemoglobin Concentration
timeFrame: Baseline, Week 53
measure: Change From Baseline to Week 53 in Platelet Count
timeFrame: Baseline, Week 53
measure: Change From Baseline to Week 53 in Normalized Liver Volume
timeFrame: Baseline, Week 53
measure: Change From Baseline to Week 53 in Normalized Spleen Volume
timeFrame: Baseline, Week 53
measure: Change From Baseline to Week 53 in 36-item Short Form General Health Survey (SF-36) Scores
timeFrame: Baseline, Week 53
measure: Change From Baseline to Week 53 in Childhood Health Questionnaire-Parent Form 50 (CHQ-PF50) Scores
timeFrame: Baseline, Week 53
measure: Cmax: Maximum Observed Serum Concentration for VPRIV at Week 1
timeFrame: Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
measure: Serum Concentration for VPRIV at Week 37
timeFrame: Within 3 minutes prior to the end of the 60-minute infusion at Week 37
measure: Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for VPRIV
timeFrame: Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
measure: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for VPRIV
timeFrame: Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
measure: Terminal Phase Elimination Half-life (T1/2) for VPRIV
timeFrame: Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
measure: Oral Clearance (CL) for VPRIV
timeFrame: Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
measure: Apparent Steady-state Volume of Distribution (Vss) for VPRIV
timeFrame: Pre-dose and at multiple timepoints(up to 120 minutes post-dose on Day 1 of Week 1
measure: Percent Change From Baseline to Week 53 in Biomarker: Plasma Chemokine [C-C Motif] Ligand 18
timeFrame: Baseline, Week 53
measure: Percent Change From Baseline to Week 53 in Biomarker: Glucopsychosine
timeFrame: Baseline, Week 53
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Children's Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou Women and Children's Medical Center
state: Guangdong
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Wuhan
country: China
facility: Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Nanjing
country: China
facility: Nanjing Children's Hospital
state: Jiangsu
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: