Gaucher Disease
Conditions
Keywords
VPRIV, Gaucher Disease
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.
Interventions
VPRIV intravenous infusion every other week for 60 minutes.
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least One Serious Treatment-Emergent Adverse Event (TEAE) | Up to 56.2 weeks | Adverse event(AE)=any untoward medical occurrence in clinical investigation participant administered a drug;it does not necessarily have to have causal relationship with this treatment. AE can therefore be any unfavorable&unintended sign (example,clinically significant abnormal laboratory value),symptom/disease temporally associated with use of drug whether or not it is considered related to drug. TEAE=any event emerging or manifesting at or after initiation of investigational product or any existing event that worsens in either intensity or frequency following exposure to investigational product. SAE=any untoward clinical manifestation of signs, symptoms, or outcomes(whether considered related to investigational product or not)&at any dose: results in death,is life-threatening,requires in-patient hospitalization/prolongation of hospitalization,results in persistent/significant disability/incapacity,results in congenital abnormality/birth defect,or is an important medical event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With TEAEs | Up to 56.2 weeks | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory value), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. 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. |
| Percentage of Participants With Infusion-related Reactions Reported as an Adverse Event | Up to 56.2 weeks | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory value), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. An infusion-related AE was defined as an AE that 1) began either during or within 12 hours after the start of the infusion and 2) was judged as possibly or probably related to the study treatment. |
| Percentage of Participants With Development of Anti-VPRIV Antibodies and Neutralizing Antibodies at Week 53 | Week 53 | Percentages were rounded off to the nearest single decimal place. |
| Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Week 53 | Clinical laboratory assessments included hematology and serum chemistry. Any clinically significant changes in the clinical laboratory assessment values based on the investigator's interpretation were reported. Only categories with at least one participant with event are presented. |
| Number of Participants With Abnormal Changes in Laboratory Assessments at Week 53: Urinalysis | Week 53 | Any abnormal changes in the urinalysis assessment values based on the investigator's interpretation were reported. Urinalysis comprised of the following parameters: bilirubin, ketones, glucose, nitrite, occult blood, protein, and urobilinogen. |
| Number of Participants With at Least One Abnormal Change in an Infusion Vital Sign Parameter at Week 53 | Week 53 | Participants with atleast 1 abnormal change (above or below normal) in an infusion vital sign parameter of pulse, temperature, respiratory rate,& blood pressure were reported. Normal ranges for each vital sign parameter were, pulse (beats per minutes \[bpm\]): 40-100(≥12 years old), 55-95(≥6 but \<12 years old), 65-110(≥2 but \<6 years old); body temperature(degree Celsius\[˚C\]): 36.5 to 37.2(all age groups),respiration rate(breaths/minutes):12-24(≥12 years old),12-22 (≥6 but \<12 years old),20-30(≥2 but \<6 years old);systolic blood pressure(BP) \[millimeters of mercury{mm Hg}\]: high: ≥140 (≥18 years old), ≥20+ 80+ 2\*age(\<18 years old), low: \<90 (≥18 years old), \< -20+ 80+ 2\*age(\<18 years old); diastolic BP(mm Hg):high:≥90 (≥18 years old), ≥20+ (80+2\*age)\*(2/3) (\<18 years old) low: \<50 (≥18 years old), \< -20+ (80+2\*age)\*(2/3) (\<18 years old). As per planned analysis,data was collected in a combined manner for all participants irrespective of age. Only non-zero categories are presented. |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements at Week 53 | Week 53 | Participants with clinically significant changes in any ECG measurement, such as PR, QRS, QT, corrected QT intervals, and heart rate based on the investigator's interpretation were reported. |
| Change From Baseline to Week 53 in Platelet Count | Baseline, Week 53 | — |
| Change From Baseline to Week 53 in Normalized Liver Volume | Baseline, Week 53 | Normalized liver volume was measured by abdominal magnetic resonance imaging (MRI) or computed tomography (CT) scan. Liver volume was normalized for percent body weight. |
| Change From Baseline to Week 53 in Normalized Spleen Volume | Baseline, Week 53 | Spleen volume was normalized for percent body weight. |
| Change From Baseline to Week 53 in Hemoglobin Concentration | Baseline, Week 53 | — |
| Change From Baseline to Week 53 in Childhood Health Questionnaire-Parent Form 50 (CHQ-PF50) Scores | Baseline, Week 53 | The CHQ-PF-50 is a 50-item questionnaire to be completed by the parents or guardians of children between 5 and 18 years of age. The 50 questions measure 14 domains (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) which were summarized as the physical and psychological summary scores. Each summary score was transformed and could range from 0 to 100, with higher score indicating better physical and psychosocial health. A positive change from Baseline indicates improved well-being. |
| 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 | — |
| Serum Concentration for VPRIV at Week 37 | Within 3 minutes prior to the end of the 60-minute infusion at 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 | ng\*min/mL denotes nanograms\*minutes per milliliter. |
| 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 | mL/min/kg denotes milliliters per minutes per kilogram. |
| 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 | — |
| Percent Change From Baseline to Week 53 in Biomarker: Plasma Chemokine [C-C Motif] Ligand 18 | Baseline, Week 53 | — |
| Percent Change From Baseline to Week 53 in Biomarker: Glucopsychosine | Baseline, Week 53 | — |
| Change From Baseline to Week 53 in 36-item Short Form General Health Survey (SF-36) Scores | Baseline, Week 53 | SF-36 Version 2 is a multipurpose, participant completed, short-form health survey with 36 questions that consists of an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Physical component summary (PCS) is mostly contributed by physical function (PF), role physical (RP), bodily pain (BP), and general health (GH). Mental component summary (MCS) is mostly contributed by mental health (MH), role emotional (RE), social function (SF), and vitality (VT). Each component on the SF-36 item health survey is scored from 0 (best) to 100 (worst). Total score ranges from 0-100 for each component summary (i.e., PCS and MCS), where higher scores are associated with less disability and better quality of life. |
Countries
China
Participant flow
Recruitment details
Participants took part in the study at various investigative sites in China from 3 January 2023 to 5 August 2024.
Pre-assignment details
Participants with a diagnosis of type 1 Gaucher disease were enrolled in this study to receive velaglucerase alfa (VPRIV) as intravenous (IV) infusion.
Participants by arm
| Arm | Count |
|---|---|
| VPRIV Participants received VPRIV IV infusion at 60 U/kg body weight once EOW for 60 (+10) minutes up to Week 51. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | VPRIV |
|---|---|
| Age, Continuous | 14.3 years STANDARD_DEVIATION 9.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 20 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 19 / 20 |
| serious Total, serious adverse events | 4 / 20 |
Outcome results
Primary
Percentage of Participants With at Least One Serious Treatment-Emergent Adverse Event (TEAE)
Adverse event(AE)=any untoward medical occurrence in clinical investigation participant administered a drug;it does not necessarily have to have causal relationship with this treatment. AE can therefore be any unfavorable&unintended sign (example,clinically significant abnormal laboratory value),symptom/disease temporally associated with use of drug whether or not it is considered related to drug. TEAE=any event emerging or manifesting at or after initiation of investigational product or any existing event that worsens in either intensity or frequency following exposure to investigational product. SAE=any untoward clinical manifestation of signs, symptoms, or outcomes(whether considered related to investigational product or not)&at any dose: results in death,is life-threatening,requires in-patient hospitalization/prolongation of hospitalization,results in persistent/significant disability/incapacity,results in congenital abnormality/birth defect,or is an important medical event.
Time frame: Up to 56.2 weeks
Population: The Safety Set (SAF) included all participants in the ITT Set who received at least 1 dose of VPRIV.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VPRIV | Percentage of Participants With at Least One Serious Treatment-Emergent Adverse Event (TEAE) | 20 percentage of participants |
Secondary
Apparent Steady-state Volume of Distribution (Vss) for VPRIV
Time frame: Pre-dose and at multiple timepoints(up to 120 minutes post-dose on Day 1 of Week 1
Population: The PK Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VPRIV | Apparent Steady-state Volume of Distribution (Vss) for VPRIV | 96.3 milliliters per kilogram (mL/kg) | Standard Deviation 52 |
Secondary
AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for VPRIV
ng\*min/mL denotes nanograms\*minutes per milliliter.
Time frame: Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
Population: The PK Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VPRIV | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for VPRIV | 235000 ng*min/mL | Standard Deviation 85000 |
Secondary
Change From Baseline to Week 53 in 36-item Short Form General Health Survey (SF-36) Scores
SF-36 Version 2 is a multipurpose, participant completed, short-form health survey with 36 questions that consists of an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Physical component summary (PCS) is mostly contributed by physical function (PF), role physical (RP), bodily pain (BP), and general health (GH). Mental component summary (MCS) is mostly contributed by mental health (MH), role emotional (RE), social function (SF), and vitality (VT). Each component on the SF-36 item health survey is scored from 0 (best) to 100 (worst). Total score ranges from 0-100 for each component summary (i.e., PCS and MCS), where higher scores are associated with less disability and better quality of life.
Time frame: Baseline, Week 53
Population: The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VPRIV | Change From Baseline to Week 53 in 36-item Short Form General Health Survey (SF-36) Scores | Physical Component Summary | 7.015 score on a scale | Standard Deviation 5.8464 |
| VPRIV | Change From Baseline to Week 53 in 36-item Short Form General Health Survey (SF-36) Scores | Mental Component Summary | 2.858 score on a scale | Standard Deviation 12.5103 |
Secondary
Change From Baseline to Week 53 in Childhood Health Questionnaire-Parent Form 50 (CHQ-PF50) Scores
The CHQ-PF-50 is a 50-item questionnaire to be completed by the parents or guardians of children between 5 and 18 years of age. The 50 questions measure 14 domains (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) which were summarized as the physical and psychological summary scores. Each summary score was transformed and could range from 0 to 100, with higher score indicating better physical and psychosocial health. A positive change from Baseline indicates improved well-being.
Time frame: Baseline, Week 53
Population: The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VPRIV | Change From Baseline to Week 53 in Childhood Health Questionnaire-Parent Form 50 (CHQ-PF50) Scores | Physical Summary Score | -0.02 score on a scale | Standard Deviation 12.745 |
| VPRIV | Change From Baseline to Week 53 in Childhood Health Questionnaire-Parent Form 50 (CHQ-PF50) Scores | Psychosocial Summary Score | 0.38 score on a scale | Standard Deviation 11.462 |
Secondary
Change From Baseline to Week 53 in Hemoglobin Concentration
Time frame: Baseline, Week 53
Population: The ITT Set included all participants who signed the ICF (and assent form, if applicable) and were eligible for the study based on the defined inclusion/exclusion criteria. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VPRIV | Change From Baseline to Week 53 in Hemoglobin Concentration | 2.34 grams per deciliter (g/dL) | Standard Deviation 1.305 |
Secondary
Change From Baseline to Week 53 in Normalized Liver Volume
Normalized liver volume was measured by abdominal magnetic resonance imaging (MRI) or computed tomography (CT) scan. Liver volume was normalized for percent body weight.
Time frame: Baseline, Week 53
Population: The ITT Set included all participants who signed the ICF (and assent form, if applicable) and were eligible for the study based on the defined inclusion/exclusion criteria. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VPRIV | Change From Baseline to Week 53 in Normalized Liver Volume | -1.11 percentage of body weight (%BW) | Standard Deviation 0.917 |
Secondary
Change From Baseline to Week 53 in Normalized Spleen Volume
Spleen volume was normalized for percent body weight.
Time frame: Baseline, Week 53
Population: The ITT Set included all participants who signed the ICF (and assent form, if applicable) and were eligible for the study based on the defined inclusion/exclusion criteria. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VPRIV | Change From Baseline to Week 53 in Normalized Spleen Volume | -3.09 % BW | Standard Deviation 1.627 |
Secondary
Change From Baseline to Week 53 in Platelet Count
Time frame: Baseline, Week 53
Population: The ITT Set included all participants who signed the ICF (and assent form, if applicable) and were eligible for the study based on the defined inclusion/exclusion criteria. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VPRIV | Change From Baseline to Week 53 in Platelet Count | 42.1 platelets*10^9/liter | Standard Deviation 27.68 |
Secondary
Cmax: Maximum Observed Serum Concentration for VPRIV at Week 1
Time frame: Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
Population: The Pharmacokinetic (PK) Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VPRIV | Cmax: Maximum Observed Serum Concentration for VPRIV at Week 1 | 5220 nanograms per milliliter (ng/mL) | Standard Deviation 1610 |
Secondary
Number of Participants With Abnormal Changes in Laboratory Assessments at Week 53: Urinalysis
Any abnormal changes in the urinalysis assessment values based on the investigator's interpretation were reported. Urinalysis comprised of the following parameters: bilirubin, ketones, glucose, nitrite, occult blood, protein, and urobilinogen.
Time frame: Week 53
Population: The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis for the specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VPRIV | Number of Participants With Abnormal Changes in Laboratory Assessments at Week 53: Urinalysis | Urinalysis: Bilirubin | 1 Participants |
| VPRIV | Number of Participants With Abnormal Changes in Laboratory Assessments at Week 53: Urinalysis | Urinalysis: Ketones | 0 Participants |
| VPRIV | Number of Participants With Abnormal Changes in Laboratory Assessments at Week 53: Urinalysis | Urinalysis: Glucose | 1 Participants |
| VPRIV | Number of Participants With Abnormal Changes in Laboratory Assessments at Week 53: Urinalysis | Urinalysis: Nitrite | 1 Participants |
| VPRIV | Number of Participants With Abnormal Changes in Laboratory Assessments at Week 53: Urinalysis | Urinalysis: Occult Blood | 7 Participants |
| VPRIV | Number of Participants With Abnormal Changes in Laboratory Assessments at Week 53: Urinalysis | Urinalysis: Protein | 3 Participants |
| VPRIV | Number of Participants With Abnormal Changes in Laboratory Assessments at Week 53: Urinalysis | Urinalysis: Urobilinogen | 3 Participants |
Secondary
Number of Participants With at Least One Abnormal Change in an Infusion Vital Sign Parameter at Week 53
Participants with atleast 1 abnormal change (above or below normal) in an infusion vital sign parameter of pulse, temperature, respiratory rate,& blood pressure were reported. Normal ranges for each vital sign parameter were, pulse (beats per minutes \[bpm\]): 40-100(≥12 years old), 55-95(≥6 but \<12 years old), 65-110(≥2 but \<6 years old); body temperature(degree Celsius\[˚C\]): 36.5 to 37.2(all age groups),respiration rate(breaths/minutes):12-24(≥12 years old),12-22 (≥6 but \<12 years old),20-30(≥2 but \<6 years old);systolic blood pressure(BP) \[millimeters of mercury{mm Hg}\]: high: ≥140 (≥18 years old), ≥20+ 80+ 2\*age(\<18 years old), low: \<90 (≥18 years old), \< -20+ 80+ 2\*age(\<18 years old); diastolic BP(mm Hg):high:≥90 (≥18 years old), ≥20+ (80+2\*age)\*(2/3) (\<18 years old) low: \<50 (≥18 years old), \< -20+ (80+2\*age)\*(2/3) (\<18 years old). As per planned analysis,data was collected in a combined manner for all participants irrespective of age. Only non-zero categories are presented.
Time frame: Week 53
Population: The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV. Number analyzed is the number of participants with data available for analysis for the specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VPRIV | Number of Participants With at Least One Abnormal Change in an Infusion Vital Sign Parameter at Week 53 | Pulse: Above Normal | 15 Participants |
| VPRIV | Number of Participants With at Least One Abnormal Change in an Infusion Vital Sign Parameter at Week 53 | Body Temperature: Above Normal | 1 Participants |
| VPRIV | Number of Participants With at Least One Abnormal Change in an Infusion Vital Sign Parameter at Week 53 | Body Temperature: Below Normal | 18 Participants |
| VPRIV | Number of Participants With at Least One Abnormal Change in an Infusion Vital Sign Parameter at Week 53 | Respiratory Rate: Above Normal | 9 Participants |
| VPRIV | Number of Participants With at Least One Abnormal Change in an Infusion Vital Sign Parameter at Week 53 | Systolic BP: Above Normal | 11 Participants |
| VPRIV | Number of Participants With at Least One Abnormal Change in an Infusion Vital Sign Parameter at Week 53 | Systolic BP: Below Normal | 5 Participants |
| VPRIV | Number of Participants With at Least One Abnormal Change in an Infusion Vital Sign Parameter at Week 53 | Diastolic BP: Above Normal | 8 Participants |
| VPRIV | Number of Participants With at Least One Abnormal Change in an Infusion Vital Sign Parameter at Week 53 | Diastolic BP: Below Normal | 3 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements at Week 53
Participants with clinically significant changes in any ECG measurement, such as PR, QRS, QT, corrected QT intervals, and heart rate based on the investigator's interpretation were reported.
Time frame: Week 53
Population: The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VPRIV | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements at Week 53 | 1 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53
Clinical laboratory assessments included hematology and serum chemistry. Any clinically significant changes in the clinical laboratory assessment values based on the investigator's interpretation were reported. Only categories with at least one participant with event are presented.
Time frame: Week 53
Population: The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis for the specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Hematology: Erythrocytes Mean Corpuscular Hemoglobin Concentration | 2 Participants |
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Hematology: Erythrocytes Mean Corpuscular Hemoglobin | 3 Participants |
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Hematology: Erythrocytes Mean Corpuscular Volume | 2 Participants |
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Hematology: Erythrocytes | 2 Participants |
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Hematology: Hematocrit | 5 Participants |
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Hematology: Hemoglobin | 4 Participants |
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Hematology: Leukocytes | 2 Participants |
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Hematology: Lymphocytes | 1 Participants |
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Hematology: Monocytes | 1 Participants |
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Hematology: Neutrophils | 2 Participants |
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Hematology: Platelets | 14 Participants |
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Serum Chemistry: Bilirubin | 3 Participants |
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Serum Chemistry: Ferritin | 5 Participants |
| VPRIV | Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | Serum Chemistry: Iron | 2 Participants |
Secondary
Oral Clearance (CL) for VPRIV
mL/min/kg denotes milliliters per minutes per kilogram.
Time frame: Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
Population: The PK Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VPRIV | Oral Clearance (CL) for VPRIV | 7.27 mL/min/kg | Standard Deviation 2.87 |
Secondary
Percentage of Participants With Development of Anti-VPRIV Antibodies and Neutralizing Antibodies at Week 53
Percentages were rounded off to the nearest single decimal place.
Time frame: Week 53
Population: The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VPRIV | Percentage of Participants With Development of Anti-VPRIV Antibodies and Neutralizing Antibodies at Week 53 | Anti-VPRIV Antibodies | 15.8 percentage of participants |
| VPRIV | Percentage of Participants With Development of Anti-VPRIV Antibodies and Neutralizing Antibodies at Week 53 | Neutralizing Antibodies | 10.5 percentage of participants |
Secondary
Percentage of Participants With Infusion-related Reactions Reported as an Adverse Event
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory value), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. An infusion-related AE was defined as an AE that 1) began either during or within 12 hours after the start of the infusion and 2) was judged as possibly or probably related to the study treatment.
Time frame: Up to 56.2 weeks
Population: The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VPRIV | Percentage of Participants With Infusion-related Reactions Reported as an Adverse Event | 5 percentage of participants |
Secondary
Percentage of Participants With TEAEs
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory value), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. 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.
Time frame: Up to 56.2 weeks
Population: The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VPRIV | Percentage of Participants With TEAEs | 95 percentage of participants |
Secondary
Percent Change From Baseline to Week 53 in Biomarker: Glucopsychosine
Time frame: Baseline, Week 53
Population: The ITT Set included all participants who signed the ICF (and assent form, if applicable) and were eligible for the study based on the defined inclusion/exclusion criteria. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VPRIV | Percent Change From Baseline to Week 53 in Biomarker: Glucopsychosine | -63.88 percent change | Standard Deviation 14.359 |
Secondary
Percent Change From Baseline to Week 53 in Biomarker: Plasma Chemokine [C-C Motif] Ligand 18
Time frame: Baseline, Week 53
Population: The ITT Set included all participants who signed the ICF (and assent form, if applicable) and were eligible for the study based on the defined inclusion/exclusion criteria. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VPRIV | Percent Change From Baseline to Week 53 in Biomarker: Plasma Chemokine [C-C Motif] Ligand 18 | -58.94 percent change | Standard Deviation 14.339 |
Secondary
Serum Concentration for VPRIV at Week 37
Time frame: Within 3 minutes prior to the end of the 60-minute infusion at Week 37
Population: The PK Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VPRIV | Serum Concentration for VPRIV at Week 37 | 3450 ng/mL | Standard Deviation 1390 |
Secondary
Terminal Phase Elimination Half-life (T1/2) for VPRIV
Time frame: Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
Population: The PK Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VPRIV | Terminal Phase Elimination Half-life (T1/2) for VPRIV | 10.12 min | Standard Deviation 2.81 |
Secondary
Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for VPRIV
Time frame: Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
Population: The PK Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VPRIV | Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for VPRIV | 49.00 minutes (min) |