Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2012-003427-38 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Gaucher disease has been classified into 3 clinical subtypes based on the presence or absence of neurological symptoms and the severity of these neurological symptoms. Patients with type 2 Gaucher disease present with acute neurological deterioration, and those with type 3 disease typically display a more sub acute neurological course. Type 1 Gaucher disease, the most common form accounting for more than 90% of all Gaucher disease cases, does not involve the central nervous system.
The purpose of this clinical research study is to investigate the safety and effectiveness of velaglucerase alfa in patients with type 3 Gaucher disease.
Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to the deficiency of functional GCB, glucocerebroside accumulates within the macrophages leading to cellular engorgement, organomegaly, and organ system dysfunction. Gaucher disease has been classified into 3 clinical subtypes based on the presence or absence of neurological symptoms and severity of neurological symptoms. Patients with type 2 Gaucher disease present with acute neurological deterioration, and those with type 3 Gaucher disease typically display a more sub acute neurological course; type 1 Gaucher disease, the most common form accounting for more than 90% of all cases, does not involve the central nervous system.
Velaglucerase alfa is an approved enzyme replacement therapy (ERT) for pediatric and adult patients with type 1 Gaucher disease. ERTs have been proven to reduce organomegaly, improve hematological parameters and positively impact health-related quality of life; ERTs have not been shown to cross the blood brain barrier and as a result have shown limited ability to improve the neurological (Central Nervous System; CNS) manifestations associated with Gaucher disease.
This study will provide a basis for exploring the efficacy and safety of velaglucerase alfa in patients with type 3 Gaucher disease.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| velaglucerase alfa | Experimental | IV infusion, 60 U/kg, every other week for 1 year |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| velaglucerase alfa | Biological | lyophilized powder, intravenous infusion, units, Every other week (EOW) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to 12 Months (Week 53) in Hemoglobin Concentration | Hemoglobin concentration was measured as part of the hematology panel or measured separately when the hematology panel was not scheduled. Samples were measured by a central laboratory. Baseline is the modified baseline hemoglobin concentration, the average of the values from screening, baseline, and Week 1/Day 1. A positive change from baseline indicates that hemoglobin concentration increased. | Baseline, Week 53 or end of study |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to 12 Months (Week 53) in Platelet Count | Platelet count was measured at a central laboratory as part of the hematology panel. Baseline is the modified baseline platelet count, the average of the values from screening, baseline and Week 1/Day 1. A positive change from baseline indicates that platelet count increased. | Baseline, Week 53 |
Not provided
Inclusion Criteria: Each patient must meet the following criteria to be enrolled in this study.
The patient has a confirmed diagnosis of type 3 Gaucher disease.
The patient is ≥ 2 and < 18 years of age at the time of enrollment.
The patient is either näive to treatment or has not received treatment (investigational or approved) for Gaucher disease within 12 months prior to study entry.
The patient has Gaucher disease-related anemia, defined as hemoglobin concentration below the lower limit of normal for age and sex.
AND ONE OR MORE OF THE FOLLOWING THREE CRITERIA
Patients who have undergone splenectomy may still be eligible to participate in the study.
Female patients of child-bearing potential must agree to use a medically acceptable method of contraception at all times during the study. Pregnancy testing will be performed at the time of enrollment and as required throughout participation in the study. Male patients must agree to use a medically acceptable method of contraception at all times during the study and report a partner's pregnancy to the Investigator.
The patient's parent(s) or the patient's legally authorized representative(s) has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC).
Exclusion Criteria: Patients who meet any of the following criteria will be excluded from this study.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alexandria University Hospital | Alexandria | 21131 | Egypt | |||
| Abu El Rich Hospital, Cairo University Hospital |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Velaglucerase Alfa | Participants received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Velaglucerase Alfa | Participants received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline to 12 Months (Week 53) in Hemoglobin Concentration | Hemoglobin concentration was measured as part of the hematology panel or measured separately when the hematology panel was not scheduled. Samples were measured by a central laboratory. Baseline is the modified baseline hemoglobin concentration, the average of the values from screening, baseline, and Week 1/Day 1. A positive change from baseline indicates that hemoglobin concentration increased. | The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial). | Posted | Mean | Standard Deviation | g/dL | Baseline, Week 53 or end of study |
|
Not provided
Treatment-emergent adverse events are reported for the Safety population, defined as all participants who received at least 1 study drug infusion (full or partial).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Velaglucerase Alfa | Participants received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Inguinal hernia | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
Not provided
| ID | Term |
|---|---|
| D005776 | Gaucher Disease |
| ID | Term |
|---|---|
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
Not provided
Not provided
| ID | Term |
|---|---|
| D005962 | Glucosylceramidase |
| D056947 | Enzyme Replacement Therapy |
| ID | Term |
|---|---|
| D005959 | Glucosidases |
| D006026 | Glycoside Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Percent Change From Baseline to 12 Months (Week 51) in Normalized Liver Volume Measured Using Magnetic Resonance Imaging (MRI) | Quantitative abdominal MRI was used to measure liver volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, liver volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The liver size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in liver volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that liver volume decreased. | Baseline, Week 51 or end of study |
| Percent Change From Baseline to 12 Months (Week 51) in Normalized Spleen Volume Measured Using Magnetic Resonance Imaging (MRI) | Quantitative abdominal MRI was used to measure spleen volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, spleen volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The spleen size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in spleen volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that spleen volume decreased. | Baseline, Week 51 |
| Number of Participants With Abnormal Neurological Status During The Study | Neurological symptoms were evaluated at regular intervals during the study and assessed on an individualized basis by a limited, age- and developmental stage-appropriate neurological examination adapted to suit the status of each participant. It was preferred that each neurological examination be performed by a neurologist with experience in assessment of neurological symptoms in patients with Gaucher disease and, if possible, the same neurologist (or designee) who evaluated a given participant at baseline performed the neurological examinations scheduled for that participant during the treatment phase and at the end of study visit. | Baseline, Weeks 13, 25, 37, and 53 or end of study |
| Number of Participants Who Experienced a Treatment-Emergent Adverse Event | Adverse events (AEs) were monitored continuously throughout the study from the time the participant or participants parent/legal guardian signed the informed consent/assent (if applicable) until 30 days after the participant's last dose of study drug or at the end of study visit and/or until the event resolved or stabilized, or an outcome had been reached, whichever came first. Treatment-emergent adverse events (TEAEs) were defined as AEs which occurred on or after the time of the first infusion until 30 days after the participant's last study infusion. An infusion-related reaction is 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 study medication. | 57 weeks |
| Number of Participants Who Developed Anti-Velaglucerase Alfa Antibodies During The Study | Participants provided blood samples for measurement of anti-velaglucerase alfa antibodies in serum at baseline and approximately every 12 weeks during the treatment phase. Blood samples collected during the treatment phase were to be drawn prior to infusions. Analysis of anti-velaglucerase antibodies used a validated 3-tier immunoassay method (screening, confirmatory, and titer). | Baseline, Weeks 13, 25, 37 and 53 |
| Cairo |
| Egypt |
| Children's Hospital, Ain Shams University Hospital | Cairo | Egypt |
| KEM Hospital Research Centre | Pune | Maharashtra | India |
| Hospital La Rabta | Tunis | 1007 | Tunisia |
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Secondary | Change From Baseline to 12 Months (Week 53) in Platelet Count | Platelet count was measured at a central laboratory as part of the hematology panel. Baseline is the modified baseline platelet count, the average of the values from screening, baseline and Week 1/Day 1. A positive change from baseline indicates that platelet count increased. | The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial). | Posted | Mean | Standard Deviation | platelets (x10^9)/L | Baseline, Week 53 |
|
|
|
| Secondary | Percent Change From Baseline to 12 Months (Week 51) in Normalized Liver Volume Measured Using Magnetic Resonance Imaging (MRI) | Quantitative abdominal MRI was used to measure liver volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, liver volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The liver size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in liver volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that liver volume decreased. | The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial). | Posted | Mean | Standard Deviation | percent change | Baseline, Week 51 or end of study |
|
|
|
| Secondary | Percent Change From Baseline to 12 Months (Week 51) in Normalized Spleen Volume Measured Using Magnetic Resonance Imaging (MRI) | Quantitative abdominal MRI was used to measure spleen volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, spleen volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The spleen size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in spleen volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that spleen volume decreased. | The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial). | Posted | Mean | Standard Deviation | percent change | Baseline, Week 51 |
|
|
|
| Secondary | Number of Participants With Abnormal Neurological Status During The Study | Neurological symptoms were evaluated at regular intervals during the study and assessed on an individualized basis by a limited, age- and developmental stage-appropriate neurological examination adapted to suit the status of each participant. It was preferred that each neurological examination be performed by a neurologist with experience in assessment of neurological symptoms in patients with Gaucher disease and, if possible, the same neurologist (or designee) who evaluated a given participant at baseline performed the neurological examinations scheduled for that participant during the treatment phase and at the end of study visit. | The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial). | Posted | Number | participants | Baseline, Weeks 13, 25, 37, and 53 or end of study |
|
|
|
| Secondary | Number of Participants Who Experienced a Treatment-Emergent Adverse Event | Adverse events (AEs) were monitored continuously throughout the study from the time the participant or participants parent/legal guardian signed the informed consent/assent (if applicable) until 30 days after the participant's last dose of study drug or at the end of study visit and/or until the event resolved or stabilized, or an outcome had been reached, whichever came first. Treatment-emergent adverse events (TEAEs) were defined as AEs which occurred on or after the time of the first infusion until 30 days after the participant's last study infusion. An infusion-related reaction is 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 study medication. | The Safety Analysis population, defined as all participants who received at least 1 study drug infusion (full or partial). | Posted | Number | participants | 57 weeks |
|
|
|
| Secondary | Number of Participants Who Developed Anti-Velaglucerase Alfa Antibodies During The Study | Participants provided blood samples for measurement of anti-velaglucerase alfa antibodies in serum at baseline and approximately every 12 weeks during the treatment phase. Blood samples collected during the treatment phase were to be drawn prior to infusions. Analysis of anti-velaglucerase antibodies used a validated 3-tier immunoassay method (screening, confirmatory, and titer). | The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial). | Posted | Number | participants | Baseline, Weeks 13, 25, 37 and 53 |
|
|
|
| 1 |
| 6 |
| 6 |
| 6 |
| Anaemia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA (14.0) | Systematic Assessment |
|
| Strabismus | Eye disorders | MedDRA (14.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Inguinal hernia | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Acute tonsillitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Postprocedural cellulitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Synovial cyst | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Fine motor delay | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Gross motor delay | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Muscle spasticity | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Heat rash | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
|
| Chilblains | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
|
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D052439 | Lipid Metabolism Disorders |
| D045762 |
| Enzymes and Coenzymes |
| D057487 | Enzyme Therapy |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|
|
| Week 37 |
|
| Week 53 |
|