Clinical Trial: Efficacy and Safety Study of Velaglucerase Alfa in Children and Adolescents With Type 3 Gaucher Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multi-center, Open-label, Efficacy and Safety Study of Velaglucerase Alfa Enzyme Replacement Therapy in Children and Adolescents With Type 3 Gaucher Disease

Brief Summary:

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.

Detailed Summary:

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.

Current Primary Outcome: Change From Baseline to 12 Months (Week 53) in Hemoglobin Concentration [ Time Frame: Baseline, Week 53 or end of study ]

Original Primary Outcome: Change from Baseline to 12 months in hemoglobin concentration [ Time Frame: End of study-12 months ]

Current Secondary Outcome:

• Change From Baseline to 12 Months (Week 53) in Platelet Count [ Time Frame: Baseline, Week 53 ]
  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.
• Percent Change From Baseline to 12 Months (Week 51) in Normalized Liver Volume Measured Using Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline, Week 51 or end of study ]
  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.
• Percent Change From Baseline to 12 Months (Week 51) in Normalized Spleen Volume Measured Using Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline, Week 51 ]
  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.
• Number of Participants With Abnormal Neurological Status During The Study [ Time Frame: Baseline, Weeks 13, 25, 37, and 53 or end of 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.
• Number of Participants Who Experienced a Treatment-Emergent Adverse Event [ Time Frame: 57 weeks ]
  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.
• Number of Participants Who Developed Anti-Velaglucerase Alfa Antibodies During The Study [ Time Frame: Baseline, Weeks 13, 25, 37 and 53 ]
  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).

Original Secondary Outcome:

• Change from Baseline to 12 months in platelet count [ Time Frame: End of study-12 months ]
• Change from Baseline to 12 months in normalized liver volumes measured using magnetic resonance imaging (MRI) [ Time Frame: End of study-12 months ]
• Change from Baseline to 12 months in normalized spleen volumes measured using magnetic resonance imaging (MRI) [ Time Frame: End of study-12 months ]
• Change from Baseline to 12 months in neurological symptoms [ Time Frame: End of study-12 months ]
• Safety Assessments [ Time Frame: Study duration-12 months ]
  Adverse events (AEs) and infusion-related AEs, serious adverse events (SAEs), clinical laboratory values, urinalysis, vital signs, 12-lead electrocardiogram (ECG) recordings, physical examination, and anti-velaglucerase alfa antibody formation

Dates:
Date Received: September 10, 2012
Date Started: September 2012
Date Completion:
Last Updated: October 1, 2015
Last Verified: October 2015