Trial Outcomes & Findings for Multicenter Extension Study of Velaglucerase Alfa in Japanese Patients With Gaucher Disease (NCT NCT01842841)
NCT ID: NCT01842841
Last Updated: 2021-06-14
Results Overview
An AE was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered related to investigational product. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An infusion-related AE was defined as an AE that started either during or within 12 hours after the start of the infusion and that was judged as possibly or probably related to investigational product.
COMPLETED
PHASE3
5 participants
From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
2021-06-14
Participant Flow
Participants from study HGT-GCB-087 (NCT01614574) were enrolled in this study except one participant who was not enrolled due to personal reasons.
Participant milestones
| Measure |
Velaglucerase Alfa (VPRIV®)
Velaglucerase alfa (VPRIV®) 15 to 60 units per kilogram (U/kg), every other week (EOW) administered as an intravenous (IV) infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Overall Study
STARTED
|
5
|
|
Overall Study
COMPLETED
|
5
|
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Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Multicenter Extension Study of Velaglucerase Alfa in Japanese Patients With Gaucher Disease
Baseline characteristics by cohort
| Measure |
Velaglucerase Alfa (VPRIV®)
n=5 Participants
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Age, Continuous
|
22.20 years
STANDARD_DEVIATION 11.946 • n=39 Participants
|
|
Sex: Female, Male
Female
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1 Participants
n=39 Participants
|
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Sex: Female, Male
Male
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4 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)Population: Safety population.
An AE was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered related to investigational product. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An infusion-related AE was defined as an AE that started either during or within 12 hours after the start of the infusion and that was judged as possibly or probably related to investigational product.
Outcome measures
| Measure |
Velaglucerase Alfa (VPRIV®)
n=5 Participants
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Number of Participants With Drug-related Adverse Events (AEs), Infusion-related AEs, and Serious AEs (SAEs)
Study drug-related AEs
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2 participants
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Number of Participants With Drug-related Adverse Events (AEs), Infusion-related AEs, and Serious AEs (SAEs)
Infusion-related AEs
|
0 participants
|
|
Number of Participants With Drug-related Adverse Events (AEs), Infusion-related AEs, and Serious AEs (SAEs)
Serious AEs
|
2 participants
|
PRIMARY outcome
Timeframe: From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)Population: Safety population.
Outcome measures
| Measure |
Velaglucerase Alfa (VPRIV®)
n=5 Participants
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Number of Participants Using Concomitant Medication
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5 participants
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PRIMARY outcome
Timeframe: From Week 65 until the end of study (Week 155)Population: Safety population.
Laboratory test results were considered abnormal and clinically significant at the discretion of the investigator.
Outcome measures
| Measure |
Velaglucerase Alfa (VPRIV®)
n=5 Participants
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Number of Participants With Abnormal and Clinically Significant Laboratory Test Results
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1 participants
|
PRIMARY outcome
Timeframe: From Week 65 until the end of study (Week 155)Population: Safety population.
Serum samples were collected for all participants for determination of anti-velaglucerase alfa antibodies every 12 weeks.
Outcome measures
| Measure |
Velaglucerase Alfa (VPRIV®)
n=5 Participants
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Number of Participants With Positive Anti-Velaglucerase Alfa Antibodies
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0 participants
|
SECONDARY outcome
Timeframe: Baseline, Week 101Population: Safety population
Baseline was the modified baseline hemoglobin concentration, the average of the values from screening, baseline, and Week 1 Day 1 from Study HGT-GCB-087 (NCT01614574).
Outcome measures
| Measure |
Velaglucerase Alfa (VPRIV®)
n=5 Participants
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Change From Baseline in Hemoglobin Concentration at Week 101
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0.22 gram per deciliter (g/dL)
Standard Deviation 0.817
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SECONDARY outcome
Timeframe: Baseline, Week 101Population: Safety population
Baseline was the modified baseline platelet count, the average of the values from screening, baseline, and Week 1 Day 1 from Study HGT-GCB-087 (NCT01614574).
Outcome measures
| Measure |
Velaglucerase Alfa (VPRIV®)
n=5 Participants
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Change From Baseline in Platelet Count at Week 101
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9.8 *10^9 platelets per liter
Standard Deviation 13.14
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SECONDARY outcome
Timeframe: Baseline, Week 103Population: Safety population
Liver volume was measured using magnetic resonance imaging (MRI). Liver volume measurements were normalized to the percentage of body weight. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Outcome measures
| Measure |
Velaglucerase Alfa (VPRIV®)
n=5 Participants
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Change From Baseline in Liver Volume Normalized to Body Weight at Week 103
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0.01 Percentage of body weight
Standard Deviation 0.207
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SECONDARY outcome
Timeframe: Baseline, Week 103Population: Safety population
Spleen volume was measured using MRI. Spleen volume measurements were normalized to the percentage of body weight. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Outcome measures
| Measure |
Velaglucerase Alfa (VPRIV®)
n=5 Participants
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Change From Baseline in Spleen Volume Normalized to Body Weight at Week 103
|
0.04 Percentage of body weight
Standard Deviation 0.089
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SECONDARY outcome
Timeframe: Baseline, Week 103Population: Data was not reported as there were lesser than (\<) 50% of participants with evaluable data.
BMD was measured by dual energy x-ray absorptiometry (DXA) for lumbar spine and femurs. To ensure standardization and allow for comparisons of BMD, results were converted to standardized Z-scores (matched for age and gender). Z-scores express the BMD as the number of standard deviations (SDs) above or below the average BMD of a healthy participant of the same age and gender. Statistical analysis plan only required summarization if greater than (\>) 50 percent (%) of participants had evaluable data. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 103Population: Data was not reported as there were \<50% of participants with evaluable data.
BMD was measured by DXA for lumbar spine and femurs. To ensure standardization and allow for comparisons of BMD, results were converted to standardized T-scores; normal values were used from databases from Hologic based on standard criteria. T-scores are the number of SDs above or below the average for a young adult at peak BMD. Statistical analysis plan only required summarization if \>50% of participants had evaluable data. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 103Population: Safety population.
BMB Score was measured using MRI, range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0-16 points. A higher BMB score signified more severe bone marrow involvement. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Outcome measures
| Measure |
Velaglucerase Alfa (VPRIV®)
n=5 Participants
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Change From Baseline in Bone Marrow Burden (BMB) Score at Week 103
Lumbar spine scores
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-1.2 units on a scale
Standard Deviation 1.79
|
|
Change From Baseline in Bone Marrow Burden (BMB) Score at Week 103
Femur scores
|
0.0 units on a scale
Standard Deviation 2.12
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Change From Baseline in Bone Marrow Burden (BMB) Score at Week 103
Total scores
|
-1.2 units on a scale
Standard Deviation 2.95
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SECONDARY outcome
Timeframe: Baseline, Week 101Population: Data was not reported as there was \<50% of participants had evaluable data.
The Z-score, or Standard Deviation Score, is a measure of number of SDs above or below the average BMD of a healthy participant of the same age and gender. World Health Organization 2007 growth reference data were used for Z-score calculation. Statistical analysis plan only required summarization if \>50% of participants had evaluable data. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 103Population: Data was not reported as there was \<50% of participants had evaluable data.
Skeletal age was measured via radiography (X-ray) of the left hand and wrist by the method of Greulich and Pyle. The Z-score, or Standard Deviation Score, is a measure of number of SDs above or below the average BMD of a healthy participant of the same age and gender. Statistical analysis plan only required summarization if \>50% of participants had evaluable data. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 101Population: Safety population. Number of participants analyzed signifies participants who were not deficient at baseline in chitotriosidase activity or who did not have a 24 base pair duplication in either copy of the chitotriosidase gene.
Plasma chitotriosidase activity levels were measured using an enzymatic assay with 4-methylumbelliferyl-deoxychitobiose as a substrate. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Outcome measures
| Measure |
Velaglucerase Alfa (VPRIV®)
n=2 Participants
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
|
Change From Baseline in Plasma Chitotriosidase Levels at Week 101
|
-181.0 nanomole/milliliter/hour (nmol/mL/h)
Standard Deviation 268.70
|
SECONDARY outcome
Timeframe: Baseline, Week 103Population: Safety population. Number of participants analyzed signifies participants evaluable for this outcome.
Neurological status was considered normal or abnormal based on investigator's discretion. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Outcome measures
| Measure |
Velaglucerase Alfa (VPRIV®)
n=3 Participants
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Number of Participants With Change From Baseline in Neurological Status at Week 103
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0 participants
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SECONDARY outcome
Timeframe: Baseline, Week 101Population: Safety population
Plasma CCL18 concentrations were measured using a time-resolved fluorescence assay. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Outcome measures
| Measure |
Velaglucerase Alfa (VPRIV®)
n=5 Participants
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Change From Baseline in Chemokine [C-C Motif] Ligand 18 (CCL18) Levels at Week 101
|
-11.4 nanogram per milliliter (ng/mL)
Standard Deviation 50.97
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Adverse Events
Velaglucerase Alfa (VPRIV®)
Serious adverse events
| Measure |
Velaglucerase Alfa (VPRIV®)
n=5 participants at risk
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
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|---|---|
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Ear and labyrinth disorders
Hypoacusis
|
20.0%
1/5 • Number of events 2 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Eye disorders
Retinal detachment
|
20.0%
1/5 • Number of events 2 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Eye disorders
Vitreous opacities
|
20.0%
1/5 • Number of events 2 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
Other adverse events
| Measure |
Velaglucerase Alfa (VPRIV®)
n=5 participants at risk
Velaglucerase alfa (VPRIV®) 15 to 60 U/kg, EOW, administered as an IV infusion over 60 minutes from Week 53 (2 weeks after the last infusion \[Week 51\] in Study HGT-GCB-087 \[NCT01614574\]) to Week 155.
|
|---|---|
|
Ear and labyrinth disorders
Hypoacusis
|
20.0%
1/5 • Number of events 2 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Eye disorders
Retinal detachment
|
20.0%
1/5 • Number of events 2 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Eye disorders
Vitreous opacities
|
20.0%
1/5 • Number of events 2 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
40.0%
2/5 • Number of events 2 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Gastrointestinal disorders
Constipation
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Gastrointestinal disorders
Enteritis
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
General disorders
Chest pain
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Infections and infestations
Adenoiditis
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Infections and infestations
Gastroenteritis
|
40.0%
2/5 • Number of events 2 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Infections and infestations
Hordeolum
|
40.0%
2/5 • Number of events 2 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Infections and infestations
Nasopharyngitis
|
40.0%
2/5 • Number of events 7 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Infections and infestations
Otitis media acute
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Infections and infestations
Subcutaneous abscess
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Infections and infestations
Upper respiratory tract infection
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Injury, poisoning and procedural complications
Concussion
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Injury, poisoning and procedural complications
Contusion
|
40.0%
2/5 • Number of events 3 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Injury, poisoning and procedural complications
Excoriation
|
40.0%
2/5 • Number of events 2 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Injury, poisoning and procedural complications
Fall
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Injury, poisoning and procedural complications
Heat stroke
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Injury, poisoning and procedural complications
Wound
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Investigations
Blood creatine phosphokinase increased
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Investigations
C-Reactive protein increased
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Investigations
Intraocular pressure increased
|
20.0%
1/5 • Number of events 2 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Musculoskeletal and connective tissue disorders
Muscle fatigue
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Musculoskeletal and connective tissue disorders
Trigger finger
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Nervous system disorders
Headache
|
60.0%
3/5 • Number of events 4 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Psychiatric disorders
Sleep disorder
|
20.0%
1/5 • Number of events 2 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Psychiatric disorders
Somatoform disorder
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Skin and subcutaneous tissue disorders
Eczema
|
20.0%
1/5 • Number of events 1 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
20.0%
1/5 • Number of events 2 • From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER