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A Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Gaucher Disease

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ClinicalTrials.gov Identifier: NCT00430625
Recruitment Status : Completed
First Posted : February 2, 2007
Results First Posted : September 10, 2010
Last Update Posted : March 17, 2014
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Gaucher Disease, Type 1
Intervention Biological: VPRIV ®,
Enrollment 25

Recruitment Details Type 1 Gaucher disease patients (pts) >2 years. The first patient (pt) consented to participate in the study on 11 January 2007 and the last patient enrolled on 04 April 2008.
Pre-assignment Details Gaucher disease-related anemia and at least 1 of the following: moderate splenomegaly, thrombocytopenia or palpable enlarged liver. Patients were not to have received any treatment for Gaucher disease within 30 months of study entry. Patients randomized to receive VPRIV®(45 or 60 U/kg)every other week by intravenous (IV) infusion.
Arm/Group Title VPRIV® (45 U/kg, IV, Every Other Week) VPRIV® (60 U/kg, IV, Every Other Week)
Hide Arm/Group Description velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Period Title: Overall Study
Started 13 12
Completed 13 12
Not Completed 0 0
Arm/Group Title VPRIV® (45 U/kg, IV, Every Other Week) VPRIV® (60 U/kg, IV, Every Other Week) Total
Hide Arm/Group Description velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB Total of all reporting groups
Overall Number of Baseline Participants 13 12 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 12 participants 25 participants
<=18 years
3
  23.1%
4
  33.3%
7
  28.0%
Between 18 and 65 years
10
  76.9%
8
  66.7%
18
  72.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 13 participants 12 participants 25 participants
30.0
(6 to 62)
23.5
(4 to 42)
25
(4 to 62)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 12 participants 25 participants
Female
5
  38.5%
5
  41.7%
10
  40.0%
Male
8
  61.5%
7
  58.3%
15
  60.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 12 participants 25 participants
Paraguay 6 5 11
Argentina 1 0 1
Russian Federation 3 0 3
Israel 1 6 7
Tunisia 2 1 3
Baseline Spleen volume   [1] 
Median (Full Range)
Unit of measure:  Percent of body weight
Number Analyzed 13 participants 12 participants 25 participants
2.9
(0.5 to 13.0)
2.8
(0.4 to 7.4)
2.9
(0.4 to 13.0)
[1]
Measure Description: Normal spleen volume is defined as 0.2 percentage of body weight.
Baseline hemoglobin concentration per treatment group   [1] 
Median (Full Range)
Unit of measure:  g/dL
Number Analyzed 13 participants 12 participants 25 participants
10.90
(8.45 to 12.85)
10.83
(7.05 to 12.25)
10.85
(7.05 to 12.85)
[1]
Measure Description: Modified baseline used for analysis (defined as average of screening and baseline values)
Baseline liver volume   [1] 
Median (Full Range)
Unit of measure:  Percent of body weight
Number Analyzed 13 participants 12 participants 25 participants
3.50
(2.3 to 7.2)
3.65
(2.4 to 8.0)
3.5
(2.3 to 8.0)
[1]
Measure Description: Normal liver volume is defined as 2.5 percent of body weight.
Baseline platelet counts per treatment group   [1] 
Median (Full Range)
Unit of measure:  (x10^9/L)
Number Analyzed 13 participants 12 participants 25 participants
58.00
(13 to 264)
66.75
(47 to 438)
65.5
(13 to 438)
[1]
Measure Description: Modified baseline used for analysis (defined as average of screening and baseline values)
1.Primary Outcome
Title Change From Baseline to 12 Months in Hemoglobin Concentration for the 60 U/kg Treatment Group.
Hide Description Efficacy endpoint
Time Frame Week 53
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
12 patients in the 60 U/kg group were analyzed for efficacy in the intent to treat (ITT) population.
Arm/Group Title VPRIV® (60 U/kg, IV, Every Other Week)
Hide Arm/Group Description:
velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Overall Number of Participants Analyzed 12
Mean (95% Confidence Interval)
Unit of Measure: g/dL
2.429
(1.717 to 3.141)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection VPRIV® (60 U/kg, IV, Every Other Week)
Comments Primary endpoint was based solely on the 60 U/kg treatment arm
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method paired t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.429
Confidence Interval (2-Sided) 95%
1.717 to 3.141
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.324
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to 12 Months in Hemoglobin Concentration in 45 U/kg Treatment Group
Hide Description [Not Specified]
Time Frame Week 53
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
13 patients in the 45 U/kg group were analyzed for efficacy in the intent to treat (ITT) population.
Arm/Group Title VPRIV® (45 U/kg, IV, Every Other Week)
Hide Arm/Group Description:
velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Overall Number of Participants Analyzed 13
Mean (95% Confidence Interval)
Unit of Measure: (g/dL)
2.438
(1.488 to 3.389)
3.Secondary Outcome
Title Change From Baseline to 12 Months in Platelet Counts for Each Treatment Group.
Hide Description intent to treat (ITT) Population
Time Frame Week 53
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
12 patients in the 60 U/kg group and 13 patients in the 45 U/kg group were analyzed for efficacy in the intent to treat (ITT) population.
Arm/Group Title VPRIV® (45 U/kg, IV, Every Other Week) VPRIV® (60 U/kg, IV, Every Other Week)
Hide Arm/Group Description:
velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Overall Number of Participants Analyzed 13 12
Mean (95% Confidence Interval)
Unit of Measure: x10^9/L
40.92
(11.20 to 70.64)
50.88
(23.97 to 77.78)
4.Secondary Outcome
Title Change From Baseline to 12 Months in Normalized Liver Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI)
Hide Description Liver Volume has been normalized for percentage of body weight for each treatment arm. Liver size relative to body weight = (Liver volume [cc]/Body weight [kg])*100
Time Frame Week 51
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
12 patients in the 60 U/kg group and 13 patients in the 45 U/kg group were analyzed for efficacy in the intent to treat (ITT) population.
Arm/Group Title VPRIV® (45 U/kg, IV, Every Other Week) VPRIV® (60 U/kg, IV, Every Other Week)
Hide Arm/Group Description:
velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Overall Number of Participants Analyzed 13 12
Mean (95% Confidence Interval)
Unit of Measure: Percent body weight
-0.30
(-0.92 to 0.32)
-0.84
(-1.58 to -0.11)
5.Secondary Outcome
Title Change From Baseline to 12 Months in Normalized Spleen Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI))
Hide Description 12 patients in the 60 U/kg group and 13 patients in the 45 U/kg group were analyzed for efficacy in the intent to treat (ITT) population. Spleen Volume has been normalized for percent of body weight for each treatment arm. Spleen size relative to body weight = (Spleen volume [cc]/Body weight [kg])*100
Time Frame Week 51
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
12 patients in the 60 U/kg group and 13 patients in the 45 U/kg group were analyzed for efficacy in the intent to treat (ITT) population.
Arm/Group Title VPRIV® (45 U/kg, IV, Every Other Week) VPRIV® (60 U/kg, IV, Every Other Week)
Hide Arm/Group Description:
velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Overall Number of Participants Analyzed 13 12
Mean (95% Confidence Interval)
Unit of Measure: Percent body weight
-1.87
(-3.17 to -0.57)
-1.92
(-3.04 to -0.79)
6.Secondary Outcome
Title Percent Change From Baseline to 12 Months in Plasma Chitotriosidase for Each Treatment Group
Hide Description Percent Change from Baseline to Weeks 53 by Randomized velaglucerase alfa Treatment Group - Subset of intent to treat (ITT) Population who were wild type homozygous for chitotriosidase.
Time Frame Week 53
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
2 patients in the 60 U/kg group and 7 patients in the 45 U/kg group who were wild type for the chitotriosidase mutation were analyzed; remaining patients were deficient in chitotriosidase activity.
Arm/Group Title VPRIV® (45 U/kg, IV, Every Other Week) VPRIV® (60 U/kg, IV, Every Other Week)
Hide Arm/Group Description:
velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Overall Number of Participants Analyzed 2 7
Measure Type: Number
Unit of Measure: Percent
-61.16 -69.65
7.Secondary Outcome
Title Percent Change From Baseline to 12 Months in Chemokine (C-C Motif) Ligand 18 (CCL18)
Hide Description [Not Specified]
Time Frame Week 53
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
12 patients in the 60 U/kg group and 13 patients in the 45 U/kg group were analyzed.
Arm/Group Title VPRIV® (45 U/kg, IV, Every Other Week) VPRIV® (60 U/kg, IV, Every Other Week)
Hide Arm/Group Description:
velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Overall Number of Participants Analyzed 13 12
Measure Type: Number
Unit of Measure: Percent
-46.76 -66.02
Time Frame Adverse events were monitored either from time of informed consent/assent (Amendment 1) or from the first infusion (original protocol) through 30 days after the last infusion (Week 53).
Adverse Event Reporting Description Adverse events may have been discovered through observation/examination of the patient, questioning of the patient or complaint by the patient. Adverse Events could have included unexpected laboratory values that became significantly out of range. Other adverse events were determined to be possibly/probably related to VPRIV by the Investigator.
 
Arm/Group Title VPRIV® (45 U/kg, IV, Every Other Week) VPRIV® (60 U/kg, IV, Every Other Week)
Hide Arm/Group Description velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
All-Cause Mortality
VPRIV® (45 U/kg, IV, Every Other Week) VPRIV® (60 U/kg, IV, Every Other Week)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
VPRIV® (45 U/kg, IV, Every Other Week) VPRIV® (60 U/kg, IV, Every Other Week)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/13 (0.00%)      1/12 (8.33%)    
Nervous system disorders     
Grand mal convulsion  1 [1]  0/13 (0.00%)  0 1/12 (8.33%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.0)
[1]
Considered not related by investigator.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
VPRIV® (45 U/kg, IV, Every Other Week) VPRIV® (60 U/kg, IV, Every Other Week)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/13 (69.23%)      6/12 (50.00%)    
Blood and lymphatic system disorders     
Thrombocytopenia  1  1/13 (7.69%)  1 1/12 (8.33%)  1
Cardiac disorders     
Tachycardia  1  1/13 (7.69%)  1 1/12 (8.33%)  1
Eye disorders     
Eyelid oedema  1  1/13 (7.69%)  1 0/12 (0.00%)  0
Gastrointestinal disorders     
Diarrhoea  1  0/13 (0.00%)  0 1/12 (8.33%)  1
Gingivitis  1  0/13 (0.00%)  0 1/12 (8.33%)  1
General disorders     
Asthenia  1  1/13 (7.69%)  1 0/12 (0.00%)  0
Feeling cold  1  1/13 (7.69%)  1 1/12 (8.33%)  1
Chills  1  0/13 (0.00%)  0 1/12 (8.33%)  1
Infections and infestations     
Tinea cruris  1  0/13 (0.00%)  0 1/12 (8.33%)  1
Injury, poisoning and procedural complications     
Injury  1  1/13 (7.69%)  1 0/12 (0.00%)  0
Metabolism and nutrition disorders     
Hyperproteinaemia  1  0/13 (0.00%)  0 1/12 (8.33%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  2/13 (15.38%)  2 0/12 (0.00%)  0
Back pain  1  2/13 (15.38%)  2 0/12 (0.00%)  0
Bone pain  1  0/13 (0.00%)  0 1/12 (8.33%)  1
Muscle spasms  1  1/13 (7.69%)  1 0/12 (0.00%)  0
Nervous system disorders     
Headache  1  2/13 (15.38%)  2 2/12 (16.67%)  2
Dizziness  1  1/13 (7.69%)  1 1/12 (8.33%)  1
Somnolence  1  1/13 (7.69%)  1 1/12 (8.33%)  1
Respiratory, thoracic and mediastinal disorders     
Productive cough  1  1/13 (7.69%)  1 0/12 (0.00%)  0
Rhinorrhoea  1  1/13 (7.69%)  1 0/12 (0.00%)  0
Skin and subcutaneous tissue disorders     
Petechiae  1  2/13 (15.38%)  2 1/12 (8.33%)  1
Purpura  1  1/13 (7.69%)  1 0/12 (0.00%)  0
Vascular disorders     
Hypertension  1  1/13 (7.69%)  1 1/12 (8.33%)  1
Hypotension  1  1/13 (7.69%)  1 2/12 (16.67%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.0)
Due to small sample sizes no conclusions could be drawn on Quality of life (QOL).
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Shire’s agreements with investigators vary. All agreements provide Shire the right to embargo communications regarding trial results prior to public release for a period ≤180 days from the time submitted to Shire for review. Shire does not prohibit publication, but can require the removal of confidential information (excluding trial results) and can request postponement of a single-center publication until after disclosure of the trial’s multi-center publication.
Results Point of Contact
Name/Title: Tiffany Crump
Organization: Shire Human Genetic Therapies (Shire HGT)
Phone: 484-595-8850
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00430625     History of Changes
Other Study ID Numbers: TKT032
First Submitted: February 1, 2007
First Posted: February 2, 2007
Results First Submitted: June 3, 2010
Results First Posted: September 10, 2010
Last Update Posted: March 17, 2014