Trial Outcomes & Findings for A Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Gaucher Disease (NCT NCT00430625)

NCT ID: NCT00430625

Last Updated: 2021-06-29

Results Overview

Efficacy endpoint

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 25 participants
• Primary outcome timeframe: Week 53
• Results posted on: 2021-06-29

Participant Flow

Type 1 Gaucher disease patients (pts) >2 years. The first patient (pt) was enrolled in the study on 15 February 2007.

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.

Participant milestones

Measure	VPRIV® (45 U/kg, IV, Every Other Week) velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB	VPRIV® (60 U/kg, IV, Every Other Week) velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Overall Study STARTED	13	12
Overall Study COMPLETED	13	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	VPRIV® (45 U/kg, IV, Every Other Week) n=13 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB	VPRIV® (60 U/kg, IV, Every Other Week) n=12 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB	Total n=25 Participants Total of all reporting groups
Age, Categorical <=18 years	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	30.0 years FULL_RANGE 16.75 • n=5 Participants	23.5 years FULL_RANGE 11.77 • n=7 Participants	25 years FULL_RANGE 15.28 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment Paraguay	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Argentina	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Russian Federation	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Israel	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Tunisia	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Baseline Spleen volume	2.9 Percent of body weight n=5 Participants	2.8 Percent of body weight n=7 Participants	2.9 Percent of body weight n=5 Participants
Baseline hemoglobin concentration per treatment group	10.90 g/dL FULL_RANGE 1.278 • n=5 Participants	10.83 g/dL FULL_RANGE 1.272 • n=7 Participants	10.85 g/dL FULL_RANGE 1.248 • n=5 Participants
Baseline liver volume	3.50 Percent of body weight n=5 Participants	3.65 Percent of body weight n=7 Participants	3.5 Percent of body weight n=5 Participants
Baseline platelet counts per treatment group	58.00 (x10^9/L) FULL_RANGE 59.56 • n=5 Participants	66.75 (x10^9/L) FULL_RANGE 111.91 • n=7 Participants	65.5 (x10^9/L) FULL_RANGE 86.71 • n=5 Participants

PRIMARY outcome

Timeframe: Week 53

Population: 12 patients in the 60 U/kg group were analyzed for efficacy in the intent to treat (ITT) population.

Efficacy endpoint

Outcome measures

Measure	VPRIV® (60 U/kg, IV, Every Other Week) n=12 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB	VPRIV® (60 U/kg, IV, Every Other Week) velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Change From Baseline to 12 Months in Hemoglobin Concentration for the 60 U/kg Treatment Group.	2.429 g/dL Interval 1.717 to 3.141	—

SECONDARY outcome

Timeframe: Week 53

Population: 13 patients in the 45 U/kg group were analyzed for efficacy in the intent to treat (ITT) population.

Outcome measures

Measure	VPRIV® (60 U/kg, IV, Every Other Week) n=13 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB	VPRIV® (60 U/kg, IV, Every Other Week) velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Change From Baseline to 12 Months in Hemoglobin Concentration in 45 U/kg Treatment Group	2.438 (g/dL) Interval 1.488 to 3.389	—

SECONDARY outcome

Timeframe: Week 53

Population: 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.

intent to treat (ITT) Population

Outcome measures

Measure	VPRIV® (60 U/kg, IV, Every Other Week) n=13 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB	VPRIV® (60 U/kg, IV, Every Other Week) n=12 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Change From Baseline to 12 Months in Platelet Counts for Each Treatment Group.	40.92 x10^9/L Interval 11.2 to 70.64	50.88 x10^9/L Interval 23.97 to 77.78

SECONDARY outcome

Timeframe: Week 51

Population: 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.

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

Outcome measures

Measure	VPRIV® (60 U/kg, IV, Every Other Week) n=13 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB	VPRIV® (60 U/kg, IV, Every Other Week) n=12 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Change From Baseline to 12 Months in Normalized Liver Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI)	-0.30 Percent body weight Interval -0.92 to 0.32	-0.84 Percent body weight Interval -1.58 to -0.11

SECONDARY outcome

Timeframe: Week 51

Population: 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.

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

Outcome measures

Measure	VPRIV® (60 U/kg, IV, Every Other Week) n=13 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB	VPRIV® (60 U/kg, IV, Every Other Week) n=12 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Change From Baseline to 12 Months in Normalized Spleen Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI))	-1.87 Percent body weight Interval -3.17 to -0.57	-1.92 Percent body weight Interval -3.04 to -0.79

SECONDARY outcome

Timeframe: Week 53

Population: 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.

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.

Outcome measures

Measure	VPRIV® (60 U/kg, IV, Every Other Week) n=2 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB	VPRIV® (60 U/kg, IV, Every Other Week) n=7 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Percent Change From Baseline to 12 Months in Plasma Chitotriosidase for Each Treatment Group	-61.16 Percent 7.768	-69.65 Percent 17.65

SECONDARY outcome

Timeframe: Week 53

Population: 12 patients in the 60 U/kg group and 13 patients in the 45 U/kg group were analyzed.

Outcome measures

Measure	VPRIV® (60 U/kg, IV, Every Other Week) n=13 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB	VPRIV® (60 U/kg, IV, Every Other Week) n=12 Participants velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Percent Change From Baseline to 12 Months in Chemokine (C-C Motif) Ligand 18 (CCL18)	-46.76 Percent 7.623	-66.02 Percent 5.358

Adverse Events

VPRIV® (45 U/kg, IV, Every Other Week)

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

VPRIV® (60 U/kg, IV, Every Other Week)

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	VPRIV® (45 U/kg, IV, Every Other Week) n=13 participants at risk velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB	VPRIV® (60 U/kg, IV, Every Other Week) n=12 participants at risk velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Nervous system disorders Grand mal convulsion	0.00% 0/13 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.

Other adverse events

Measure	VPRIV® (45 U/kg, IV, Every Other Week) n=13 participants at risk velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB	VPRIV® (60 U/kg, IV, Every Other Week) n=12 participants at risk velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB
Infections and infestations Tinea cruris	0.00% 0/13 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.
Blood and lymphatic system disorders Thrombocytopenia	7.7% 1/13 • Number of events 1 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.
Metabolism and nutrition disorders Hyperproteinaemia	0.00% 0/13 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.
Nervous system disorders Headache	15.4% 2/13 • Number of events 2 • 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 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.	16.7% 2/12 • Number of events 2 • 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 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.
Nervous system disorders Dizziness	7.7% 1/13 • Number of events 1 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.
Nervous system disorders Somnolence	7.7% 1/13 • Number of events 1 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.
Eye disorders Eyelid oedema	7.7% 1/13 • Number of events 1 • 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 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.	0.00% 0/12 • 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 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.
Cardiac disorders Tachycardia	7.7% 1/13 • Number of events 1 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.
Vascular disorders Hypertension	7.7% 1/13 • Number of events 1 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.
Vascular disorders Hypotension	7.7% 1/13 • Number of events 1 • 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 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.	16.7% 2/12 • Number of events 2 • 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 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.
Respiratory, thoracic and mediastinal disorders Productive cough	7.7% 1/13 • Number of events 1 • 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 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.	0.00% 0/12 • 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 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.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.7% 1/13 • Number of events 1 • 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 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.	0.00% 0/12 • 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 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.
Gastrointestinal disorders Diarrhoea	0.00% 0/13 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.
Gastrointestinal disorders Gingivitis	0.00% 0/13 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.
Skin and subcutaneous tissue disorders Petechiae	15.4% 2/13 • Number of events 2 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.
Skin and subcutaneous tissue disorders Purpura	7.7% 1/13 • Number of events 1 • 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 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.	0.00% 0/12 • 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 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.
Musculoskeletal and connective tissue disorders Arthralgia	15.4% 2/13 • Number of events 2 • 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 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.	0.00% 0/12 • 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 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.
Musculoskeletal and connective tissue disorders Back pain	15.4% 2/13 • Number of events 2 • 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 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.	0.00% 0/12 • 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 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.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/13 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.
Musculoskeletal and connective tissue disorders Muscle spasms	7.7% 1/13 • Number of events 1 • 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 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.	0.00% 0/12 • 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 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.
General disorders Asthenia	7.7% 1/13 • Number of events 1 • 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 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.	0.00% 0/12 • 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 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.
General disorders Feeling cold	7.7% 1/13 • Number of events 1 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.
General disorders Chills	0.00% 0/13 • 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 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.	8.3% 1/12 • Number of events 1 • 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 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.
Injury, poisoning and procedural complications Injury	7.7% 1/13 • Number of events 1 • 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 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.	0.00% 0/12 • 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 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.

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER