Trial Outcomes & Findings for Study of GA-GCB Enzyme Replacement Therapy in Type 1 Gaucher Disease Patients Previously Treated With Imiglucerase (NCT NCT00478647)
NCT ID: NCT00478647
Last Updated: 2021-06-10
Results Overview
Safety was assessed throughout the study by assessments including adverse events, concomitant medication use, and vital signs. Additional safety assessments, including 12-lead ECGs, physical examinations, clinical laboratory tests and determination of the presence of anti-velaglucerase alfa antibodies. Refer to Adverse event section for further details.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
40 participants
Primary outcome timeframe
Week 53
Results posted on
2021-06-10
Participant Flow
The first participant was enrolled on 25 July 2007 and the last participant completed on 26 June 2009. Participants received the same dose of velaglucerase alfa (GA-GCB) as their previous dose of imiglucerase (range- \</= 60 Unit per kilogram (U/kg) - \>/=15 U/kg) every other week via intravenous infusion.
Participant at least 2 years old with documented diagnosis of type 1 Gaucher disease.Consistent treatment(every other week at a dose ≤/= 60 U/kg and ≥/= 15 U/kg) with imiglucerase for a minimum of 30 consecutive months;same dose during the 6 months prior to study enrollment.Minor dosing interval variance was allowed per standard clinical practice.
Participant milestones
| Measure |
GA-GCB (Velaglucerase Alfa)
15-60 U/kg, every other week via intravenous infusion
|
|---|---|
|
Overall Study
STARTED
|
40
|
|
Overall Study
COMPLETED
|
38
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
GA-GCB (Velaglucerase Alfa)
15-60 U/kg, every other week via intravenous infusion
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Study of GA-GCB Enzyme Replacement Therapy in Type 1 Gaucher Disease Patients Previously Treated With Imiglucerase
Baseline characteristics by cohort
| Measure |
GA-GCB (Velaglucerase Alfa)
n=40 Participants
15-60 U/kg, every other week via intravenous infusion
|
|---|---|
|
Age, Categorical
<=18 years
|
9 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
27 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=5 Participants
|
|
Age, Continuous
|
35.6 years
STANDARD_DEVIATION 18.37 • n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
22 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
3 Participants
n=5 Participants
|
|
Baseline hemoglobin concentration
|
13.775 gram per deciliter (g/dL)
n=5 Participants
|
|
Baseline liver volume
|
1.90 Percent (%) body weight
n=5 Participants
|
|
Baseline platelet count
|
162.00 10^9 per liter (10^9/L)
n=5 Participants
|
|
Baseline spleen volume
|
0.50 Percent (%) body weight
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 53Population: Safety population included subjects who have received at least 1 full or partial dose of study drug.
Safety was assessed throughout the study by assessments including adverse events, concomitant medication use, and vital signs. Additional safety assessments, including 12-lead ECGs, physical examinations, clinical laboratory tests and determination of the presence of anti-velaglucerase alfa antibodies. Refer to Adverse event section for further details.
Outcome measures
| Measure |
GA-GCB (Velaglucerase Alfa)
n=40 Participants
15-60 U/kg, every other week via intravenous infusion
|
|---|---|
|
Participants Who Experienced at Least One Adverse Event
|
34 participants
|
SECONDARY outcome
Timeframe: Week 53Population: ITT population.
Outcome measures
| Measure |
GA-GCB (Velaglucerase Alfa)
n=40 Participants
15-60 U/kg, every other week via intravenous infusion
|
|---|---|
|
Change From Baseline to Week 53 in Hemoglobin Concentration
|
-0.101 g/dL
Interval -0.272 to 0.07
|
SECONDARY outcome
Timeframe: Week 53Population: ITT population.
Outcome measures
| Measure |
GA-GCB (Velaglucerase Alfa)
n=40 Participants
15-60 U/kg, every other week via intravenous infusion
|
|---|---|
|
Percent Change From Baseline to Week 53 in Platelet Count
|
7.04 percent (%) change
Interval 0.54 to 13.53
|
SECONDARY outcome
Timeframe: Week 51Population: ITT population.
Liver volume has been normalized for percentage (%) of body weight. Liver size relative to body weight= (Liver volume \[cc\]/Body weight \[kg\])\*100
Outcome measures
| Measure |
GA-GCB (Velaglucerase Alfa)
n=40 Participants
15-60 U/kg, every other week via intravenous infusion
|
|---|---|
|
Percent Change From Baseline to Week 51 in Normalized Liver Volume
|
-0.03 Percent (%) change
Interval -2.62 to 2.56
|
SECONDARY outcome
Timeframe: Week 51Population: ITT population. Four splenectomized participants were excluded.
Spleen volume has been normalized for percentage (%) of body weight. Spleen size relative to body weight= (Spleen volume \[cc\]/Body weight \[kg\])\*100
Outcome measures
| Measure |
GA-GCB (Velaglucerase Alfa)
n=36 Participants
15-60 U/kg, every other week via intravenous infusion
|
|---|---|
|
Percent Change From Baseline to Week 51 in Normalized Spleen Volume
|
-5.56 Percent (%) change
Interval -10.77 to -0.35
|
Adverse Events
GA-GCB (Velaglucerase Alfa)
Serious events: 4 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
GA-GCB (Velaglucerase Alfa)
n=40 participants at risk
15-60 U/kg, every other week via intravenous infusion
|
|---|---|
|
Immune system disorders
Anaphylactoid reaction
|
2.5%
1/40 • Number of events 1 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Immune system disorders
Drug hypersensitivity
|
2.5%
1/40 • Number of events 1 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
2.5%
1/40 • Number of events 1 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
2.5%
1/40 • Number of events 1 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.5%
1/40 • Number of events 1 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
Other adverse events
| Measure |
GA-GCB (Velaglucerase Alfa)
n=40 participants at risk
15-60 U/kg, every other week via intravenous infusion
|
|---|---|
|
Vascular disorders
Hypertension
|
7.5%
3/40 • Number of events 15 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
General disorders
Fatigue
|
12.5%
5/40 • Number of events 13 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
General disorders
Influenza like illness
|
10.0%
4/40 • Number of events 5 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
General disorders
Malaise
|
5.0%
2/40 • Number of events 33 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
General disorders
Non-Cardiac chest pain
|
5.0%
2/40 • Number of events 3 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
General disorders
Pyrexia
|
12.5%
5/40 • Number of events 7 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Psychiatric disorders
Anxiety
|
5.0%
2/40 • Number of events 2 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Injury, poisoning and procedural complications
Fall
|
5.0%
2/40 • Number of events 2 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
5.0%
2/40 • Number of events 2 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Investigations
Activated partial thromboplastin time prolonged
|
5.0%
2/40 • Number of events 2 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Investigations
Blood glucose increased
|
7.5%
3/40 • Number of events 3 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.0%
6/40 • Number of events 6 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.5%
3/40 • Number of events 7 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.5%
3/40 • Number of events 6 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
15.0%
6/40 • Number of events 8 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
5.0%
2/40 • Number of events 2 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Nervous system disorders
Dizziness
|
7.5%
3/40 • Number of events 3 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Nervous system disorders
Headache
|
30.0%
12/40 • Number of events 29 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Nervous system disorders
Paraesthesia
|
7.5%
3/40 • Number of events 3 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Eye disorders
Conjunctivitis
|
5.0%
2/40 • Number of events 2 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Ear and labyrinth disorders
Ear pain
|
7.5%
3/40 • Number of events 3 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
12.5%
5/40 • Number of events 11 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Gastrointestinal disorders
Constipation
|
5.0%
2/40 • Number of events 2 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Gastrointestinal disorders
Diarrhoea
|
10.0%
4/40 • Number of events 4 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Gastrointestinal disorders
Nausea
|
10.0%
4/40 • Number of events 4 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Gastrointestinal disorders
Toothache
|
5.0%
2/40 • Number of events 3 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Gastrointestinal disorders
Vomiting
|
5.0%
2/40 • Number of events 2 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Renal and urinary disorders
Proteinuria
|
5.0%
2/40 • Number of events 2 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.0%
8/40 • Number of events 14 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
17.5%
7/40 • Number of events 10 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.0%
2/40 • Number of events 2 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
15.0%
6/40 • Number of events 7 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.5%
5/40 • Number of events 6 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
5.0%
2/40 • Number of events 3 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Infections and infestations
Bronchitis
|
7.5%
3/40 • Number of events 4 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Infections and infestations
Influenza
|
10.0%
4/40 • Number of events 4 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Infections and infestations
Nasopharyngitis
|
20.0%
8/40 • Number of events 10 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Infections and infestations
Pharyngitis
|
5.0%
2/40 • Number of events 2 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Infections and infestations
Rhinovirus infection
|
5.0%
2/40 • Number of events 2 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Infections and infestations
Upper respiratory tract infection
|
12.5%
5/40 • Number of events 7 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
|
Infections and infestations
Urinary tract infection
|
7.5%
3/40 • Number of events 3 • Time of informed consent until 30 days after the last dose and/or until the event was resolved/stabilized or outcome was reached, whichever came first. Participants who discontinued/withdrew prior to Week 53, and followed up to 30 days after last dose.
|
Additional Information
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