Trial Outcomes & Findings for Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) ERT Compared With Imiglucerase in Type I Gaucher Disease (NCT NCT00553631)

NCT ID: NCT00553631

Last Updated: 2021-06-08

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

34 participants

Primary outcome timeframe

Baseline to Month 9

Results posted on

2021-06-08

Participant Flow

The study was conducted in multiple sites from 29 January 2008 (first participant first enrolled) to 05 May 2009 (last participant completed).

Participants at least 2 years of age with type 1 Gaucher disease.Gaucher-disease-related anemia and at least 1 of the following: moderate splenomegaly, Gaucher-disease-related thrombocytopenia, readily palpable enlarged liver. Participants had not received treatment for Gaucher disease within 12 months prior to study entry.

Participant milestones

Participant milestones
Measure	Gene-Activated Human Glucocerebrosidase (GA-GCB) Velaglucerase alfa 60 unit per kilogram (U/kg) administered intravenously (IV) every other week for 39 weeks.	Imiglucerase Imiglucerase 60 U/kg administered IV every other week for 39 weeks.
Overall Study STARTED	17	17
Overall Study COMPLETED	16	16
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Gene-Activated Human Glucocerebrosidase (GA-GCB) Velaglucerase alfa 60 unit per kilogram (U/kg) administered intravenously (IV) every other week for 39 weeks.	Imiglucerase Imiglucerase 60 U/kg administered IV every other week for 39 weeks.
Overall Study Withdrawal by Subject	0	1
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) ERT Compared With Imiglucerase in Type I Gaucher Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gene-Activated Human Glucocerebrosidase (GA-GCB) n=17 Participants Velaglucerase alfa 60 U/kg administered IV every other week for 39 weeks.	Imiglucerase n=17 Participants Imiglucerase 60 U/kg administered IV every other week for 39 weeks.	Total n=34 Participants Total of all reporting groups
Age, Categorical <=18 years	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	36 years n=5 Participants	27 years n=7 Participants	30.5 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment United States	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Paraguay	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Argentina	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Spain	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Israel	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Russian Federation	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Tunisia	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United Kingdom	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment India	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Month 9

Population: Intent-to-treat (ITT) population comprised of all randomized participants who received at least 1 full or partial dose of study drug.

Outcome measures

Outcome measures
Measure	Gene-Activated Human Glucocerebrosidase (GA-GCB) n=17 Participants Velaglucerase alfa 60 U/kg administered IV every other week for 39 weeks.	Imiglucerase n=17 Participants Imiglucerase 60 U/kg administered IV every other week for 39 weeks.
Mean Change From Baseline to Month 9 in Hemoglobin (Hgb) Concentration for Each Treatment Group.	1.624 gram per deciliter (g/dl) Standard Error 0.223	1.488 gram per deciliter (g/dl) Standard Error 0.281

SECONDARY outcome

Timeframe: Baseline to Month 9

Population: ITT population.

Values shown are observed change from Baseline to Month 9.

Outcome measures

Outcome measures
Measure	Gene-Activated Human Glucocerebrosidase (GA-GCB) n=17 Participants Velaglucerase alfa 60 U/kg administered IV every other week for 39 weeks.	Imiglucerase n=17 Participants Imiglucerase 60 U/kg administered IV every other week for 39 weeks.
Change From Baseline to Month 9 in Platelet Counts for Each Treatment Group.	110.41 10^9 per liter (10^9/L) Standard Error 17.159	144.38 10^9 per liter (10^9/L) Standard Error 22.76

SECONDARY outcome

Timeframe: Baseline to Month 9

Population: ITT population.

Values shown are observed change from Baseline to Month 9. Measured by Magnetic resonance imaging (MRI). Liver volume has been normalized for percent (%) body weight for each treatment arm. Liver size relative to body weight = (Liver volume \[cubic centimeter (cc)\]/Body weight \[kg\]\*1000.

Outcome measures

Outcome measures
Measure	Gene-Activated Human Glucocerebrosidase (GA-GCB) n=17 Participants Velaglucerase alfa 60 U/kg administered IV every other week for 39 weeks.	Imiglucerase n=17 Participants Imiglucerase 60 U/kg administered IV every other week for 39 weeks.
Change From Baseline to Month 9 in Normalized Liver Volume (Percent (%) Body Weight) for Each Treatment Group.	-1.31 cubic centimeter (cm^3) Standard Error 0.347	-1.10 cubic centimeter (cm^3) Standard Error 0.182

SECONDARY outcome

Timeframe: Baseline to Month 9

Population: ITT population. Number of participants analyzed signifies participants evaluable for this outcome. Ten participants in each treatment group underwent splenectomy, and therefore, were excluded from the analysis.

Values shown are observed change from Baseline to month 9. Measured by Magnetic resonance imaging (MRI). Spleen volume was 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

Outcome measures
Measure	Gene-Activated Human Glucocerebrosidase (GA-GCB) n=7 Participants Velaglucerase alfa 60 U/kg administered IV every other week for 39 weeks.	Imiglucerase n=7 Participants Imiglucerase 60 U/kg administered IV every other week for 39 weeks.
Change From Baseline to Month 9 in Normalized Spleen Volume (Percent (%) Body Weight) for Each Treatment Group.	-1.34 cm^3 Standard Error 0.424	-2.46 cm^3 Standard Error 0.966

SECONDARY outcome

Timeframe: Baseline to Month 9.

Population: ITT population. Number of participants analyzed signifies participants evaluable for this outcome. Chitotriosidase levels were measured in 10 participants in the velaglucerase alfa group and 11 participants in the imiglucerase group.

Values shown are observed change from Baseline to Month 9. Units of measure is defined as nanomole per milliliter per hour.

Outcome measures

Outcome measures
Measure	Gene-Activated Human Glucocerebrosidase (GA-GCB) n=10 Participants Velaglucerase alfa 60 U/kg administered IV every other week for 39 weeks.	Imiglucerase n=11 Participants Imiglucerase 60 U/kg administered IV every other week for 39 weeks.
Change From Baseline to Month 9 in Plasma Chitotriosidase for Each Treatment Group.	-34711.9 nanomole/milliliter/hour (nmol/mL/h) Standard Error 6887.77	-35109.5 nanomole/milliliter/hour (nmol/mL/h) Standard Error 7310.22

SECONDARY outcome

Timeframe: Baseline to Month 9

Population: ITT population.

Values shown are observed change from Baseline to Month 9.

Outcome measures

Outcome measures
Measure	Gene-Activated Human Glucocerebrosidase (GA-GCB) n=17 Participants Velaglucerase alfa 60 U/kg administered IV every other week for 39 weeks.	Imiglucerase n=17 Participants Imiglucerase 60 U/kg administered IV every other week for 39 weeks.
Change From Baseline to Month 9 in Plasma Chemokine (C-C Motif) Ligand 18 (CCL18) for Each Treatment Group.	-926.2 nanogram per milliliter (ng/mL) Standard Error 113.29	-1153.4 nanogram per milliliter (ng/mL) Standard Error 269.63

SECONDARY outcome

Timeframe: Baseline to Month 9

Population: Safety population comprised of all randomized participants who received at least 1 full or partial dose of study drug.

Measure type is actual number of participants who developed antibodies to treatment; GA-GCB or imiglucerase. Antibody detection was based upon serum samples collected at various time points throughout the study. Serum samples were screened using an enzyme-linked immunosorbent assay (ELISA) and positive antibody confirmation was determined using a radioimmunoprecipitation assay (RIP); positive samples were also tested for enzyme neutralizing activity. Participant samples were compared to internal assay controls (positive/negative), positive samples were determined based upon individual assay criteria.

Outcome measures

Outcome measures
Measure	Gene-Activated Human Glucocerebrosidase (GA-GCB) n=17 Participants Velaglucerase alfa 60 U/kg administered IV every other week for 39 weeks.	Imiglucerase n=17 Participants Imiglucerase 60 U/kg administered IV every other week for 39 weeks.
Number of Participants Who Developed Antibody for Each Treatment Group.	0 participants	4 participants

SECONDARY outcome

Timeframe: Response rate at Month 9 compared to Baseline

Population: ITT population

Time to response was defined as a ≥ 1 g/dL improvement in hemoglobin levels relative to Baseline. Units (%) correlates to the percentage of participants who had a change of ≥ 1 g/dL improvement in hemoglobin levels relative to Baseline during their participation in the study.

Outcome measures

Outcome measures
Measure	Gene-Activated Human Glucocerebrosidase (GA-GCB) n=17 Participants Velaglucerase alfa 60 U/kg administered IV every other week for 39 weeks.	Imiglucerase n=17 Participants Imiglucerase 60 U/kg administered IV every other week for 39 weeks.
Time to Response- Comparison of GA-GCB and Imiglucerase on the Earliest Time to Respond as Assessed Via Hemoglobin Concentration	92.9 Percentage of participants	100 Percentage of participants

Adverse Events

Gene-Activated Human Glucocerebrosidase (GA-GCB)

Serious events: 3 serious events

Other events: 16 other events

Deaths: 0 deaths

Imiglucerase

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Gene-Activated Human Glucocerebrosidase (GA-GCB) n=17 participants at risk Velaglucerase alfa 60 U/kg administered IV every other week for 39 weeks.	Imiglucerase n=17 participants at risk Imiglucerase 60 U/kg administered IV every other week for 39 weeks.
Skin and subcutaneous tissue disorders Dermatitis allergic	5.9% 1/17 • Number of events 1 • Adverse events (AE) monitored from time informed consent/assent obtained through 30 days after the last infusion. For participants who completed this study and elected to enroll in the long-term extension study, AEs were monitored through the Week 41. AE may have been discovered via observation, examination, questioning or complaint by participants.Unexpected laboratory values that became significantly out of range and determined to be clinically significant by the investigator could have been reported as AEs.Other AE were determined to be possibly/probably related to GA-GCB by the investigator.	0.00% 0/17 • Adverse events (AE) monitored from time informed consent/assent obtained through 30 days after the last infusion. For participants who completed this study and elected to enroll in the long-term extension study, AEs were monitored through the Week 41. AE may have been discovered via observation, examination, questioning or complaint by participants.Unexpected laboratory values that became significantly out of range and determined to be clinically significant by the investigator could have been reported as AEs.Other AE were determined to be possibly/probably related to GA-GCB by the investigator.
Blood and lymphatic system disorders Thrombocytopenia	5.9% 1/17 • Number of events 2 • Adverse events (AE) monitored from time informed consent/assent obtained through 30 days after the last infusion. For participants who completed this study and elected to enroll in the long-term extension study, AEs were monitored through the Week 41. AE may have been discovered via observation, examination, questioning or complaint by participants.Unexpected laboratory values that became significantly out of range and determined to be clinically significant by the investigator could have been reported as AEs.Other AE were determined to be possibly/probably related to GA-GCB by the investigator.	0.00% 0/17 • Adverse events (AE) monitored from time informed consent/assent obtained through 30 days after the last infusion. For participants who completed this study and elected to enroll in the long-term extension study, AEs were monitored through the Week 41. AE may have been discovered via observation, examination, questioning or complaint by participants.Unexpected laboratory values that became significantly out of range and determined to be clinically significant by the investigator could have been reported as AEs.Other AE were determined to be possibly/probably related to GA-GCB by the investigator.
Nervous system disorders Convulsions	5.9% 1/17 • Number of events 1 • Adverse events (AE) monitored from time informed consent/assent obtained through 30 days after the last infusion. For participants who completed this study and elected to enroll in the long-term extension study, AEs were monitored through the Week 41. AE may have been discovered via observation, examination, questioning or complaint by participants.Unexpected laboratory values that became significantly out of range and determined to be clinically significant by the investigator could have been reported as AEs.Other AE were determined to be possibly/probably related to GA-GCB by the investigator.	0.00% 0/17 • Adverse events (AE) monitored from time informed consent/assent obtained through 30 days after the last infusion. For participants who completed this study and elected to enroll in the long-term extension study, AEs were monitored through the Week 41. AE may have been discovered via observation, examination, questioning or complaint by participants.Unexpected laboratory values that became significantly out of range and determined to be clinically significant by the investigator could have been reported as AEs.Other AE were determined to be possibly/probably related to GA-GCB by the investigator.

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

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