Trial Outcomes & Findings for High Dose or High Dose Frequency Study of Alglucosidase Alfa (NCT NCT00483379)

Last Updated: 2014-03-07

Results Overview

Participants were enrolled based on clinical decline or sub-optimal clinical response in cardiac, respiratory and/or motor function parameters pre-study while on standard treatment. Each participant was evaluated at Week 52 for change from baseline in the criteria that declined; respiratory decline as measured by change in ventilator use is summarized in this outcome. Ventilator use might have improved (less use of ventilator support), had no change, or worsened (more use of ventilator support). Each participant served as his or her own control.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

13 participants

Primary outcome timeframe

Baseline, Week 52

Results posted on

2014-03-07

Participant Flow

Fourteen participants were screened and enrolled; however, one withdrew before receiving any study infusions due to the burden of weekly trips to the medical center.

Participant milestones

Participant milestones
Measure	Alglucosidase Alfa 20 mg/kg Every Week Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Treatment Period STARTED	6	7
Treatment Period COMPLETED	4	7
Treatment Period NOT COMPLETED	2	0
Extension Period STARTED	1	2
Extension Period COMPLETED	1	2
Extension Period NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Alglucosidase Alfa 20 mg/kg Every Week Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Treatment Period Adverse Event	1	0
Treatment Period Withdrawal by Subject	1	0

Baseline Characteristics

High Dose or High Dose Frequency Study of Alglucosidase Alfa

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=6 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=7 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.	Total n=13 Participants Total of all reporting groups
Age, Continuous	23.3 years STANDARD_DEVIATION 27.75 • n=5 Participants	16.8 years STANDARD_DEVIATION 15.56 • n=7 Participants	19.8 years STANDARD_DEVIATION 21.29 • n=5 Participants
Age, Customized <18 years	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Age, Customized >= 18 and <=65 years	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Age, Customized >65 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Life-stage of Disease Onset Infantile-onset Pompe Disease	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Life-stage of Disease Onset Late-onset Pompe Disease	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Parameter in Clinical Decline Cardiac	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Parameter in Clinical Decline Respiratory	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Parameter in Clinical Decline Motor Skills	5 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants
Cross-Reactive Immunologic Material (CRIM) Assay Result Positive	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Cross-Reactive Immunologic Material (CRIM) Assay Result Negative	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Cross-Reactive Immunologic Material (CRIM) Assay Result Unknown	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52

Population: All participants who enrolled due to decline in respiratory function while on standard treatment.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=1 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=1 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment Improved	0 participants	0 participants
Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment No change (on invasive ventilator for 24 hrs)	0 participants	1 participants
Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment Worsened	0 participants	0 participants
Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment Not evaluated	1 participants	0 participants

PRIMARY outcome

Timeframe: Baseline, Week 52

Population: All participants who enrolled due to decline in motor function while on standard treatment.

Participants were enrolled based on clinical decline or sub-optimal clinical response in cardiac, respiratory and/or motor function parameters pre-study while on standard treatment. Each participant was evaluated at Week 52 for change from baseline in the criteria that declined; motor function decline primarily based on Gross Motor Function Measure 66 and Pompe Pediatric Evaluation of Disability Inventory results is summarized. Participants could gain motor function (improve), had no change (declined stopped), or continued loss (worsened). Each participant served as his or her own control.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=5 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=6 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment Gained gross or fine motor skills	2 participants	4 participants
Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment No change	1 participants	2 participants
Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment Continued motor loss	1 participants	0 participants
Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment Not evaluated	1 participants	0 participants

PRIMARY outcome

Timeframe: Day 1 up to Week 52

Population: Safety population comprised of all participants who received intervention.

Overall safety summary of participants experiencing Adverse Events (AEs), Serious Adverse Events (SAEs), treatment-related AEs, and Infusion Associated Reactions (IARs). Summary is based on Treatment-emergent AEs (TEAEs), defined as AEs that occurred following the initiation of study treatment.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=6 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=7 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period Participants with AEs	6 participants	7 participants
Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period Related AEs	0 participants	2 participants
Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period Not related AEs	6 participants	7 participants
Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period Mild AEs	6 participants	6 participants
Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period Moderate AEs	3 participants	2 participants
Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period Severe AEs	2 participants	0 participants
Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period AEs leading to discontinuation from study	1 participants	0 participants
Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period Deaths	1 participants	0 participants
Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period Infusion Associated Reactions	0 participants	2 participants
Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period Serious AEs	2 participants	1 participants

SECONDARY outcome

Timeframe: Day 0

Population: Full analysis population of participants with LVM data

Z-Scores indicate the number of standard deviations (SD) from the mean in a normal distribution. Negative values indicate a smaller than mean LVM and values higher than 0 indicate a larger LVM than the mean. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy. The Z-scores for all parameters are calculated with reference to the normative data from the Children's Hospital, Boston, MA (Colan, 1992, J Am Coll Cardiol) based on the reference population with matched body surface area (BSA). Z-scores for LVM were provided by the central cardiologist.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=5 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=5 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Baseline Values for Left Ventricular Mass (LVM) Z-Scores	0.3 Z-score Interval -1.2 to 6.3	-0.3 Z-score Interval -1.2 to 2.2

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Full analysis population of participants with LVM data at both timepoints

Z-Scores indicate the number of standard deviations (SD) from the mean in a normal distribution. A negative change from baseline indicates a decrease and positive change from baseline an increase in LVM Z-score. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy. The Z-scores for all parameters are calculated with reference to the normative data from the Children's Hospital, Boston, MA (Colan, 1992, J Am Coll Cardiol) based on the reference population with matched body surface area (BSA). Z-scores for LVM were provided by the central cardiologist.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=3 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=3 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Change From Baseline in Left Ventricular Mass (LVM) Z-Score at Week 52	0.3 Z-score Full Range 1.04 • Interval -0.8 to 1.2	0.4 Z-score Full Range 0.33 • Interval -0.1 to 0.5

SECONDARY outcome

Timeframe: Day 0

Population: Full analysis population of participants with LVMI data

Cardiac pathophysiology was assessed by a central cardiologist using left ventricular mass index (LVMI) measured by echocardiogram at Baseline. Left Ventricular Mass is adjusted to the participant's body surface area in the calculation of LVMI.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=5 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=5 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Baseline Values for Left Ventricular Mass Index (LVMI)	62.1 g/m^2 Interval 49.0 to 187.3	56.5 g/m^2 Interval 45.4 to 73.1

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Full analysis population of participants with LVMI data at both timepoints

Cardiac pathophysiology was assessed by a central cardiologist using left ventricular mass index (LVMI) measured by echocardiogram at Baseline and after 12 months of treatment (Week 52). Left Ventricular Mass is adjusted to the participant's body surface area in the calculation of LVMI.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=3 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=3 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Change From Baseline in Left Ventricular Mass Index (LVMI) at Week 52	12.5 g/m^2 Full Range 14.44 • Interval -10.9 to 15.5	4.0 g/m^2 Full Range 5.95 • Interval -5.3 to 5.8

SECONDARY outcome

Timeframe: Baseline, approximately Week 52

Population: Full analysis population. The participant in the worsened category died after week 52.

The change from baseline in ventilator use at the last assessment is summarized as improved (less use of ventilator support), no change, worsened (increased use of ventilator support), and did not use ventilator support.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=6 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=7 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52) Improved	0 participants	0 participants
Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52) No change	2 participants	3 participants
Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52) Worsened	1 participants	0 participants
Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52) Did not use ventilator	3 participants	4 participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Full analysis population of participants \>= 8 years old. Due to the age restriction and small study population, the number of participants analyzed is too small for results to be meaningful.

Body strength is measured by the MMT score on a scale of 0-10 with higher scores representing greater body strength.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 0

Population: Full analysis population

The Gross Motor Function Measure 66 contains sixty-six questions with a total raw score range of 0 - 198. Raw scores are derived from the following dimensions: Lying and rolling = 12; Sitting = 45; Crawling and kneeling = 30; Standing = 39; Walking, running and jumping = 72. Higher scores indicate better gross motor functions.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=6 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=6 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Baseline Values of Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results	65.0 units on a scale Standard Deviation 60.52	82.8 units on a scale Standard Deviation 84.00

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Full analysis population

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=4 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=6 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Change From Baseline in Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results at Week 52	6.0 units on a scale Standard Deviation 8.49	6.7 units on a scale Standard Deviation 6.12

SECONDARY outcome

Timeframe: Day 0

Population: Full analysis population

The Pompe PEDI is a disease specific version of the PEDI that was developed to assess functional capabilities and performance in children with Pompe disease from 2 months through adolescence. Baseline results for the mobility domain are reported. Scaled scores are used as an evaluative measure of change in performance over time with acquisition of new skills or new levels of independence. The range of scores is from 0-100 with scores near "0" reflecting low capability and scores near "100" reflecting high capability.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=6 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=7 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Baseline Values in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI)	38.3 units on a scale Standard Deviation 20.94	46.8 units on a scale Standard Deviation 21.26

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Full analysis population

The Pompe PEDI is a disease specific version of the PEDI that was developed to assess functional capabilities and performance in children with Pompe disease from 2 months through adolescence. Change from baseline results for the mobility domain are reported. Scaled scores are used as an evaluative measure of change in performance over time with acquisition of new skills or new levels of independence. The range of scores is from 0-100 with scores near "0" reflecting low capability and scores near "100" reflecting high capability.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=4 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=7 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Change From Baseline in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) at Week 52	0.6 units on a scale Standard Deviation 4.28	3.5 units on a scale Standard Deviation 3.84

SECONDARY outcome

Timeframe: Day 0

Population: Full analysis population of participants \>= 14 years old.

Health related quality of life is measured using the Physical Component Summary (PCS) score of the Medical Outcomes Study (MOS) Short Form Health Survey (SF-36) for participants ≥14 years of age. SF-36 normative-based scoring has a mean of 50 and a standard deviation of 10. Higher scores represent better quality of life.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=2 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=3 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Baseline Values for Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36)	31.3 units on a scale Standard Deviation 2.84	36.0 units on a scale Standard Deviation 9.33

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Full analysis population of participants \>= 14 years old.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 20 mg/kg Every Week n=1 Participants Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Alglucosidase Alfa 40 mg/kg Every Other Week n=3 Participants Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.
Change From Baseline in Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36) at Week 52	2.5 units on a scale	4.4 units on a scale Standard Deviation 11.24

Adverse Events

Treatment: Alglucosidase Alfa 20 mg/kg Every Week

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Treatment: Alglucosidase Alfa 40 mg/kg Every Other Week

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Extension: Alglucosidase Alfa 20 mg/kg Every Week

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Extension: Alglucosidase Alfa 40 mg/kg Every Other Week

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment: Alglucosidase Alfa 20 mg/kg Every Week n=6 participants at risk Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.	Treatment: Alglucosidase Alfa 40 mg/kg Every Other Week n=7 participants at risk Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.	Extension: Alglucosidase Alfa 20 mg/kg Every Week n=1 participants at risk The extension period of the study allowed late-onset participants access to the same treatment they took in the treatment period until the product was commercially available.	Extension: Alglucosidase Alfa 40 mg/kg Every Other Week n=2 participants at risk The extension period of the study allowed late-onset participants access to the same treatment they took in the treatment period until the product was commercially available.
Cardiac disorders Supraventricular tachycardia	0.00% 0/6 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	14.3% 1/7 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/1 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/2 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Dysphagia	0.00% 0/6 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	14.3% 1/7 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/1 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/2 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Device related infection	0.00% 0/6 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	14.3% 1/7 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/1 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/2 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Pneumonia	33.3% 2/6 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/7 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/1 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/2 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/6 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/7 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	100.0% 1/1 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/2 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Weight decreased	0.00% 0/6 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	14.3% 1/7 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/1 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/2 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Respiratory failure	16.7% 1/6 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/7 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/1 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.	0.00% 0/2 • Treatment period AEs were collected up to week 52. Extension period AEs were collected following completion of the treatment period until the product was commercially available (up to week 118). In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.

Other adverse events

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