A Noninferiority Study of Alglucosidase Alfa Manufactured at the 160 L and 4000 L Scales in Treatment Naïve Patients With Infantile-Onset Pompe Disease

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01597596
• Collaborator: (none)
• Enrollment: 4
• Locations: 17
• Arms: 2
• Duration (Months): 28
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

A study to demonstrate comparable safety, efficacy, and pharmacokinetics (PK) of alglucosidase alfa manufactured at the 160 litre (L) and 4000 L scales in participants who had been diagnosed with infantile-onset Pompe disease. Participants were treated with alglucosidase alfa 160 L scale product in the United States (US) and 4000 L scale product in the regions outside the US.

Condition or Disease	Intervention/Treatment	Phase
Pompe Disease (Infantile-Onset); Glycogen Storage Disease Type II (GSD II); Glycogenosis 2; Acid Maltase Deficiency	Biological: alglucosidase alfa; Biological: alglucosidase alfa	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3/4, Prospective, Multinational, Open-label, Noninferiority Study of Alglucosidase Alfa Manufactured at the 160 L and 4000 L Scales in Treatment Naïve Patients With Infantile-Onset Pompe Disease
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alglucosidase Alfa 4000 L material (Non-US participants) Alglucosidase alfa 4000 L material for 52 weeks.	Biological: alglucosidase alfa; Intravenous (IV) infusion of alglucosidase alfa (4000 L material) 20 mg/kg every other week (QOW); Other Names: Lumizyme
Active Comparator: Alglucosidase Alfa 160 L material (US participants) Alglucosidase alfa 160 L material for 52 weeks.	Biological: alglucosidase alfa; IV infusion of alglucosidase alfa (160 L material) 20 mg/kg QOW.; Other Names: Myozyme

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Cardiac Function at Week 52 [Baseline, Week 52]

   Cardiac function was measured by the left ventricular mass Z-score (LVM-Z). 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 indicates an increase in LVM Z-score. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy.

Secondary Outcome Measures

1. Percentage of Participants With Estimated Probability of Survival [Up to Week 52]

2. Number of Participants With Invasive Ventilator-Free Survival [Up to Week 52]

   Invasive ventilator-free survival was defined as the time during which the participant is alive and not invasively ventilated. Number of Participants with invasive ventilator-free survival were reported.

3. Change From Baseline in Motor Development Status at Week 52 [Baseline, Week 52]

   Motor development status was assessed by the Gross Motor Function Measure - 88 Scale (GMFM-88) total percent scores. GMFM-88 is an 88-item measure to detect gross motor function. It consists of 5 categories: lying and rolling; sitting; crawling and kneeling; standing; walking, running and jumping. Each item was scored on a 4-point Likert scale (0 = cannot do; 1 = initiates [<10% of the task]; 2 = partially completes [10% to <100% of the task]; 3 = task completion). The score for each dimension was expressed as a percentage of the maximum score for that dimension. Total score ranges from 0% to 100%, where higher scores indicate better motor functions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 12 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The participant's parent/legal guardian was willing and able to provide signed informed consent.

• The participant might be less than or equal to 12 months of age.

• The participant might have documented GAA enzyme deficiency from blood, skin, or muscle tissue.

• The participant might be naïve to treatment with alglucosidase alfa.

Exclusion Criteria:

• The participant was cross-reactive immunologic material negative.

• The participant required invasive ventilator support at the time of enrollment.

• The participant had decompensated clinical heart failure.

• The participant had a major congenital abnormality, excluding cardiac hypertrophy.

• The participant had a clinically significant organ disease (excluding the signs and symptoms of Pompe disease).

• The participant was currently receiving any investigational product.

• The participant was participating in another clinical study.

• The participant and/or the patient's parent/legal guardian was unable to adhere to the requirements of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Little Rock	Arkansas	United States
2		Oakland	California	United States
3		Gainsville	Florida	United States
4		Decatur	Georgia	United States
5		Chicago	Illinois	United States
6		Cambridge	Massachusetts	United States
7		Detroit	Michigan	United States
8		Las Vegas	Nevada	United States
9		New Brunswick	New Jersey	United States
10		New York	New York	United States
11		Durham	North Carolina	United States
12		Cincinnati	Ohio	United States
13		Fort Worth	Texas	United States
14		Seattle	Washington	United States
15		Geiben		Germany
16		Mainz		Germany
17		Taipei		Taiwan

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Medical Monitor, Genzyme, a Sanofi Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01597596
• Other Study ID Numbers: AGLU07510; 2011-005595-42
• First Posted: May 14, 2012
• Last Update Posted: Jan 18, 2016
• Last Verified: Dec 1, 2015

• Additional relevant MeSH terms: Glycogen Storage Disease Type II; Glycogen Storage Disease

Study Results

Participant Flow

Recruitment Details	The study was conducted between 21 August 2012 and 1 December 2014.
Pre-assignment Detail	A total of 5 participants were screened and 4 participants were treated.

Arm/Group Title	Alglucosidase Alfa 4000 L Material (Non-US Participants)	Alglucosidase Alfa 160 L Material (US Participants)
Arm/Group Description	Alglucosidase alfa (4000 L material) 20 mg/kg intravenous (IV) infusion every other week (QOW) for 52 weeks.	Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.
Period Title: Overall Study
STARTED	1	3
COMPLETED	0	2
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Alglucosidase Alfa 4000 L Material (Non-US Participants)	Alglucosidase Alfa 160 L Material (US Participants)	Total
Arm/Group Description	Alglucosidase alfa (4000 L material) 20 mg/kg IV infusion QOW for 52 weeks.	Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.	Total of all reporting groups
Overall Participants	1	3	4
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	0.3	0.5 (0.28)	0.4 (0.14)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	3 100%	4 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Cardiac Function at Week 52
Description	Cardiac function was measured by the left ventricular mass Z-score (LVM-Z). 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 indicates an increase in LVM Z-score. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Full analysis population defined as all participants who receive at least 1 infusion of alglucosidase alfa. For this endpoint no participants were analyzed in 'Algucosidase Alfa 4000 L material' arm at Baseline and Week 52. One participant from 'Algucosidase Alfa 160 L Material' arm was discontinued from study at Week 31 due to physician's decision

Arm/Group Title	Alglucosidase Alfa 4000 L Material (Non-US Participants)	Alglucosidase Alfa 160 L Material (US Participants)
Arm/Group Description	Alglucosidase alfa (4000 L material) 20 mg/kg IV infusion QOW for 52 weeks.	Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.
Measure Participants	0	2
Mean (Standard Deviation) [Z-score]	-5.06 (1.103)

2. Secondary Outcome

Title	Percentage of Participants With Estimated Probability of Survival
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Full analysis population.

Arm/Group Title	Alglucosidase Alfa 4000 L Material (Non-US Participants)	Alglucosidase Alfa 160 L Material (US Participants)
Arm/Group Description	Alglucosidase alfa (4000 L material) 20 mg/kg IV infusion QOW for 52 weeks.	Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.
Measure Participants	1	3
Number [percentage of participants]	100 10000%	100 3333.3%

3. Secondary Outcome

Title	Number of Participants With Invasive Ventilator-Free Survival
Description	Invasive ventilator-free survival was defined as the time during which the participant is alive and not invasively ventilated. Number of Participants with invasive ventilator-free survival were reported.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Full analysis population.

Arm/Group Title	Alglucosidase Alfa 4000 L Material (Non-US Participants)	Alglucosidase Alfa 160 L Material (US Participants)
Arm/Group Description	Alglucosidase alfa (4000 L material) 20 mg/kg IV infusion QOW for 52 weeks.	Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.
Measure Participants	1	3
Number [participants]	1 100%	2 66.7%

4. Secondary Outcome

Title	Change From Baseline in Motor Development Status at Week 52
Description	Motor development status was assessed by the Gross Motor Function Measure - 88 Scale (GMFM-88) total percent scores. GMFM-88 is an 88-item measure to detect gross motor function. It consists of 5 categories: lying and rolling; sitting; crawling and kneeling; standing; walking, running and jumping. Each item was scored on a 4-point Likert scale (0 = cannot do; 1 = initiates [<10% of the task]; 2 = partially completes [10% to <100% of the task]; 3 = task completion). The score for each dimension was expressed as a percentage of the maximum score for that dimension. Total score ranges from 0% to 100%, where higher scores indicate better motor functions.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Full analysis population. For this endpoint no participants were analyzed in 'Algucosidase Alfa 4000 L material' arm at Baseline and Week 52. One participant from 'Algucosidase Alfa 160 L Material' arm was discontinued from study at Week 31 due to physician's decision.

Arm/Group Title	Alglucosidase Alfa 4000 L Material (Non-US Participants)	Alglucosidase Alfa 160 L Material (US Participants)
Arm/Group Description	Alglucosidase alfa (4000 L material) 20 mg/kg IV infusion QOW for 52 weeks.	Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.
Measure Participants	0	2
Mean (Standard Deviation) [percentage of maximum total score]	48.65 (17.183)

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.
Arm/Group Title	Alglucosidase Alfa 4000 L Material (Non-US Participants)		Alglucosidase Alfa 160 L Material (US Participants)
Arm/Group Description	Alglucosidase alfa (4000 L material) 20 mg/kg IV infusion QOW for 52 weeks.		Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.
All Cause Mortality
	Alglucosidase Alfa 4000 L Material (Non-US Participants)		Alglucosidase Alfa 160 L Material (US Participants)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Alglucosidase Alfa 4000 L Material (Non-US Participants)		Alglucosidase Alfa 160 L Material (US Participants)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		3/3 (100%)
Cardiac disorders
Cardiac failure	0/1 (0%)		1/3 (33.3%)
General disorders
Pyrexia	0/1 (0%)		1/3 (33.3%)
Infections and infestations
Adenovirus infection	0/1 (0%)		1/3 (33.3%)
Lobar pneumonia	0/1 (0%)		1/3 (33.3%)
Otitis media acute	0/1 (0%)		1/3 (33.3%)
Respiratory syncytial virus infection	0/1 (0%)		1/3 (33.3%)
Upper respiratory tract infection	0/1 (0%)		1/3 (33.3%)
Nervous system disorders
Hypotonia	0/1 (0%)		1/3 (33.3%)
Syncope	0/1 (0%)		1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema	0/1 (0%)		1/3 (33.3%)
Respiratory failure	0/1 (0%)		1/3 (33.3%)
Skin and subcutaneous tissue disorders
Urticaria	0/1 (0%)		1/3 (33.3%)
Other (Not Including Serious) Adverse Events
	Alglucosidase Alfa 4000 L Material (Non-US Participants)		Alglucosidase Alfa 160 L Material (US Participants)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anaemia	0/1 (0%)		1/3 (33.3%)
Cardiac disorders
Cardiac failure	0/1 (0%)		2/3 (66.7%)
Cardiac failure congestive	0/1 (0%)		1/3 (33.3%)
Cardiomyopathy	0/1 (0%)		1/3 (33.3%)
Nodal rhythm	0/1 (0%)		1/3 (33.3%)
Ear and labyrinth disorders
Middle ear effusion	0/1 (0%)		1/3 (33.3%)
Gastrointestinal disorders
Abdominal pain	1/1 (100%)		0/3 (0%)
Diarrhoea	0/1 (0%)		1/3 (33.3%)
Vomiting	0/1 (0%)		1/3 (33.3%)
General disorders
Device occlusion	0/1 (0%)		1/3 (33.3%)
Infusion site erythema	0/1 (0%)		1/3 (33.3%)
Pyrexia	1/1 (100%)		3/3 (100%)
Infections and infestations
Bronchitis	0/1 (0%)		1/3 (33.3%)
Croup infectious	0/1 (0%)		1/3 (33.3%)
Eye infection	0/1 (0%)		1/3 (33.3%)
Fungal infection	0/1 (0%)		1/3 (33.3%)
Nasopharyngitis	0/1 (0%)		1/3 (33.3%)
Pneumonia	0/1 (0%)		1/3 (33.3%)
Urinary tract infection	0/1 (0%)		1/3 (33.3%)
Injury, poisoning and procedural complications
Arthropod bite	0/1 (0%)		1/3 (33.3%)
Investigations
Oxygen saturation decreased	0/1 (0%)		1/3 (33.3%)
Musculoskeletal and connective tissue disorders
Muscle contracture	0/1 (0%)		1/3 (33.3%)
Nervous system disorders
Nystagmus	0/1 (0%)		1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Aspiration	0/1 (0%)		1/3 (33.3%)
Asthma	0/1 (0%)		1/3 (33.3%)
Bronchial secretion retention	1/1 (100%)		0/3 (0%)
Cough	0/1 (0%)		1/3 (33.3%)
Hypoxia	0/1 (0%)		1/3 (33.3%)
Nasal congestion	0/1 (0%)		1/3 (33.3%)
Pleural effusion	0/1 (0%)		1/3 (33.3%)
Respiratory disorder	0/1 (0%)		1/3 (33.3%)
Rhinorrhoea	0/1 (0%)		1/3 (33.3%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/1 (0%)		1/3 (33.3%)
Dermatitis diaper	0/1 (0%)		1/3 (33.3%)
Rash erythematous	0/1 (0%)		1/3 (33.3%)
Rash pruritic	0/1 (0%)		1/3 (33.3%)
Urticaria	0/1 (0%)		1/3 (33.3%)
Vascular disorders
Hypotension	0/1 (0%)		1/3 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.