A Placebo-Controlled Study of Safety and Effectiveness of Myozyme (Alglucosidase Alfa) in Patients With Late-Onset Pompe Disease

This study has been completed.
Sponsor:
Information provided by:
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00158600
First received: September 8, 2005
Last updated: June 24, 2010
Last verified: June 2010
Results First Received: June 24, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Pompe Disease (Late-onset)
Glycogen Storage Disease Type II (GSD-II)
Acid Maltase Deficiency Disease
Glycogenosis 2
Interventions: Biological: alglucosidase alfa
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
One hundred patients screened and 90 enrolled.

Reporting Groups
  Description
Alglucosidase Alfa Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.
Placebo Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks.

Participant Flow:   Overall Study
    Alglucosidase Alfa     Placebo  
STARTED     60     30  
COMPLETED     55     26  
NOT COMPLETED     5     4  
unable to commit time to study                 0                 1  
Adverse Event                 2                 1  
Death                 1                 0  
Withdrawal by Subject                 2                 2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Alglucosidase Alfa Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.
Placebo Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks.
Total Total of all reporting groups

Baseline Measures
    Alglucosidase Alfa     Placebo     Total  
Number of Participants  
[units: participants]
  60     30     90  
Age [1]
[units: years]
Mean ± Standard Deviation
  45.3  ± 12.37     42.6  ± 11.63     44.4  ± 12.14  
Gender  
[units: participants]
     
Female     26     19     45  
Male     34     11     45  
Race/Ethnicity, Customized  
[units: participants]
     
Hispanic     1     1     2  
Asian     1     1     2  
Black or African American     0     0     0  
White     57     27     84  
Unknown or not reported     1     1     2  
[1] Age at First Infusion



  Outcome Measures
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1.  Primary:   Summary of Patients Reporting Treatment-Emergent Adverse Events   [ Time Frame: weeks 0-78 ]

2.  Primary:   Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline   [ Time Frame: weeks 0, 78 ]
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Measure Type Primary
Measure Title Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline
Measure Description Mean distance walked gives an indication of functional endurance. The greater the distance, the greater the endurance. Mean values of distance walked in a six-minute walk test are offered for baseline, week 78 (or last available observation), and the mean change from baseline (at week 78 or last available post-baseline observation).
Time Frame weeks 0, 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) population. Last observation carried forward. The last available distance walked for one patient was the Baseline visit; therefore, this patient was excluded from the change from baseline calculation.

Reporting Groups
  Description
Alglucosidase Alfa Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.
Placebo Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks.

Measured Values
    Alglucosidase Alfa     Placebo  
Number of Participants Analyzed  
[units: participants]
  60     30  
Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline  
[units: meters]
Mean ± Standard Deviation
   
Distance Walked at Baseline     332.20  ± 126.69     317.93  ± 132.29  
Distance Walked at Last Available Observation     357.85  ± 141.32     313.07  ± 144.69  
Change at Last Available Observation from Baseline     26.08  ± 64.41     -4.87  ± 45.24  


Statistical Analysis 1 for Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0347
Difference [4] 28.12
95% Confidence Interval ( 2.07 to 54.17 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The difference between alglucosidase alfa and placebo treatment groups in change in distance walked from baseline to last observation was estimated by ANCOVA after adjusting for baseline value and randomization strata.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The threshold for determining statistical significance is 0.05. A fixed testing sequence procedure was used to preserve an overall error rate of 5% for the co-primary efficacy endpoints by linking the test of FVC to the result of 6MWT.
[4] Other relevant estimation information:
  No text entered.



3.  Primary:   Percent of Predicted Forced Vital Capacity (FVC)   [ Time Frame: weeks 0, 78 ]

4.  Primary:   Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Area Under the Curve (AUC)   [ Time Frame: weeks 0, 12 and 52 ]

5.  Primary:   Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Maximum Plasma Concentration(Cmax)   [ Time Frame: weeks 0, 12, 52 ]

6.  Primary:   Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Time to Maximum Plasma Concentration(Tmax)   [ Time Frame: weeks 0, 12, 52 ]

7.  Secondary:   Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)   [ Time Frame: weeks 0, 78 ]

8.  Secondary:   Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey   [ Time Frame: weeks 0, 78 ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Genzyme Medical Information
Organization: Genzyme Corporation
phone: 800-745-4447


No publications provided by Genzyme, a Sanofi Company

Publications automatically indexed to this study:

Responsible Party: Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier: NCT00158600     History of Changes
Other Study ID Numbers: AGLU02704, 2005-002759-42
Study First Received: September 8, 2005
Results First Received: June 24, 2010
Last Updated: June 24, 2010
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Netherlands: College ter Beoordeling van Geneesmiddelen Medicines Evaluation Board (CBGMEB)