High Dose or High Dose Frequency Study of Alglucosidase Alfa

NCT00483379 | Completed Phase 4 Results DMC

• 1 other identifier: AGLU03306
• Study Type: interventional
• Target: 13
• Locations: 3 countries
• Sites: 11

Brief Summary

Pompe disease (also known as glycogen storage disease Type II) is caused by a deficiency of a critical enzyme in the body called acid alpha-glucosidase (GAA). Normally, GAA is used by the body's cells to break down glycogen (a stored form of sugar) within specialized structures called lysosomes. In patients with Pompe disease, an excessive amount of glycogen accumulates and is stored in various tissues, especially heart and skeletal muscle, which prevents their normal function. The objective of this exploratory study is to evaluate the safety and efficacy of alternative dosing regimens of alglucosidase alfa in patients with Pompe disease who have not demonstrated an optimal response to the standard dosing regimen of 20 mg/kg every other week after a minimum of 6 months treatment immediately prior to study entry.

Conditions

Pompe Disease; Glycogen Storage Disease Type II (GSD-II); Glycogenesis 2 Acid Maltase Deficiency

Outcome Measures

Primary Outcomes (3)

• Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline 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; 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.

  Baseline, Week 52

• Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline 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.

  Baseline, Week 52

• Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period

  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.

  Day 1 up to Week 52

Secondary Outcomes (12)

• Baseline Values for Left Ventricular Mass (LVM) Z-Scores

  Day 0

• Change From Baseline in Left Ventricular Mass (LVM) Z-Score at Week 52

  Baseline, Week 52

• Baseline Values for Left Ventricular Mass Index (LVMI)

  Day 0

• Change From Baseline in Left Ventricular Mass Index (LVMI) at Week 52

  Baseline, Week 52

• Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52)

  Baseline, approximately Week 52

Study Arms (2)

alglucosidase alfa 20 mg/kg every week

EXPERIMENTAL

Participants were treated with alglucosidase alfa 20 mg/kg every week for 52 weeks. This was the 'frequent dose' arm.

Biological: alglucosidase alfa

alglucosidase alfa 40 mg/kg every other week

EXPERIMENTAL

Participants were treated with alglucosidase alfa 40 mg/kg every other week for 52 weeks. This was the 'high dose' arm.

Biological: alglucosidase alfa

Interventions

alglucosidase alfa BIOLOGICAL

intravenous infusion

Also known as: Recombinant human acid glucosidase, Myozyme

alglucosidase alfa 20 mg/kg every week; alglucosidase alfa 40 mg/kg every other week

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient or patient's legal guardian must provide signed, informed consent prior to performing any study-related procedures;
• The patient must have a clinical diagnosis of Pompe disease as defined by documented GAA deficiency in skin fibroblasts or blood;
• The patient must have been compliant with the standard dosing regimen of alglucosidase alfa (20 mg/kg every other week) for a minimum of 6 months immediately prior to study entry
• The patient must have clinical decline or sub-optimal improvement in at least one of the following parameters as compared to their condition prior to the beginning alglucosidase alfa treatment:
• Cardiac: Left Ventricular Mass (LVM) Z-score ≥6 or LVM index ≥150 g/m2 after a minimum of 6 months of regular treatment with alglucosidase alfa; OR
• Respiratory: New development of respiratory failure requiring the use of ventilatory assistance (invasive or non-invasive) after a minimum of 6 months of regular treatment with alglucosidase alfa. Ventilatory assistance must have been required for at least 4 weeks prior to study enrollment; OR
• Motor Skills:
• For patients ≤ 2 years of age at study entry, failure to acquire at least 2 new gross motor milestones after a minimum of 6 months of regular treatment with alglucosidase alfa; OR
• For patients \> 2 years of age at study entry, worsening of proximal upper extremity muscle weakness as determined by the Investigator through loss of functional use of the upper extremities after a minimum of 6 months of regular treatment with alglucosidase alfa, OR
• For patients \> 8 years of age at study entry, worsening of proximal upper extremity muscle weakness as determined by the Investigator through longitudinal assessments of manual muscle testing after a minimum of 6 months of regular treatment with alglucosidase alfa, OR
• For patients previously ambulatory, progression to use of an assistive device for ambulation due to worsening of proximal lower extremity muscle weakness after a minimum of 6 months of regular treatment with alglucosidase alfa.

You may not qualify if:

• For patients \< 18 years of age, negative Cross-Reactive Immunologic Material (CRIM) assay result (added in protocol amendment #2);
• Any medical condition which, in the opinion of the Investigator, could interfere with treatment or evaluation of safety and/or efficacy of alglucosidase alfa;
• The patient is not currently receiving alglucosidase alfa;
• The patient has major congenital abnormality;
• The patient has used any investigational product (other than alglucosidase alfa in those regions where the product is not commercially available) within 30 days prior to study enrollment;
• The patient is pregnant or lactating.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (11)

Unknown Facility

Birmingham, Alabama, United States

Location

Unknown Facility

Stanford, California, United States

Location

Unknown Facility

Washington D.C., District of Columbia, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Kansas City, Kansas, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Grand Rapids, Michigan, United States

Location

Unknown Facility

Glenn Falls, New York, United States

Location

Unknown Facility

Durham, North Carolina, United States

Location

Unknown Facility

Parkville Victoria, Australia

Location

Unknown Facility

Calgary, Alberta, Canada

Location

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Interventions

GAA protein, human

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

This small exploratory study lacked a parallel control arm at the standard dose for a longer period; decline in respiratory or motor function prior to study was not collected systematically, thus change from baseline observations are inconclusive.

Results Point of Contact

• Title: Genzyme Medical Information
• Organization: Genzyme Corporation

800-745-4447

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2007
• First Posted: June 7, 2007
• Study Start: May 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: July 1, 2010
• Last Updated: March 7, 2014
• Results First Posted: April 22, 2011

Record last verified: 2014-02

Locations

AU (1); CA (1); US (9)