An Exploratory, Open-Label Study of the Safety and Efficacy of High Dose or High Dosing Frequency Myozyme® (alglucosidase alfa) Treatment in Patients with Pompe Disease Who Do Not Have an Optimal Response to the Standard Dose Regimen

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2015-000582-31-Outside-EU/EEA
• Date of registration: 15/04/2015
• Prospective Registration: Yes
• Primary sponsor: Genzyme Corporation Inc
• Public title: An Exploratory, Open-Label Study of the Safety and Efficacy of High Dose or High Dosing Frequency Myozyme® (alglucosidase alfa) Treatment in Patients with Pompe Disease Who Do Not Have an Optimal Response to the Standard Dose Regimen
• Scientific title: An Exploratory, Open-Label Study of the Safety and Efficacy of High Dose or High Dosing Frequency Myozyme® (alglucosidase alfa) Treatment in Patients with Pompe Disease Who Do Not Have an Optimal Response to the Standard Dose Regimen
• Target sample size: 14
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000582-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Canada, United States

Contacts

• Name: Trial Transparency Team
• Affiliation: Genzyme, a Sanofi Company

• Name: Trial Transparency Team
• Affiliation: Genzyme, a Sanofi Company

Key inclusion & exclusion criteria

Inclusion criteria:
(1) the patient or the patient’s legal guardian(s) must provide written informed
consent prior to any study-related procedures being performed; (2) the patient must have a clinical diagnosis of Pompe disease as defined by documented GAA deficiency (deficient endogenous GAA activity) in skin fibroblasts or blood; (3) the patient must have been compliant with the standard dosing regimen of Myozyme (20 mg/kg qow) for a minimum of 6 months prior to study entry; and (4) 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 beginning Myozyme treatment:

Cardiac
Left Ventricular Mass (LVM) Z-score = 6 or LVM Index = 150 g/m2 after a minimum of 6 months of treatment with Myozyme, OR

Respiratory
New development of respiratory failure requiring the use of ventilatory assistance (invasive or noninvasive) after a minimum of 6 months of treatment with Myozyme. Ventilatory assistance must have been required for at least 4 weeks prior to study enrollment, OR

Motor Skills
For patients < or equal to 2 years of age at study entry, failure to acquire at least 2 new gross motor milestones after a minimum of 6 months of treatment with Myozyme, e.g.:
1. Turning head side to side (supine)
2. Grasping small objects with hands
3. Transferring objects from hand to hand
4. Holding head upright with body supported
5. Rolling (supine to prone or prone to supine)
6. Sitting (supported or unsupported)
7. Walking (with support, i.e., cruising, or independently)
8. Walking up stairs (with assistance or independently)

OR
For patients > 2 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 treatment with Myozyme, 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 treatment with Myozyme, OR

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 treatment with Myozyme.






Are the trial subjects under 18? yes
Number of subjects for this age range: 13
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients will be excluded from this study if they meet any of the following exclusion criteria (1) any medical condition which, in the opinion of the Investigator, could interfere with treatment or evaluation of safety and/or efficacy of Myozyme; (2) the patient has major congenital abnormality; (3) 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; or (4) the patient is pregnant or lactating.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Pompe disease (acid alpha-glucosidase deficiency)
MedDRA version: 17.1 Level: LLT Classification code 10036143 Term: Pompe's disease System Organ Class: 100000004850

Intervention(s)

Trade Name: Myozyme 50 mg powder for concentrate for solution for infusion

Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: ALGLUCOSIDASE ALFA
CAS Number: 420784-05-0
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 1 and 2 : Baseline, Week 52
3 : Day 1 up to Week 52

Main Objective: 1. Evaluate the safety and efficacy of alternate alglucosidase alfa dosing regimens
2. Evaluate differences in efficacy in the 2 dosing arms

Secondary Objective: 1. Effect of increases in alglucosidase alfa dose or dose frequency on cardiac pathophysiology as measured by Left Ventricular Mass and Left Ventricular Mass Index
2. Effect of increases in alglucosidase alfa dose or dose frequency on respiratory function as measured by ventilator use diary
3. Effect of increases in alglucosidase alfa dose or dose frequency on proximal and distal muscle strength as measured by manual muscle testing in patients = 8 years of age
4. Effect of increases in alglucosidase alfa dose or dose frequency on gross motor function as measured by Gross Motor Function Measure
5. Effect of increases in alglucosidase alfa dose or dose frequency on functional status as measured by the Pompe Pediatric Evaluation of Disability Index
6. Effect of increases in alglucosidase alfa dose or dose frequency on health-related quality of life as measured by the Physical Component Summary (PCS) score of the Medical Outcomes Study (MOS) SF-36 for patients =14 years of age.

Primary end point(s): 1. Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Respiratory Decline on Standard Treatment
2. Participants' Efficacy Response During the Treatment Period as Compared to Baseline for Participants With Motor Function Decline on Standard Treatment
3. Summary of Participants Reporting Treatment-Emergent Adverse Events During the Treatment Period

Secondary Outcome(s)

Secondary end point(s): 1. Baseline Values for Left Ventricular Mass (LVM) Z-Scores
2. Change From Baseline in Left Ventricular Mass (LVM) Z-Score at Week 52
3. Baseline Values for Left Ventricular Mass Index (LVMI)
4. Change From Baseline in Left Ventricular Mass Index (LVMI) at Week 52
5. Change From Baseline in Ventilator Use at Last Assessment (Approximately Week 52)
6. Change From Baseline in Body Strength Measured by the Manual Muscle Testing (MMT) Total Score at Week 52
7. Baseline Values of Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results
8. Change From Baseline in Raw Scores for Gross Motor Function Measure 66 (GMFM-66) Results at Week 52
9. Baseline Values in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI)
10. Change From Baseline in Mobility as Measured by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) at Week 52
11. Baseline Values for Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36)
12. Change From Baseline in Normative Physical Component Summary of Medical Outcomes Study Short Form Health Survey (SF-36) at Week 52

Timepoint(s) of evaluation of this end point: Day 0
1-3-7-9-11

Baseline, Week 52
2-4-5-6-8-10-12

Secondary ID(s)

AGLU3306

Source(s) of Monetary Support

Genzyme Corporation Inc