Safety and Efficacy Evaluation of Repeat neoGAA Dosing in Late Onset Pompe Disease Patients.

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01898364
• Collaborator: (none)
• Enrollment: 24
• Locations: 17
• Arms: 6
• Duration (Months): 19.1
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Primary Objective:

To evaluate the safety and tolerability of neoGAA in treatment naïve and alglucosidase alfa treated late-onset Pompe disease patients.

Secondary Objective:

To evaluate the pharmacokinetics, pharmacodynamics of neoGAA in treatment naïve and alglucosidase alfa treated late-onset Pompe disease patients.

To evaluate the effect of neoGAA on exploratory efficacy endpoints in treatment naïve and alglucosidase alfa treated late-onset Pompe disease patients.

Condition or Disease	Intervention/Treatment	Phase
Pompe Disease; Glycogen Storage Disease Type II (GSD II); Acid Maltase Deficiency	Drug: GZ402666	Phase 1

Detailed Description

Screening: within 90 days Period of treatment: 24 weeks (including 13 bi-weekly infusions) Post treatment evaluation visit: 2 weeks after last neoGAA infusion (at Week 27) End of study visit: 4 weeks after last neoGAA infusion (at Week 29) Total duration: approximately 41 weeks

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multicenter, Multinational, Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of Repeated Biweekly Infusions of neoGAA in naïve and Alglucosidase Alfa Treated Late-onset Pompe Disease Patients.
• Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GZ402666 (neoGAA) Group 1 - 5 mg Intravenous infusion of 5mg neoGAA to treatment naïve late onset Pompe disease patients once every other week for a total of 24 weeks	Drug: GZ402666; Pharmaceutical form:lyophilized powder reconstituted for infusion Route of administration: intravenous
Experimental: GZ402666 (neoGAA) Group 1 - 10 mg Intravenous infusion of 10mg neoGAA to treatment naïve late onset Pompe disease patients once every other week for a total of 24 weeks.	Drug: GZ402666; Pharmaceutical form:lyophilized powder reconstituted for infusion Route of administration: intravenous
Experimental: GZ402666 (neoGAA) Group 1 - 20 mg Intravenous infusion of 20mg neoGAA to treatment naïve late onset Pompe disease patients once every other week for a total of 24 weeks.	Drug: GZ402666; Pharmaceutical form:lyophilized powder reconstituted for infusion Route of administration: intravenous
Experimental: GZ402666 (neoGAA) Group 2 - 5 mg Intravenous infusion of 5mg neoGAA once every other week for a total of 24 weeks to late onset Pompe disease patients previously treated with alglucoside alfa.	Drug: GZ402666; Pharmaceutical form:lyophilized powder reconstituted for infusion Route of administration: intravenous
Experimental: GZ402666 (neoGAA) Group 2 - 10 mg Intravenous infusion of 10mg neoGAA once every other week for a total of 24 weeks to late onset Pompe disease patients previously treated with alglucoside alfa.	Drug: GZ402666; Pharmaceutical form:lyophilized powder reconstituted for infusion Route of administration: intravenous
Experimental: GZ402666 (neoGAA) Group 2 - 20 mg Intravenous infusion of 20mg neoGAA once every other week for a total of 24 weeks to late onset Pompe disease patients previously treated with alglucoside alfa.	Drug: GZ402666; Pharmaceutical form:lyophilized powder reconstituted for infusion Route of administration: intravenous

Outcome Measures

Primary Outcome Measures

1. Adverse events [screening/baseline to Week 25]

2. Laboratory assessments including hematology, biochemistry and urinalysis [screening/baseline to Week 25]

3. Vital signs [screening/baseline to Week 25]

Secondary Outcome Measures

1. Electrocardiogram [screening/baseline, Week 1, Week 13, Week 25]

2. Immunogenicity assessments [screening/baseline to Week 29]

3. Cmax [Week 1, Week 13, Week 25]

4. AUC [Week 1, Week 13, Week 25]

5. t1/2 [Week 1, Week 13, Week 25]

6. Skeletal muscle glycogen content [screening/baseline, Week 27]

7. Skeletal muscle magnetic resonance images for qualitative and quantitative muscle degenerative assessments. [screening/baseline, Week 27]

8. Urinary Hex4 [screening/baseline to Week 25]

9. Functional assessments including 6 Minute Walk Test (6MWT) [screening/baseline, Week 13, Week 25]

   Functional Assessment includes - pulmonary function testing (PFT) endpoints, Gait, Stair, Gower's Maneuver, Chair (GSGC), Gross Motor Function Measure-88 (GMFM-88), Quick Motor Function Test (QMFT), hand-held dynamometer testing, Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL)

10. Quality of life assessments [screening/baseline, Week 13, Week 25]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria :

For both Group 1 and Group 2:

• Male or female patients with confirmed acid α-glucosidase (GAA) enzyme deficiency from any tissue source and/or confirmed GAA gene mutation and without known cardiac hypertrophy.

• Patient willing and able to provide signed informed consent

• Patient is able to ambulate 50 meters (approximately 160 feet) without stopping and without an assistive device. Use of assistive device for community ambulation is appropriate.

• Patient has a forced vital capacity (FVC) in upright position of ≥50% predicted.

• The patient, if female and of childbearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin (β-hCG)] at baseline.

Group 2 patients only:

• The patient has been previously treated with alglucosidase alfa for at least 9 months.

Exclusion criteria:

For both Group 1 and Group 2:

• Patient is wheelchair dependent.

• Patient requires invasive-ventilation (non-invasive ventilation is allowed).

• Patient is participating in another clinical study using investigational treatment.

• Patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study.

• Patient has clinically significant organic disease (with the exception of symptoms relating to Pompe disease), including clinically significant cardiovascular, hepatic, pulmonary, neurologic, or renal disease, or other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, precludes participation in the study or potentially decreases survival.

• Patient cannot submit to MRI examination because of a formal contraindication such as a pacemaker, implanted ferromagnetic metals, anxiety disorder, etc.

Group 1 only:

• Patient has had previous treatment with alglucosidase alfa or any other enzyme replacement therapy (ERT) for Pompe disease.

Group 2 only:

• Patient has a high risk for a severe allergic reaction to neoGAA (i.e. previous moderate to severe anaphylactic reaction to alglucosidase alfa and/or patient has immunoglobulin (Ig) E antibodies to alglucosidase alfa, and/or a history of sustained high immunoglobulin G (IgG) antibody titers to alglucosidase alfa that in the opinion of the investigator suggest a high risk for an allergic reaction to neoGAA).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840006	Phoenix	Arizona	United States	85013
2	Investigational Site Number 840010	Jacksonville	Florida	United States	32209
3	Investigational Site Number 840001	Kansas City	Kansas	United States	66160-7321
4	Investigational Site Number 840008	St Louis	Missouri	United States	63110
5	Investigational Site Number 840002	Durham	North Carolina	United States	27710
6	Investigational Site Number 840009	Dallas	Texas	United States	75390
7	Investigational Site Number 840003	Fairfax	Virginia	United States	22030
8	Investigational Site Number 056001	Leuven		Belgium	3000
9	Investigational Site Number 208001	København Ø		Denmark	2100
10	Investigational Site Number 250001	Marseille		France	13385
11	Investigational Site Number 250003	Nice		France	06012
12	Investigational Site Number 250002	Paris		France	75013
13	Investigational Site Number 276003	Mainz		Germany	55131
14	Investigational Site Number 276001	München		Germany	80336
15	Investigational Site Number 276002	Münster		Germany	48149
16	Investigational Site Number 528001	Rotterdam		Netherlands	3015 GJ
17	Investigational Site Number 826003	Newcastle Upon Tyne		United Kingdom	NE1 4LP

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01898364
• Other Study ID Numbers: TDR12857; 2012-004167-42; U1111-1144-7725
• First Posted: Jul 12, 2013
• Last Update Posted: Mar 11, 2015
• Last Verified: Mar 1, 2015

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

Study Results

No Results Posted as of Mar 11, 2015