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

Pompe Disease Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01898364
• Other study ID #: TDR12857
• Secondary ID: 2012-004167-42U1
• Status: Completed
• Phase: Phase 1
• Start date: August 19, 2013
• Est. completion date: February 25, 2015

Study information

• Verified date: March 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: February 25, 2015
• Est. primary completion date: February 25, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

For both Group 1 and Group 2:

• Male or female patients with confirmed acid a-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 (ß-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.

Related Conditions & MeSH terms

• Acid Maltase Deficiency
• Glycogen Storage Disease
• Glycogen Storage Disease Type II
• Glycogen Storage Disease Type II (GSD II)
• Pompe Disease

Intervention

Drug:
• GZ402666
Pharmaceutical form:lyophilized powder reconstituted for infusion Route of administration: intravenous

Locations

Country	Name	City	State
Belgium	Investigational Site Number 056001	Leuven
Denmark	Investigational Site Number 208001	København Ø
France	Investigational Site Number 250001	Marseille
France	Investigational Site Number 250003	Nice
France	Investigational Site Number 250002	Paris
Germany	Investigational Site Number 276003	Mainz
Germany	Investigational Site Number 276001	München
Germany	Investigational Site Number 276002	Münster
Netherlands	Investigational Site Number 528001	Rotterdam
United Kingdom	Investigational Site Number 826003	Newcastle Upon Tyne
United States	Investigational Site Number 840009	Dallas	Texas
United States	Investigational Site Number 840002	Durham	North Carolina
United States	Investigational Site Number 840003	Fairfax	Virginia
United States	Investigational Site Number 840010	Jacksonville	Florida
United States	Investigational Site Number 840001	Kansas City	Kansas
United States	Investigational Site Number 840006	Phoenix	Arizona
United States	Investigational Site Number 840008	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Belgium,  Denmark,  France,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events		screening/baseline to Week 25
Primary	Laboratory assessments including hematology, biochemistry and urinalysis		screening/baseline to Week 25
Primary	Vital signs		screening/baseline to Week 25
Secondary	Electrocardiogram		screening/baseline, Week 1, Week 13, Week 25
Secondary	Immunogenicity assessments		screening/baseline to Week 29
Secondary	Cmax		Week 1, Week 13, Week 25
Secondary	AUC		Week 1, Week 13, Week 25
Secondary	t1/2		Week 1, Week 13, Week 25
Secondary	Skeletal muscle glycogen content		screening/baseline, Week 27
Secondary	Skeletal muscle magnetic resonance images for qualitative and quantitative muscle degenerative assessments.		screening/baseline, Week 27
Secondary	Urinary Hex4		screening/baseline to Week 25
Secondary	Functional assessments including 6 Minute Walk Test (6MWT)	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)	screening/baseline, Week 13, Week 25
Secondary	Quality of life assessments		screening/baseline, Week 13, Week 25