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

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.

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.

Study Overview

• Status: Completed
• Conditions: Pompe Disease; Glycogen Storage Disease Type II (GSD II); Acid Maltase Deficiency
• Intervention / Treatment: Drug: GZ402666

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Investigational Site Number 056001
• Denmark
  • København Ø, Denmark, 2100
    • Investigational Site Number 208001
• France
  • Marseille, France, 13385
    • Investigational Site Number 250001
  • Nice, France, 06012
    • Investigational Site Number 250003
  • Paris, France, 75013
    • Investigational Site Number 250002
• Germany
  • Mainz, Germany, 55131
    • Investigational Site Number 276003
  • München, Germany, 80336
    • Investigational Site Number 276001
  • Münster, Germany, 48149
    • Investigational Site Number 276002
• Netherlands
  • Rotterdam, Netherlands, 3015 GJ
    • Investigational Site Number 528001
• United Kingdom
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • Investigational Site Number 826003
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Investigational Site Number 840006
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Investigational Site Number 840010
  • Kansas
    • Kansas City, Kansas, United States, 66160-7321
      • Investigational Site Number 840001
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Investigational Site Number 840008
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Investigational Site Number 840002
  • Texas
    • Dallas, Texas, United States, 75390
      • Investigational Site Number 840009
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Investigational Site Number 840003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse events	screening/baseline to Week 25
Laboratory assessments including hematology, biochemistry and urinalysis	screening/baseline to Week 25
Vital signs	screening/baseline to Week 25

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrocardiogram		screening/baseline, Week 1, Week 13, Week 25
Immunogenicity assessments		screening/baseline to Week 29
Cmax		Week 1, Week 13, Week 25
AUC		Week 1, Week 13, Week 25
t1/2		Week 1, Week 13, Week 25
Skeletal muscle glycogen content		screening/baseline, Week 27
Skeletal muscle magnetic resonance images for qualitative and quantitative muscle degenerative assessments.		screening/baseline, Week 27
Urinary Hex4		screening/baseline to Week 25
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
Quality of life assessments		screening/baseline, Week 13, Week 25

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2013
• Primary Completion (Actual): February 25, 2015
• Study Completion (Actual): February 25, 2015

Study Registration Dates

• First Submitted: July 2, 2013
• First Submitted That Met QC Criteria: July 9, 2013
• First Posted (Estimate): July 12, 2013

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease Type II; Glycogen Storage Disease
• Other Study ID Numbers: TDR12857; 2012-004167-42 (EudraCT Number); U1111-1144-7725 (Other Identifier: (UTN))