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

NCT01898364 | Completed Phase 1 DMC

• 3 other identifiers: TDR128572012-004167-42U1111-1144-7725
• Study Type: interventional
• Target: 24
• Locations: 7 countries
• Sites: 17

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• 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

Study Arms (6)

GZ402666 (neoGAA) Group 1 - 5 mg

EXPERIMENTAL

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

GZ402666 (neoGAA) Group 1 - 10 mg

EXPERIMENTAL

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

GZ402666 (neoGAA) Group 1 - 20 mg

EXPERIMENTAL

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

GZ402666 (neoGAA) Group 2 - 5 mg

EXPERIMENTAL

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

GZ402666 (neoGAA) Group 2 - 10 mg

EXPERIMENTAL

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

GZ402666 (neoGAA) Group 2 - 20 mg

EXPERIMENTAL

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

Interventions

GZ402666 DRUG

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

GZ402666 (neoGAA) Group 1 - 10 mg; GZ402666 (neoGAA) Group 1 - 20 mg; GZ402666 (neoGAA) Group 1 - 5 mg; GZ402666 (neoGAA) Group 2 - 10 mg; GZ402666 (neoGAA) Group 2 - 20 mg; GZ402666 (neoGAA) Group 2 - 5 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (17)

Investigational Site Number 840006

Phoenix, Arizona, 85013, United States

Location

Investigational Site Number 840010

Jacksonville, Florida, 32209, United States

Location

Investigational Site Number 840001

Kansas City, Kansas, 66160-7321, United States

Location

Investigational Site Number 840008

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 840002

Durham, North Carolina, 27710, United States

Location

Investigational Site Number 840009

Dallas, Texas, 75390, United States

Location

Investigational Site Number 840003

Fairfax, Virginia, 22030, United States

Location

Investigational Site Number 056001

Leuven, 3000, Belgium

Location

Investigational Site Number 208001

København Ø, 2100, Denmark

Location

Investigational Site Number 250001

Marseille, 13385, France

Location

Investigational Site Number 250003

Nice, 06012, France

Location

Investigational Site Number 250002

Paris, 75013, France

Location

Investigational Site Number 276003

Mainz, 55131, Germany

Location

Investigational Site Number 276001

München, 80336, Germany

Location

Investigational Site Number 276002

Münster, 48149, Germany

Location

Investigational Site Number 528001

Rotterdam, 3015 GJ, Netherlands

Location

Investigational Site Number 826003

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (1)

• Dimachkie MM, Barohn RJ, Byrne B, Goker-Alpan O, Kishnani PS, Ladha S, Laforet P, Mengel KE, Pena LDM, Sacconi S, Straub V, Trivedi J, Van Damme P, van der Ploeg AT, Vissing J, Young P, Haack KA, Foster M, Gilbert JM, Miossec P, Vitse O, Zhou T, Schoser B; NEO-EXT investigators. Long-term Safety and Efficacy of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease. Neurology. 2022 Aug 1;99(5):e536-e548. doi: 10.1212/WNL.0000000000200746.

  PMID: 35618441 DERIVED

MeSH Terms

Conditions

Glycogen Storage Disease Type II

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

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2013
• First Posted: July 12, 2013
• Study Start: August 19, 2013
• Primary Completion: February 25, 2015
• Study Completion: February 25, 2015
• Last Updated: March 23, 2023

Record last verified: 2023-03

Locations

NL (1); BE (1); FR (3); US (7); DE (3); GB (1); DK (1)