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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01898364
First received: July 2, 2013
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Pompe Disease
Glycogen Storage Disease Type II (GSD II)
Acid Maltase Deficiency
Drug: GZ402666
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Adverse events [ Time Frame: screening/baseline to Week 25 ] [ Designated as safety issue: Yes ]
  • Laboratory assessments including hematology, biochemistry and urinalysis [ Time Frame: screening/baseline to Week 25 ] [ Designated as safety issue: Yes ]
  • Vital signs [ Time Frame: screening/baseline to Week 25 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Electrocardiogram [ Time Frame: screening/baseline, Week 1, Week 13, Week 25 ] [ Designated as safety issue: Yes ]
  • Immunogenicity assessments [ Time Frame: screening/baseline to Week 29 ] [ Designated as safety issue: Yes ]
  • Cmax [ Time Frame: Week 1, Week 13, Week 25 ] [ Designated as safety issue: No ]
  • AUC [ Time Frame: Week 1, Week 13, Week 25 ] [ Designated as safety issue: No ]
  • t1/2 [ Time Frame: Week 1, Week 13, Week 25 ] [ Designated as safety issue: No ]
  • Skeletal muscle glycogen content [ Time Frame: screening/baseline, Week 27 ] [ Designated as safety issue: No ]
  • Skeletal muscle magnetic resonance images for qualitative and quantitative muscle degenerative assessments. [ Time Frame: screening/baseline, Week 27 ] [ Designated as safety issue: No ]
  • Urinary Hex4 [ Time Frame: screening/baseline to Week 25 ] [ Designated as safety issue: No ]
  • Functional assessments including 6 Minute Walk Test (6MWT) [ Time Frame: screening/baseline, Week 13, Week 25 ] [ Designated as safety issue: No ]
    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)

  • Quality of life assessments [ Time Frame: screening/baseline, Week 13, Week 25 ] [ Designated as safety issue: No ]

Estimated Enrollment: 21
Study Start Date: July 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01898364

Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

Locations
United States, Arizona
Investigational Site Number 840006 Recruiting
Phoenix, Arizona, United States, 85013
United States, Florida
Investigational Site Number 840010 Recruiting
Jacksonville, Florida, United States, 32209
United States, Kansas
Investigational Site Number 840001 Recruiting
Kansas City, Kansas, United States, 66160-7321
United States, Missouri
Investigational Site Number 840008 Recruiting
St Louis, Missouri, United States, 63110
United States, North Carolina
Investigational Site Number 840002 Recruiting
Durham, North Carolina, United States, 27710
United States, Ohio
Investigational Site Number 840005 Recruiting
Columbus, Ohio, United States, 43210
United States, Texas
Investigational Site Number 840009 Recruiting
Dallas, Texas, United States, 75390
United States, Virginia
Investigational Site Number 840003 Recruiting
Fairfax, Virginia, United States, 22030
Belgium
Investigational Site Number 056001 Recruiting
Leuven, Belgium, 3000
Denmark
Investigational Site Number 208001 Recruiting
København Ø, Denmark, 2100
France
Investigational Site Number 250001 Recruiting
Marseille, France, 13385
Investigational Site Number 250003 Recruiting
Nice, France, 06012
Investigational Site Number 250002 Recruiting
Paris, France, 75013
Germany
Investigational Site Number 276003 Recruiting
Mainz, Germany, 55131
Investigational Site Number 276001 Recruiting
München, Germany, 80336
Investigational Site Number 276002 Recruiting
Münster, Germany, 48149
Italy
Investigational Site Number 380001 Recruiting
Messina, Italy, 98124
Netherlands
Investigational Site Number 528001 Recruiting
Rotterdam, Netherlands, 3015 GJ
United Kingdom
Investigational Site Number 826003 Recruiting
Newcastle Upon Tyne, United Kingdom, NE1 4LP
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01898364     History of Changes
Other Study ID Numbers: TDR12857, 2012-004167-42, U1111-1144-7725
Study First Received: July 2, 2013
Last Updated: July 21, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Glycogen Storage Disease Type II
Glycogen Storage Disease
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
Carbohydrate Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on July 29, 2014