Clinical trial NCT01898364: Safety and Efficacy Evaluation of Repeat neoGAA Dosing in Late Onset Pompe Disease Patients.
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pompe Disease
Glycogen Storage Disease Type II (GSD II)
Acid Maltase Deficiency
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2013-07-12
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Adverse events
timeFrame: screening/baseline to Week 25
measure: Laboratory assessments including hematology, biochemistry and urinalysis
timeFrame: screening/baseline to Week 25
measure: Vital signs
timeFrame: screening/baseline to Week 25
Secondary outcomes:
measure: Electrocardiogram
timeFrame: screening/baseline, Week 1, Week 13, Week 25
measure: Immunogenicity assessments
timeFrame: screening/baseline to Week 29
measure: Cmax
timeFrame: Week 1, Week 13, Week 25
measure: AUC
timeFrame: Week 1, Week 13, Week 25
measure: t1/2
timeFrame: Week 1, Week 13, Week 25
measure: Skeletal muscle glycogen content
timeFrame: screening/baseline, Week 27
measure: Skeletal muscle magnetic resonance images for qualitative and quantitative muscle degenerative assessments.
timeFrame: screening/baseline, Week 27
measure: Urinary Hex4
timeFrame: screening/baseline to Week 25
measure: Functional assessments including 6 Minute Walk Test (6MWT)
timeFrame: screening/baseline, Week 13, Week 25
measure: Quality of life assessments
timeFrame: screening/baseline, Week 13, Week 25
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Investigational Site Number 840006
state: Arizona
city: Jacksonville
country: United States
facility: Investigational Site Number 840010
state: Florida
city: Kansas City
country: United States
facility: Investigational Site Number 840001
state: Kansas
city: Saint Louis
country: United States
facility: Investigational Site Number 840008
state: Missouri
city: Durham
country: United States
facility: Investigational Site Number 840002
state: North Carolina
city: Dallas
country: United States
facility: Investigational Site Number 840009
state: Texas
city: Fairfax
country: United States
facility: Investigational Site Number 840003
state: Virginia
city: Leuven
country: Belgium
facility: Investigational Site Number 056001
city: København Ø
country: Denmark
facility: Investigational Site Number 208001
city: Marseille
country: France
facility: Investigational Site Number 250001
city: Nice
country: France
facility: Investigational Site Number 250003
city: Paris
country: France
facility: Investigational Site Number 250002
city: Mainz
country: Germany
facility: Investigational Site Number 276003
city: München
country: Germany
facility: Investigational Site Number 276001
city: Münster
country: Germany
facility: Investigational Site Number 276002
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 528001
city: Newcastle Upon Tyne
country: United Kingdom
facility: Investigational Site Number 826003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: