Avalglucosidase Alfa Extension Study (NEO-EXT)

• ClinicalTrials.gov Identifier: NCT02032524
• Recruitment Status: Completed
• First Posted: January 10, 2014
• Last Update Posted: December 15, 2022
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Tracking Information

• First Submitted Date: December 4, 2013
• First Posted Date: January 10, 2014
• Last Update Posted Date: December 15, 2022
• Actual Study Start Date: February 27, 2014
• Actual Primary Completion Date: December 12, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 16, 2019)

• Assessment of adverse events (AEs) and treatment-emergent adverse events (TEAEs), including infusion-associated reactions (IARs) and deaths [ Time Frame: screening/baseline until approximately Year 8 ]
• Laboratory assessments including hematology, biochemistry and urinalysis [ Time Frame: Monthly, from baseline until Year 3 then quarterly until approximately Year 8 ]
• Vital signs [ Time Frame: screening/baseline until approximately Year 8 ]

Original Primary Outcome Measures (submitted: January 8, 2014)

• Assessment of adverse events (AEs) and treatment-emergent adverse events (TEAEs) [ Time Frame: screening/baseline until year 6 ]
• Laboratory assessments including hematology, biochemistry and urinalysis [ Time Frame: Monthly, from baseline until year 6 ]
• Vital signs [ Time Frame: screening/baseline until year 6 ]

Current Secondary Outcome Measures (submitted: December 16, 2019)

• Electrocardiogram [ Time Frame: every 6 months, from baseline until approximately Year 8 ]
• Anti-avalglucosidase alfa antibodies, and neutralizing antibody formation in anti-avalglucosidase alfa positive patients; anti-alglucosidase alfa IgG antibodies [ Time Frame: monthly, from baseline up to 6 months, then every 3 months until approximately Year 8; every 6 months from baseline until approximately Year 8 ]
• Cmax (maximal concentration of the compound in the blood) [ Time Frame: at 6 months, then yearly until approximately Year 8 ]
• AUC (area under the curve, relates to the quantity of compound that produces an effect) [ Time Frame: at 6 months, then yearly until approximately Year 8 ]
• t1/2 (half-life, which is the time needed to eliminate half of the compound) [ Time Frame: at 6 months, then yearly until approximately Year 8 ]
• Skeletal muscle glycogen content [ Time Frame: every 2 years, from baseline until approximately Year 8 ]
• Skeletal muscle magnetic resonance images for qualitative and quantitative muscle degenerative assessments [ Time Frame: every 2 years, from baseline until approximately Year 8 ]
• Urinary Hex4 [ Time Frame: at 6 months, then yearly until approximately Year 8 ]
• Plasma analyses of circulating RNA [ Time Frame: at 6 months, then yearly until approximately Year 8 ]
• Serum analyses of skeletal muscle RNA expression [ Time Frame: at 6 months, then yearly until approximately Year 8 ]

Original Secondary Outcome Measures (submitted: January 8, 2014)

• Electrocardiogram [ Time Frame: every 6 months, from baseline until year 6 ]
• Immunogenicity assessments (anti-neoGAA immunoglobulin G (IgG) antibodies, neutralizing antibody formation in IgG seropositive patients, and anti-alglucosidase alfa IgG antibodies) [ Time Frame: every 6 months, from baseline until year 6 ]
• Cmax [ Time Frame: at 6 months, then yearly until year 6 ]
• AUC [ Time Frame: at 6 months, then yearly until year 6 ]
• t1/2 [ Time Frame: at 6 months, then yearly until year 6 ]
• Skeletal muscle glycogen content [ Time Frame: every 2 years, from baseline until year 6 ]
• Skeletal muscle magnetic resonance images for qualitative and quantitative muscle degenerative assessments [ Time Frame: every 2 years, from baseline until year 6 ]
• Urinary Hex4 [ Time Frame: every 6 months, from baseline until year 6 ]
• plasma analyses of circulating mRNA and micro RNA [ Time Frame: every 6 months, from baseline until year 6 ]
• serum analyses of skeletal muscle RNA expression [ Time Frame: every 2 years, from baseline until year 6 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Avalglucosidase Alfa Extension Study
• Official Title: An Open-Label, Multicenter, Multinational Extension Study Of The Long-Term Safety And Pharmacokinetics Of Repeated Biweekly Infusions Of Avalglucosidase Alfa In Patients With Pompe Disease

Brief Summary

Primary Objective:

Long-term safety and pharmacokinetics (PK) of avalglucosidase alfa

Secondary Objective:

Long-term effect of avalglucosidase alfa on pharmacodynamic and exploratory efficacy variables

Detailed Description

The duration of the study will be 6 years from the date the first patient enters the study. Each patient will continue with the study until the patient withdraws, the Investigator withdraws the patient, or the Sponsor terminates the study.

An additional follow-up phase will begin after the patient's last planned visit in the 6-year study and last until avalglucosidase alfa is approved in the patient's country for all patients.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Glycogen Storage Disease Type II Pompe Disease

Intervention

Drug: GZ402666

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

Other Name: avalglucosidase alfa

Study Arms

Experimental: Avalglucosidase alfa

administered intravenously every 2 weeks

Intervention: Drug: GZ402666

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 3, 2021): 19
• Original Estimated Enrollment (submitted: January 8, 2014): 18
• Actual Study Completion Date: December 12, 2022
• Actual Primary Completion Date: December 12, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

Patients with Pompe disease who previously completed a an avalglucosidase study.

The patient and/or their parent/legal guardian is willing and able to provide signed informed consent, and the patient, if <18 years of age, is willing to provide assent if deemed able to do so.

The patient (and patient's legal guardian if patient is <18 years of age) must have the ability to comply with the clinical protocol.

The patient, if female and of childbearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin] at baseline.

Exclusion criteria:

The patient is concurrently participating in another clinical study using investigational treatment.

The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study.

The 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.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Denmark, France, Germany, Netherlands, United Kingdom, United States

Administrative Information

• NCT Number: NCT02032524
• Other Study ID Numbers: LTS13769; U1111-1147-3439 ( Other Identifier: UTN )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

• Current Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
• Original Responsible Party: Sanofi
• Current Study Sponsor: Genzyme, a Sanofi Company
• Original Study Sponsor: Sanofi
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: December 2022