Clinical trial NCT02032524: 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 (neoGAA, GZ402666) in Patients With Pompe Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glycogen Storage Disease Type II Pompe Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2014-01-10
Enrollment: 19
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objective:

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

Secondary Objective:

Long-term effect of avalglucosidase alfa on pharmacodynamic variables

Detailed description: The planned duration of the study for each participant was initially 6 years. Each participant continued with the study until the participant withdrew, the Investigator withdrew the participant, or the Sponsor terminated the study. An additional follow-up phase began after the participant has completed the 6-year study period, and lasted until avalglucosidase alfa was approved in the participant's country, except in the United Kingdom (UK), Germany and Denmark, where the duration of the additional follow-up phase was up to the approval in the country or limited to a maximum of 2 years, whichever occurred first (ie, for participants in the UK, Germany and Denmark, the total study duration per participant was 8 years at the maximum including the initial 6-year period and the additional 2-year follow-up).

Eligibility criteria: Inclusion criteria:

Participants with Pompe disease who previously completed an avalglucosidase study.

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

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

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

Exclusion criteria:

The participant was concurrently participating in another clinical study using investigational treatment.

The participant, in the opinion of the Investigator, was unable to adhere to the requirements of the study.

The participant had 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, precluded participation in the study or potentially decreases survival.

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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Infusion Associated Reactions (IARs) and Deaths
timeFrame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
measure: Number of Participants With Clinically Significant Physical Examination Abnormalities
timeFrame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
measure: Number of Participants With Potentially Clinically Significant Abnormalities in Biochemistry
timeFrame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
measure: Number of Participants With Potentially Clinically Significant Abnormalities in Hematology
timeFrame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
measure: Change From Baseline in Urine BUN up to Last IMP Administration
timeFrame: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
measure: Change From Baseline in Urine Hyaline Casts up to Last IMP Administration
timeFrame: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
measure: Change From Baseline in Urine Leukocytes [White Blood Cell (WBC)] up to Last IMP Administration
timeFrame: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
measure: Change From Baseline in Urine Specific Gravity up to Last IMP Administration
timeFrame: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
measure: Change From Baseline in Urine pH up to Last IMP Administration
timeFrame: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
measure: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities
timeFrame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
measure: Number of Participants With Body Weight Increased/Decreased
timeFrame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
measure: Number of Participants With Potentially Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities
timeFrame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
measure: Number of Participants With Antidrug Antibodies (ADA) Status, Positive or Negative
timeFrame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
measure: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa
timeFrame: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Real Time (AUClast) of Avalglucosidase Alfa
timeFrame: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
measure: Time Corresponding to the Last Concentration (Tlast) of Avalglucosidase Alfa
timeFrame: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
measure: Terminal Half-Life (t1/2z) of Avalglucosidase Alfa
timeFrame: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
measure: Apparent Total Body Clearance Steady-State (CLss) of Avalglucosidase Alfa
timeFrame: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
measure: Apparent Volume of Distribution Steady-State (Vss) of Avalglucosidase Alfa
timeFrame: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Secondary outcomes:
measure: Change From Baseline in Cross-Sectional Area (CSA) of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
timeFrame: Baseline (Day 1) and Weeks 104 and 442
measure: Change From Baseline in Dixon Fat Fraction of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
timeFrame: Baseline (Day 1) and Weeks 104 and 442
measure: Change From Baseline in Index of Real Muscle Mass (IRMM) of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
timeFrame: Baseline (Day 1) and Weeks 104 and 442
measure: Change From Baseline in T2 of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
timeFrame: Baseline (Day 1) and Weeks 104 and 442
measure: Change From Baseline in T2 With B1 of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
timeFrame: Baseline (Day 1) and Weeks 104 and 442
measure: Change From Baseline in Skeletal Muscle Biopsy Up to Week 312
timeFrame: Baseline (Day 1) and Weeks 27, 104, 208, 260 and 312
measure: Change From Baseline in Urinary Glucose Tetrasaccharide (Hex4) Level Up to Week 442
timeFrame: Baseline (Day 1) and Weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 338, 364, 390, 416 and 442
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: Cincinnati
country: United States
facility: Investigational Site Number 840011
state: Ohio
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: 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: