Glycogen Storage Disease Type II Pompe DiseasePhase 2NEO-EXTNCT02032524

Avalglucosidase Alfa Extension Study

A Phase 2 study testing Avalglucosidase Alfa in people with Glycogen Storage Disease Type II Pompe Disease, run by Genzyme, a Sanofi Company at 17 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Primary Objective: Long-term safety and pharmacokinetics (PK) of avalglucosidase alfa Secondary Objective: Long-term effect of avalglucosidase alfa on pharmacodynamic variables Read more about this study

Who is it for?: Any age
Conditions the study is for: Glycogen Storage Disease Type II Pompe Disease
What is being tested?: Avalglucosidase Alfa
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 19 participants
Where: 17 sitesin 7 countries
Study dates: 27 Feb 2014to 12 Dec 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

17 sites in 7 countries.

Country

City, postcode or hospital

17 sites in 7 countries

United States8 sites

Investigational Site Number 840011
Cincinnati, Ohio, 45219
Investigational Site Number 840009
Dallas, Texas, 75390
Investigational Site Number 840002
Durham, North Carolina, 27710
Investigational Site Number 840003
Fairfax, Virginia, 22030
Investigational Site Number 840010
Jacksonville, Florida, 32209
Investigational Site Number 840001
Kansas City, Kansas, 66160-7321
Investigational Site Number 840006
Phoenix, Arizona, 85013
Investigational Site Number 840008
St Louis, Missouri, 63110

Other trials in United States

Germany3 sites

Investigational Site Number 276003
Mainz, 55131
Investigational Site Number 276001
München, 80336
Investigational Site Number 276002
Münster, 48149

Other trials in Germany

France2 sites

Investigational Site Number 250003
Nice, 06000
Investigational Site Number 250002
Paris, 75013

Other trials in France

Belgium1 site

Investigational Site Number 056001
Leuven, 3000

Other trials in Belgium

Denmark1 site

Investigational Site Number 208001
København Ø, 2100

Other trials in Denmark

Netherlands1 site

Investigational Site Number 528001
Rotterdam, 3015 GJ

Other trials in Netherlands

United Kingdom1 site

Investigational Site Number 826003
Newcastle upon Tyne, NE1 4LP

Other trials in United Kingdom

About this 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

Primary Objective:

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

Secondary Objective:

Long-term effect of avalglucosidase alfa on pharmacodynamic variables

Read the 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).

Conditions: Glycogen Storage Disease Type II Pompe Disease
Being tested: Avalglucosidase Alfa

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Avalglucosidase AlfaDrug
Also called GZ402666, neoGAA
Pharmaceutical form: lyophilized powder reconstituted for infusion Route of administration: intravenous

Study groups in NCT02032524
Study group	Role	What they receive
Avalglucosidase Alfa	Experimental	administered intravenously every 2 weeks Receives: Drug: Avalglucosidase Alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Infusion Associated Reactions (IARs) and Deaths
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An serious AE (SAE) is any untoward medical occurrence that results: death or life-threatening or inpatient hospitalization or prolongation of existing hospitalization or persistent or significant disability or congenital anomaly or medically important event. TEAEs are defined as AEs that develop or worsen during the on-treatment period (that is, from the time of first dose of IMP up to 4 weeks after the last administration of the IMP). Protocol-defined IARs were defined as AEs that occur during either the infusion or the post-infusion observation period (that is, up to 2 hours or longer following the infusion as per the Investigator's discretion) which were deemed to be related or possibly related to the IMP.
Measured: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Number of Participants With Clinically Significant Physical Examination Abnormalities
Physical examination included, at a minimum, an assessment of the participant's general appearance; skin; head, eyes, ears, nose, and throat; examinations of lymph nodes, abdomen, extremities/joints, neurological and mental status; heart and respiratory auscultation; peripheral arterial pulse; and pupil, knee, achilles, and plantar reflexes.
Measured: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Biochemistry
Blood samples were collected to determine the clinical chemistry laboratory abnormalities.
Measured: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Hematology
Blood samples were collected to determine the hematology laboratory significant abnormalities.
Measured: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Change From Baseline in Urine BUN up to Last IMP Administration
Last on-treatment (LOT) values were collected at or just prior to the last IMP administration.
Measured: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
Change From Baseline in Urine Hyaline Casts up to Last IMP Administration
The LOT values were collected at or just prior to the last IMP administration.
Measured: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
Change From Baseline in Urine Leukocytes [White Blood Cell (WBC)] up to Last IMP Administration
The LOT values were collected at or just prior to the last IMP administration.
Measured: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
Change From Baseline in Urine Specific Gravity up to Last IMP Administration
The LOT values were collected at or just prior to the last IMP administration.
Measured: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
Change From Baseline in Urine pH up to Last IMP Administration
The LOT values were collected at or just prior to the last IMP administration.
Measured: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities
Participants vital signs were examined to determine the abnormalities. Vital signs included heart rate, systolic and diastolic blood pressure.
Measured: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Number of Participants With Body Weight Increased/Decreased
Body weight was measured in kilograms and collected in the electronic case report forms every 3 months throughout the duration of the study, as well as at the end of study visit.
Measured: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Number of Participants With Potentially Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities
Standard 12-lead ECGs were recorded after at least 15 minutes in the supine position using an electrocardiographic device. The following were assessed: heart rate, rhythm, interval between the peaks of successive QRS complexes (RR), interval from the beginning of the P wave until the beginning of the QRS complex (PR), interval from start of the Q wave to the end of the S wave (QRS), interval between the start of the Q wave and the end of the T wave (QT), QT interval corrected for heart rate (QTc) automatic correction evaluation (by the ECG device), QRS axis, R voltage V6, voltage V1, left ventricular hypertrophy criteria, right ventricular hypertrophy criteria, repolarization charges, and overall cardiac impression for each participant.
Measured: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Number of Participants With Antidrug Antibodies (ADA) Status, Positive or Negative
ADA negative was defined as ADAs are not detected (that is, negative in screening assay or reactive in screening but negative in confirmatory assay). ADA positive was defined as ADA was detected (that is, an assay signal equal to or greater than the cut-point in the screening assay and was tested positive in the confirmatory assay).
Measured: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa
Cmax was defined as maximum plasma concentration observed. The non-compartmental pharmacokinetic (PK) analysis was performed.
Measured: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Real Time (AUClast) of Avalglucosidase Alfa
AUClast was calculated using the trapezoidal method from time zero to the real time. The non-compartmental PK analysis was performed.
Measured: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Time Corresponding to the Last Concentration (Tlast) of Avalglucosidase Alfa
Tlast was defined as time corresponding to the last concentration above the limit of quantification, Clast. The non-compartmental PK analysis was performed.
Measured: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Terminal Half-Life (t1/2z) of Avalglucosidase Alfa
t1/2z was calculated according to the following equation: t1/2z = 0.693/λz. Where, λz is the slope of the regression line of the terminal phase of the plasma concentration versus time curve. Half-life was calculated by taking the regression of at least 3 points. The non-compartmental PK analysis was performed.
Measured: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Apparent Total Body Clearance Steady-State (CLss) of Avalglucosidase Alfa
CLss was calculated using the following equation: CLss= dose/AUC. The non-compartmental PK analysis was performed.
Measured: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Apparent Volume of Distribution Steady-State (Vss) of Avalglucosidase Alfa
Vss was calculated using the following equation: Vz= CLss/λz. The non-compartmental PK analysis was performed.
Measured: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312

Secondary outcomes (7)

Change From Baseline in Cross-Sectional Area (CSA) of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). The measured area of each muscle group, CSA was provided.
Measured: Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in Dixon Fat Fraction of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). Three-point dixon imaging provided quantification of fat content in muscles [fat fraction (FF)].
Measured: Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in Index of Real Muscle Mass (IRMM) of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). The FF was combined with the CSA measurements trophicity to provide an IRMM in mm^2 (that is, IRMM = CSA x [1 - FF]). A negative change from baseline value in IRMM of skeletal muscle MRI indicates muscle loss (worse outcome) and a positive change from baseline value indicates muscle gain (better outcome).
Measured: Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in T2 of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). The T2 multi-slice multi-spin echo and B1 mapping provided a quantitative measure of disease activity (edema, inflammation) within muscles.
Measured: Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in T2 With B1 of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). The T2 multi-slice multi-spin echo and B1 mapping provided a quantitative measure of disease activity (edema, inflammation) within muscles.
Measured: Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in Skeletal Muscle Biopsy Up to Week 312
Skeletal muscle needle or open biopsy was performed on the lower extremity (quadriceps) muscle to assess glycogen content. The MRI appearance of the muscle was used to determine the level (axial slice position) that the biopsy procedure should target (avoiding fatty replaced tissue). Glycogen content was measured by histomorphometric analysis or severity grading to determine how effectively avalglucosidase alfa was able to remove glycogen from muscle.
Measured: Baseline (Day 1) and Weeks 27, 104, 208, 260 and 312
Change From Baseline in Urinary Glucose Tetrasaccharide (Hex4) Level Up to Week 442
The Hex4, a tetraglucose oligomer, has been shown to be elevated in the urine of participants with Pompe disease. Hence, determination of Hex4 levels may be a means by which the efficacy of treatments were monitored. Urine samples were collected prior to IMP infusion for the assessment of urinary Hex4 concentrations.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Feb 201412 Dec 2022

First posted10 Jan 2014 (estimated)
Study start27 Feb 2014
Primary completion12 Dec 2022
Study completion12 Dec 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Glycogen Storage Disease Type II Pompe DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02032524
Sponsor's protocol ID: LTS13769
Other IDs: U1111-1147-3439
Acronym: NEO-EXT
Status last verified: Feb 2024
First submitted: 4 Dec 2013
Last updated: 1 Mar 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: 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

Publications

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.
PubMed 35618441

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingObservational study
MENA/Levant Epidemiological, Registry of Immunological & Clinical Traits (MERIT)
Antiphospholipid (aPL)-Positive, Rheumatic Arthritis
Not yet recruitingPhase 2
An Extension Study of S-606001 in Participants With Late-onset Pompe Disease (LOPD)
Pompe Disease
RecruitingPhase 1/2
A Study to Evaluate Safety, Tolerability, and Efficacy of AB-1009 Gene Therapy (GAA Gene) in Adult Participants With Late-Onset Pompe Disease (PROGRESS-GT LOPD)
Pompe Disease (Late-onset), Pompe Disease Late-Onset
Active, not recruiting
A Study About Antibody Levels and Biomarkers in the Blood in People With Late-onset Pompe Disease
Pompe Disease (Late-onset)
RecruitingObservational study
Pompe Disease RWE Long-term Monitoring Program
Pompe Disease

All Glycogen Storage Disease Type II Pompe Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02032524
Acronym / sponsor ID: NEO-EXT / LTS13769
Conditions: Glycogen Storage Disease Type II Pompe Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 19 participants (actual)
Lead sponsor: Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
Study start: 27 Feb 2014 (actual)
Primary completion: 12 Dec 2022 (actual)
Study completion: 12 Dec 2022 (actual)
First posted: 10 Jan 2014 (estimated)
Results: Posted 1 Mar 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Primary Objective:

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

Secondary Objective:

Long-term effect of avalglucosidase alfa on pharmacodynamic variables

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Avalglucosidase Alfa	Experimental	Drug: Avalglucosidase Alfaadministered intravenously every 2 weeks

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Avalglucosidase AlfaAlso: GZ402666, neoGAAPharmaceutical form: lyophilized powder reconstituted for infusion Route of administration: intravenous	Drug	Avalglucosidase Alfa

Primary outcome

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Infusion Associated Reactions (IARs) and Deaths
Time frame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An serious AE (SAE) is any untoward medical occurrence that results: death or life-threatening or inpatient hospitalization or prolongation of existing hospitalization or persistent or significant disability or congenital anomaly or medically important event. TEAEs are defined as AEs that develop or worsen during the on-treatment period (that is, from the time of first dose of IMP up to 4 weeks after the last administration of the IMP). Protocol-defined IARs were defined as AEs that occur during either the infusion or the post-infusion observation period (that is, up to 2 hours or longer following the infusion as per the Investigator's discretion) which were deemed to be related or possibly related to the IMP.
Number of Participants With Clinically Significant Physical Examination Abnormalities
Time frame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Physical examination included, at a minimum, an assessment of the participant's general appearance; skin; head, eyes, ears, nose, and throat; examinations of lymph nodes, abdomen, extremities/joints, neurological and mental status; heart and respiratory auscultation; peripheral arterial pulse; and pupil, knee, achilles, and plantar reflexes.
Number of Participants With Potentially Clinically Significant Abnormalities in Biochemistry
Time frame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Blood samples were collected to determine the clinical chemistry laboratory abnormalities.
Number of Participants With Potentially Clinically Significant Abnormalities in Hematology
Time frame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Blood samples were collected to determine the hematology laboratory significant abnormalities.
Change From Baseline in Urine BUN up to Last IMP Administration
Time frame: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
Last on-treatment (LOT) values were collected at or just prior to the last IMP administration.
Change From Baseline in Urine Hyaline Casts up to Last IMP Administration
Time frame: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
The LOT values were collected at or just prior to the last IMP administration.
Change From Baseline in Urine Leukocytes [White Blood Cell (WBC)] up to Last IMP Administration
Time frame: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
The LOT values were collected at or just prior to the last IMP administration.
Change From Baseline in Urine Specific Gravity up to Last IMP Administration
Time frame: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
The LOT values were collected at or just prior to the last IMP administration.
Change From Baseline in Urine pH up to Last IMP Administration
Time frame: Baseline (Day 1) and last on-treatment values (up to 454 weeks)
The LOT values were collected at or just prior to the last IMP administration.
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities
Time frame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Participants vital signs were examined to determine the abnormalities. Vital signs included heart rate, systolic and diastolic blood pressure.
Number of Participants With Body Weight Increased/Decreased
Time frame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Body weight was measured in kilograms and collected in the electronic case report forms every 3 months throughout the duration of the study, as well as at the end of study visit.
Number of Participants With Potentially Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities
Time frame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Standard 12-lead ECGs were recorded after at least 15 minutes in the supine position using an electrocardiographic device. The following were assessed: heart rate, rhythm, interval between the peaks of successive QRS complexes (RR), interval from the beginning of the P wave until the beginning of the QRS complex (PR), interval from start of the Q wave to the end of the S wave (QRS), interval between the start of the Q wave and the end of the T wave (QT), QT interval corrected for heart rate (QTc) automatic correction evaluation (by the ECG device), QRS axis, R voltage V6, voltage V1, left ventricular hypertrophy criteria, right ventricular hypertrophy criteria, repolarization charges, and overall cardiac impression for each participant.
Number of Participants With Antidrug Antibodies (ADA) Status, Positive or Negative
Time frame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
ADA negative was defined as ADAs are not detected (that is, negative in screening assay or reactive in screening but negative in confirmatory assay). ADA positive was defined as ADA was detected (that is, an assay signal equal to or greater than the cut-point in the screening assay and was tested positive in the confirmatory assay).
Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa
Time frame: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Cmax was defined as maximum plasma concentration observed. The non-compartmental pharmacokinetic (PK) analysis was performed.
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Real Time (AUClast) of Avalglucosidase Alfa
Time frame: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
AUClast was calculated using the trapezoidal method from time zero to the real time. The non-compartmental PK analysis was performed.
Time Corresponding to the Last Concentration (Tlast) of Avalglucosidase Alfa
Time frame: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Tlast was defined as time corresponding to the last concentration above the limit of quantification, Clast. The non-compartmental PK analysis was performed.
Terminal Half-Life (t1/2z) of Avalglucosidase Alfa
Time frame: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
t1/2z was calculated according to the following equation: t1/2z = 0.693/λz. Where, λz is the slope of the regression line of the terminal phase of the plasma concentration versus time curve. Half-life was calculated by taking the regression of at least 3 points. The non-compartmental PK analysis was performed.
Apparent Total Body Clearance Steady-State (CLss) of Avalglucosidase Alfa
Time frame: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
CLss was calculated using the following equation: CLss= dose/AUC. The non-compartmental PK analysis was performed.
Apparent Volume of Distribution Steady-State (Vss) of Avalglucosidase Alfa
Time frame: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Vss was calculated using the following equation: Vz= CLss/λz. The non-compartmental PK analysis was performed.

7 secondary outcomes

Change From Baseline in Cross-Sectional Area (CSA) of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Time frame: Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in Dixon Fat Fraction of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Time frame: Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in Index of Real Muscle Mass (IRMM) of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Time frame: Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in T2 of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Time frame: Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in T2 With B1 of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Time frame: Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in Skeletal Muscle Biopsy Up to Week 312
Time frame: Baseline (Day 1) and Weeks 27, 104, 208, 260 and 312
Change From Baseline in Urinary Glucose Tetrasaccharide (Hex4) Level Up to Week 442
Time frame: 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

Results and safety

Results posted to the registry on 1 Mar 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group 1: Avalglucosidase Alfa 5 mg/kg	4	3
Group 1: Avalglucosidase Alfa 10 mg/kg	3	3
Group 1: Avalglucosidase Alfa 20 mg/kg	3	3
Group 2: Avalglucosidase Alfa 5 mg/kg	4	3
Group 2: Avalglucosidase Alfa 10 mg/kg	4	4
Group 2: Avalglucosidase Alfa 20 mg/kg	6	5

Primary outcome: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Infusion Associated Reactions (IARs) and Deaths

Time frame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks. Count of participants. Unit: Participants

Measure	Group 1: Avalglucosidase Alfa 5 mg/kg n = 4	Group 1: Avalglucosidase Alfa 10 mg/kg n = 3	Group 1: Avalglucosidase Alfa 20 mg/kg n = 3	Group 2: Avalglucosidase Alfa 5 mg/kg n = 4	Group 2: Avalglucosidase Alfa 10 mg/kg n = 4	Group 2: Avalglucosidase Alfa 20 mg/kg n = 6
Any TEAEs	4	3	3	4	4	6
TESAEs	3	1	1	1	1	2
Protocol-defined IARs	2	0	2	2	0	1
Any TEAE leading to death	0	0	0	0	0	0

Population analysed: The safety analysis set included all participants who received at least 1 complete infusion of IMP.

Primary outcome: Number of Participants With Clinically Significant Physical Examination Abnormalities

Time frame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks. Count of participants. Unit: Participants

Measure	Group 2: Avalglucosidase Alfa 10 mg/kg n = 4	Group 2: Avalglucosidase Alfa 20 mg/kg n = 6
Achilles Reflexes	0	1
General Appearance	0	1
Knee Reflexes	0	1
Lymph Nodes	0	1
Neurological Status	2	1

Population analysed: The safety analysis set included all participants who received at least 1 complete infusion of IMP.

Primary outcome: Number of Participants With Potentially Clinically Significant Abnormalities in Biochemistry

Time frame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks. Count of participants. Unit: Participants

Measure	Group 1: Avalglucosidase Alfa 5 mg/kg n = 4	Group 1: Avalglucosidase Alfa 10 mg/kg n = 3	Group 1: Avalglucosidase Alfa 20 mg/kg n = 3	Group 2: Avalglucosidase Alfa 5 mg/kg n = 4	Group 2: Avalglucosidase Alfa 10 mg/kg n = 4	Group 2: Avalglucosidase Alfa 20 mg/kg n = 6
Glucose: <=3.9 millimoles per liter (mmol/L) and < lower limit of normal (LLN)	2	2	2	1	2	1
Glucose: >=11.1 mmol/L (unfasted); >=7 mmol/L (fasted)	2	0	1	1	1	3
Sodium: <=129 mmol/L	0	0	0	1	0	1
Sodium: >=160 mmol/L	0	0	0	0	0	0
Potassium: <3 mmol/L	0	0	0	1	1	0
Potassium: >=5.5 mmol/L	0	0	0	0	0	1
Chloride: <80 mmol/L	0	0	0	0	0	0
Chloride: >115 mmol/L	0	0	0	0	0	0

Population analysed: The safety analysis set included all participants who received at least 1 complete infusion of IMP.

Primary outcome: Number of Participants With Potentially Clinically Significant Abnormalities in Hematology

Time frame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks. Count of participants. Unit: Participants

Measure	Group 1: Avalglucosidase Alfa 5 mg/kg n = 4	Group 1: Avalglucosidase Alfa 10 mg/kg n = 3	Group 1: Avalglucosidase Alfa 20 mg/kg n = 3	Group 2: Avalglucosidase Alfa 5 mg/kg n = 4	Group 2: Avalglucosidase Alfa 10 mg/kg n = 4	Group 2: Avalglucosidase Alfa 20 mg/kg n = 6
Hemoglobin: <=115 g/L (Male); <=95 g/L (Female)	1	0	1	0	0	1
Hemoglobin: >=185 g/L (Male); >=165 g/L (Female)	0	0	0	0	1	0
Hemoglobin: Decrease from baseline >=20 g/L	1	1	1	2	0	1
Hematocrit: <=0.37 volume per volume (v/v) (Male); <=0.32 v/v (Female)	1	0	1	1	1	1
Hematocrit: >=0.55 v/v (Male); >=0.5 v/v (Female)	0	0	0	0	1	0
Platelet Count: <100x10^9/L	0	0	0	0	0	0
Platelet Count: >=700x10^9/L	0	0	0	0	0	0
Erythrocyte Count: >=6x10^12/L	0	0	0	0	1	0

Population analysed: The safety analysis set included all participants who received at least 1 complete infusion of IMP.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: TEAEs data was collected from first dose of IMP up to 4 weeks after the last dose of IMP administration (maximum exposure duration: up to 454 weeks). Death data were collected from first dose of IMP up to the end of the study.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1: Avalglucosidase Alfa 5 mg/kg	3 of 4 (75%)	4 of 4 (100%)	0 of 4
Group 1: Avalglucosidase Alfa 10 mg/kg	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
Group 1: Avalglucosidase Alfa 20 mg/kg	1 of 3 (33.3%)	3 of 3 (100%)	1 of 3
Group 2: Avalglucosidase Alfa 5 mg/kg	1 of 4 (25%)	4 of 4 (100%)	0 of 4
Group 2: Avalglucosidase Alfa 10 mg/kg	1 of 4 (25%)	4 of 4 (100%)	0 of 4
Group 2: Avalglucosidase Alfa 20 mg/kg	2 of 6 (33.3%)	6 of 6 (100%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35618441Dimachkie 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.
Individual participant dataSharing planned: Yes. 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

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Sciences & Operations study director

Sanofi

17 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avalglucosidase Alfa in people with Glycogen Storage Disease Type II Pompe Disease, run by Genzyme, a Sanofi Company at 17 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Germany, France, Belgium, Denmark and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Infusion Associated Reactions (IARs) and Deaths (time frame: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks). The study lists 19 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02032524, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2024.