Avalglucosidase Alfa Extension Study

NCT02032524 | Completed Phase 2 Results DMC

• 2 other identifiers: LTS13769U1111-1147-3439
• Study Type: interventional
• Target: 19
• Locations: 7 countries
• Sites: 17

Brief Summary

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

Conditions

Glycogen Storage Disease Type II Pompe Disease

Outcome Measures

Primary Outcomes (19)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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).

  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.

  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.

  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.

  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.

  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.

  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.

  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

  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

  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

  Baseline (Day 1) and Weeks 104 and 442

• Change From Baseline in T2 of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442

  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

  Baseline (Day 1) and Weeks 104 and 442

Study Arms (1)

Avalglucosidase Alfa

EXPERIMENTAL

administered intravenously every 2 weeks

Drug: Avalglucosidase Alfa

Interventions

Avalglucosidase Alfa DRUG

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

Also known as: GZ402666, neoGAA

Avalglucosidase Alfa

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (17)

Investigational Site Number 840006

Phoenix, Arizona, 85013, United States

Location

Investigational Site Number 840010

Jacksonville, Florida, 32209, United States

Location

Investigational Site Number 840001

Kansas City, Kansas, 66160-7321, United States

Location

Investigational Site Number 840008

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 840002

Durham, North Carolina, 27710, United States

Location

Investigational Site Number 840011

Cincinnati, Ohio, 45219, United States

Location

Investigational Site Number 840009

Dallas, Texas, 75390, United States

Location

Investigational Site Number 840003

Fairfax, Virginia, 22030, United States

Location

Investigational Site Number 056001

Leuven, 3000, Belgium

Location

Investigational Site Number 208001

København Ø, 2100, Denmark

Location

Investigational Site Number 250003

Nice, 06000, France

Location

Investigational Site Number 250002

Paris, 75013, France

Location

Investigational Site Number 276003

Mainz, 55131, Germany

Location

Investigational Site Number 276001

München, 80336, Germany

Location

Investigational Site Number 276002

Münster, 48149, Germany

Location

Investigational Site Number 528001

Rotterdam, 3015 GJ, Netherlands

Location

Investigational Site Number 826003

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35618441 DERIVED

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi-Aventis Recherche & Developpement

contact-us@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2013
• First Posted: January 10, 2014
• Study Start: February 27, 2014
• Primary Completion: December 12, 2022
• Study Completion: December 12, 2022
• Last Updated: March 1, 2024
• Results First Posted: March 1, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share

Locations

DE (3); NL (1); US (8); BE (1); DK (1); GB (1); FR (2)