Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease (PAPAYA)

A Phase 3/4 Prospective Study to Characterize the Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease

• The primary objective of this study was to characterize the pharmacokinetics (PK) of alglucosidase alfa manufactured at the 4000 L scale in participants who had a confirmed diagnosis of Pompe disease.
• A secondary objective of this study was to evaluate and explore the relationship between anti-recombinant human acid alpha-glucosidase antibody titers and the PK of alglucosidase alfa.

Study Overview

• Status: Completed
• Conditions: Pompe Disease; Glycogen Storage Disease Type II (GSD II)
• Intervention / Treatment: Biological: alglucosidase alfa

Detailed Description

The total study duration per participant was 4 to 8 weeks that consisted of a screening period (from 2 days to 4 weeks), treatment visit (1 day), and a follow up call (greater than or equal to 30 days). Two participants enrolled prior to protocol amendment 2 (dated 17 December 2015), which changed the study to single-dose, and were treated for 26 weeks, with a 4-week follow up.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1113
    • Investigational Site Number 1028
• India
  • New Delhi, India, 110 029
    • Investigational Site Number 356001
  • Vellore, India, 632004
    • Investigational Site Number 356002
• Russian Federation
  • Moscow, Russian Federation, 125367
    • Investigational Site Number 643001
  • Moscow, Russian Federation, 125412
    • Investigational Site Number 643002
• Ukraine
  • Kiev, Ukraine, 01135
    • Investigational Site Number 804001
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Investigational Site Number 826003
  • Salford, United Kingdom, M6 8HD
    • Investigational Site Number 826002
• United States
  • New York
    • Valhalla, New York, United States, 10595
      • Investigational Site Number 840008
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Investigational Site Number 840007
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Investigational Site Number 840005
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Investigational Site Number 840003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

A participant was to meet all of the following criteria to be eligible for this study:

• The participant and/or the participant's parent/legal guardian was willing and able to provide signed informed consent.
• The participant had a confirmed acid alpha-glucosidase (GAA) enzyme deficiency from skin, blood, or muscle tissue and/or 2 confirmed GAA gene mutations.
• Infant and toddler Pompe disease participants could be included in the study only under condition (minimal body weight) that the trial-related blood loss (including any losses in the maneuver) would not exceed 3 percent (%) of the total blood volume during a period of 4 weeks and would not exceed 1 % at any single time.
• The participant, if female and of childbearing potential, must have had a negative pregnancy test (urine beta-human chorionic gonadotropin) at screening. Note: All female participants of childbearing potential and sexually mature males must have agreed to use a medically accepted method of contraception throughout the study.
• For participants previously treated with alglucosidase alfa the participant had received alglucosidase alfa for at least 6 months.

Exclusion Criteria:

A participant who met any of the following criteria was excluded from this study:

• The participant was participating in another clinical study using an investigational product.
• The participant, in the opinion of the Investigator, was unable to adhere to the requirements of the study.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Alglucosidase alfa; Participants received intravenous (IV) infusion of Alglucosidase alfa 20 milligrams per kilogram (mg/kg) body weight on Day 1. Infusion was administered at an initial rate of approximately 1 milligram per kilogram per hour (mg/kg/hr) with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of infusion-associated reactions (IARs), until a maximum rate of approximately 7 mg/kg/hr was reached.

Biological: alglucosidase alfa; Intravenous (IV) infusion of 20mg/kg body weight every other week (qow); Other Names: Lumizyme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Alglucosidase Alfa	Cmax was defined as maximum observed plasma concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alglucosidase Alfa	Tmax was defined as time to reach maximum observed plasma concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve (AUC) of Alglucosidase Alfa	AUC was defined as area under the plasma concentration-time curve from time 0 to 24 hours post-dose.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Alglucosidase Alfa	AUC0-last was defined as area under the concentration-time curve from time 0 to the time of the last quantifiable concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Pharmacokinetics: Terminal Elimination Half-life (T1/2) of Alglucosidase Alfa	T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Pharmacokinetics: Total Systemic Clearance (CL) of Alglucosidase Alfa	CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Pharmacokinetics: Volume of Distribution at Steady State (Vss) of Alglucosidase Alfa	Volume of distribution (Vd) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is the apparent volume of distribution at steady-state.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Maximum Observed Plasma Concentration of Alglucosidase Alfa in Anti-Recombinant Human Acid Alpha-Glucosidase Antibody Positive and Negative Participants	Cmax was defined as maximum observed plasma concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration in Anti-rhGAA Antibody Positive and Negative Participants	Tmax was defined as time to reach maximum observed plasma concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Pharmacokinetics: Terminal Elimination Half-life of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants	T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants	AUC0-last was defined as area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 and Extrapolated to Infinite Time (AUC0-inf) in Anti-rhGAA Antibody Positive and Negative Participants	AUC0-inf was defined as area under the concentration-time curve from time 0 extrapolated to infinite time.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Pharmacokinetics: Total Systemic Clearance in Anti-rhGAA Antibody Positive and Negative Participants	CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Pharmacokinetics: Volume of Distribution in Anti-rhGAA Antibody Positive and Negative Participants	Vd is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is the apparent volume of distribution at steady-state.	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 3, 2014
• Primary Completion (ACTUAL): November 20, 2020
• Study Completion (ACTUAL): November 20, 2020

Study Registration Dates

• First Submitted: August 2, 2011
• First Submitted That Met QC Criteria: August 4, 2011
• First Posted (ESTIMATE): August 5, 2011

Study Record Updates

• Last Update Posted (ACTUAL): March 28, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease Type II; Glycogen Storage Disease
• Other Study ID Numbers: AGLU07710; 2010-022231-11 (EUDRACT_NUMBER); MSC12790 (OTHER: Sanofi)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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