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

• ClinicalTrials.gov Identifier: NCT01410890
• Recruitment Status: Completed
• First Posted: August 5, 2011
• Results First Posted: June 11, 2021
• Last Update Posted: March 28, 2022
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Study Description

Brief Summary:

• 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.

Condition or disease	Intervention/treatment	Phase
Pompe Disease; Glycogen Storage Disease Type II (GSD II)	Biological: alglucosidase alfa	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 3/4 Prospective Study to Characterize the Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease
• Actual Study Start Date: November 3, 2014
• Actual Primary Completion Date: November 20, 2020
• Actual Study Completion Date: November 20, 2020

Arms and Interventions

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 Name: Lumizyme

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Alglucosidase Alfa [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   Cmax was defined as maximum observed plasma concentration.
2. Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alglucosidase Alfa [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   Tmax was defined as time to reach maximum observed plasma concentration.
3. Pharmacokinetics: Area Under the Plasma Concentration-Time Curve (AUC) of Alglucosidase Alfa [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   AUC was defined as area under the plasma concentration-time curve from time 0 to 24 hours post-dose.
4. Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Alglucosidase Alfa [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   AUC0-last was defined as area under the concentration-time curve from time 0 to the time of the last quantifiable concentration.
5. Pharmacokinetics: Terminal Elimination Half-life (T1/2) of Alglucosidase Alfa [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.
6. Pharmacokinetics: Total Systemic Clearance (CL) of Alglucosidase Alfa [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
7. Pharmacokinetics: Volume of Distribution at Steady State (Vss) of Alglucosidase Alfa [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   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.

Secondary Outcome Measures :

1. Pharmacokinetics: Maximum Observed Plasma Concentration of Alglucosidase Alfa in Anti-Recombinant Human Acid Alpha-Glucosidase Antibody Positive and Negative Participants [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   Cmax was defined as maximum observed plasma concentration.
2. Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration in Anti-rhGAA Antibody Positive and Negative Participants [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   Tmax was defined as time to reach maximum observed plasma concentration.
3. Pharmacokinetics: Terminal Elimination Half-life of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.
4. 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 [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   AUC0-last was defined as area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration.
5. 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 [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   AUC0-inf was defined as area under the concentration-time curve from time 0 extrapolated to infinite time.
6. Pharmacokinetics: Total Systemic Clearance in Anti-rhGAA Antibody Positive and Negative Participants [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
7. Pharmacokinetics: Volume of Distribution in Anti-rhGAA Antibody Positive and Negative Participants [ Time Frame: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, New York

Investigational Site Number 840008

Valhalla, New York, United States, 10595

United States, Ohio

Investigational Site Number 840007

Cincinnati, Ohio, United States, 45219

United States, Utah

Investigational Site Number 840005

Salt Lake City, Utah, United States, 84108

United States, Virginia

Investigational Site Number 840003

Fairfax, Virginia, United States, 22030

Bulgaria

Investigational Site Number 1028

Sofia, Bulgaria, 1113

India

Investigational Site Number 356001

New Delhi, India, 110 029

Investigational Site Number 356002

Vellore, India, 632004

Russian Federation

Investigational Site Number 643001

Moscow, Russian Federation, 125367

Investigational Site Number 643002

Moscow, Russian Federation, 125412

Ukraine

Investigational Site Number 804001

Kiev, Ukraine, 01135

United Kingdom

Investigational Site Number 826003

Birmingham, United Kingdom, B4 6NH

Investigational Site Number 826002

Salford, United Kingdom, M6 8HD

Sponsors and Collaborators

Genzyme, a Sanofi Company

Investigators

• Study Director: Medical Monitor; Genzyme, a Sanofi Company

  Study Documents (Full-Text)

Documents provided by Sanofi ( Genzyme, a Sanofi Company ):

Study Protocol  [PDF] July 18, 2016

Statistical Analysis Plan  [PDF] December 23, 2016

More Information

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01410890
• Other Study ID Numbers: AGLU07710; 2010-022231-11 ( EudraCT Number ); MSC12790 ( Other Identifier: Sanofi )
• First Posted: August 5, 2011
• Results First Posted: June 11, 2021
• Last Update Posted: March 28, 2022
• Last Verified: March 2022

Individual Participant Data (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

Additional relevant MeSH terms:

Glycogen Storage Disease Type II; Glycogen Storage Disease; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases