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

Primary Purpose

Pompe Disease, Glycogen Storage Disease Type II (GSD II)

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
alglucosidase alfa
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Pompe Disease

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number 840008
  • Investigational Site Number 840007
  • Investigational Site Number 840005
  • Investigational Site Number 840003
  • Investigational Site Number 1028
  • Investigational Site Number 356001
  • Investigational Site Number 356002
  • Investigational Site Number 643001
  • Investigational Site Number 643002
  • Investigational Site Number 804001
  • Investigational Site Number 826003
  • Investigational Site Number 826002

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Alglucosidase alfa

Arm Description

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.

Outcomes

Primary Outcome Measures

Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Alglucosidase Alfa
Cmax was defined as maximum observed plasma concentration.
Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alglucosidase Alfa
Tmax was defined as time to reach maximum observed plasma concentration.
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.
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.
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.
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.
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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
August 2, 2011
Last Updated
March 15, 2022
Sponsor
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT01410890
Brief Title
Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease
Acronym
PAPAYA
Official Title
A Phase 3/4 Prospective Study to Characterize the Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
November 3, 2014 (Actual)
Primary Completion Date
November 20, 2020 (Actual)
Study Completion Date
November 20, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pompe Disease, Glycogen Storage Disease Type II (GSD II)

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alglucosidase alfa
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
alglucosidase alfa
Other Intervention Name(s)
Lumizyme
Intervention Description
Intravenous (IV) infusion of 20mg/kg body weight every other week (qow)
Primary Outcome Measure Information:
Title
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Alglucosidase Alfa
Description
Cmax was defined as maximum observed plasma concentration.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Title
Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alglucosidase Alfa
Description
Tmax was defined as time to reach maximum observed plasma concentration.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Title
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve (AUC) of Alglucosidase Alfa
Description
AUC was defined as area under the plasma concentration-time curve from time 0 to 24 hours post-dose.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Title
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Alglucosidase Alfa
Description
AUC0-last was defined as area under the concentration-time curve from time 0 to the time of the last quantifiable concentration.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Title
Pharmacokinetics: Terminal Elimination Half-life (T1/2) of Alglucosidase Alfa
Description
T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Title
Pharmacokinetics: Total Systemic Clearance (CL) of Alglucosidase Alfa
Description
CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Title
Pharmacokinetics: Volume of Distribution at Steady State (Vss) of Alglucosidase Alfa
Description
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.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Secondary Outcome Measure Information:
Title
Pharmacokinetics: Maximum Observed Plasma Concentration of Alglucosidase Alfa in Anti-Recombinant Human Acid Alpha-Glucosidase Antibody Positive and Negative Participants
Description
Cmax was defined as maximum observed plasma concentration.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Title
Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration in Anti-rhGAA Antibody Positive and Negative Participants
Description
Tmax was defined as time to reach maximum observed plasma concentration.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Title
Pharmacokinetics: Terminal Elimination Half-life of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants
Description
T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Title
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
Description
AUC0-last was defined as area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Title
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
Description
AUC0-inf was defined as area under the concentration-time curve from time 0 extrapolated to infinite time.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Title
Pharmacokinetics: Total Systemic Clearance in Anti-rhGAA Antibody Positive and Negative Participants
Description
CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Title
Pharmacokinetics: Volume of Distribution in Anti-rhGAA Antibody Positive and Negative Participants
Description
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.
Time Frame
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Genzyme, a Sanofi Company
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 840008
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Investigational Site Number 840007
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Investigational Site Number 840005
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States
Facility Name
Investigational Site Number 840003
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22030
Country
United States
Facility Name
Investigational Site Number 1028
City
Sofia
ZIP/Postal Code
1113
Country
Bulgaria
Facility Name
Investigational Site Number 356001
City
New Delhi
ZIP/Postal Code
110 029
Country
India
Facility Name
Investigational Site Number 356002
City
Vellore
ZIP/Postal Code
632004
Country
India
Facility Name
Investigational Site Number 643001
City
Moscow
ZIP/Postal Code
125367
Country
Russian Federation
Facility Name
Investigational Site Number 643002
City
Moscow
ZIP/Postal Code
125412
Country
Russian Federation
Facility Name
Investigational Site Number 804001
City
Kiev
ZIP/Postal Code
01135
Country
Ukraine
Facility Name
Investigational Site Number 826003
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Facility Name
Investigational Site Number 826002
City
Salford
ZIP/Postal Code
M6 8HD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease

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