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Trial record 1 of 1 for:    NCT01410890
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Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease (PAPAYA)

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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:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

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.

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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


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




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.



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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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01410890


Locations
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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
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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

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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    Key Record Dates
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:
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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