Pompe DiseasePhase 4PAPAYANCT01410890
Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease
A Phase 4 study testing alglucosidase alfa in people with Pompe Disease and Glycogen Storage Disease Type II (GSD II), run by Genzyme, a Sanofi Company at 12 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Pompe Disease, Glycogen Storage Disease Type II (GSD II)
- What is being tested?
- alglucosidase alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 12 sitesin 6 countries
- Study dates
- 3 Nov 2014to 20 Nov 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
12 sites in 6 countries.
12 sites in 6 countries
United States4 sites
Investigational Site Number 840007
Cincinnati, Ohio, 45219
Investigational Site Number 840003
Fairfax, Virginia, 22030
Investigational Site Number 840005
Salt Lake City, Utah, 84108
Investigational Site Number 840008
Valhalla, New York, 10595
India2 sites
Investigational Site Number 356001
New Delhi, 110 029
Investigational Site Number 356002
Vellore, 632004
Russia2 sites
Investigational Site Number 643001
Moscow, 125367
Investigational Site Number 643002
Moscow, 125412
United Kingdom2 sites
Investigational Site Number 826003
Birmingham, B4 6NH
Investigational Site Number 826002
Salford, M6 8HD
About this study
Official title: 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.
Read the 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.
- Being tested
- alglucosidase alfa
- Medical subject headings
- Glycogen Storage Disease Type II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
alglucosidase alfaBiological
Also called Lumizyme
Intravenous (IV) infusion of 20mg/kg body weight every other week (qow)
| Study group | Role | What they receive |
|---|---|---|
| Alglucosidase alfa | Experimental | 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. Receives: Biological: alglucosidase alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Alglucosidase Alfa
Cmax was defined as maximum observed plasma concentration.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2011 (estimated)
- Study start3 Nov 2014
- Primary completion20 Nov 2020
- Study completion20 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pompe DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01410890
- Sponsor's protocol ID
- AGLU07710
- Other IDs
- 2010-022231-11, MSC12790
- Acronym
- PAPAYA
- Status last verified
- Mar 2022
- First submitted
- 2 Aug 2011
- Last updated
- 28 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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
Publications
Nicolas X, Hurbin F, Periquet M, Richards S, Sensinger C, Welch K, An Haack K. Pharmacokinetics of Alglucosidase Alfa Manufactured at the 4000-L Scale in Participants with Pompe Disease: A Phase 3/4 Open-Label Study. Clin Pharmacol Drug Dev. 2023 Dec;12(12):1185-1193. doi: 10.1002/cpdd.1314. Epub 2023 Sep 13.
PubMed 37705424
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3/4 Prospective Study to Characterize the Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease
- ClinicalTrials.gov ID
- NCT01410890
- Acronym / sponsor ID
- PAPAYA / AGLU07710
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- 3 Nov 2014 (actual)
- Primary completion
- 20 Nov 2020 (actual)
- Study completion
- 20 Nov 2020 (actual)
- First posted
- 5 Aug 2011 (estimated)
- Results
- Posted 11 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alglucosidase alfa | Experimental | Biological: alglucosidase alfaParticipants 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| alglucosidase alfaAlso: LumizymeIntravenous (IV) infusion of 20mg/kg body weight every other week (qow) | Biological | Alglucosidase alfa |
Primary outcome
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.
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.
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.
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.
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.
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.
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.
7 secondary outcomes
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
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
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
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37705424Nicolas X, Hurbin F, Periquet M, Richards S, Sensinger C, Welch K, An Haack K. Pharmacokinetics of Alglucosidase Alfa Manufactured at the 4000-L Scale in Participants with Pompe Disease: A Phase 3/4 Open-Label Study. Clin Pharmacol Drug Dev. 2023 Dec;12(12):1185-1193. doi: 10.1002/cpdd.1314. Epub 2023 Sep 13.
- Individual participant dataSharing planned: Yes. 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
Related trials for Pompe Disease
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
Recruiting
Transcriptomic Analysis to Put an End to Misdiagnosis in Patients With Rare Muscle Diseases
Rare Genetic Muscle Diseases, Muscular Dystrophy, Duchenne
RecruitingObservational study
Pompe Disease Registry Protocol
Glycogen Storage Disease Type II, Pompe Disease
Not yet recruitingObservational study
MENA/Levant Epidemiological, Registry of Immunological & Clinical Traits (MERIT)
Antiphospholipid (aPL)-Positive, Rheumatic Arthritis
Not yet recruitingPhase 2
An Extension Study of S-606001 in Participants With Late-onset Pompe Disease (LOPD)
Pompe Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Genzyme, a Sanofi Company
12 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing alglucosidase alfa in people with Pompe Disease and Glycogen Storage Disease Type II (GSD II), run by Genzyme, a Sanofi Company at 12 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, India, Russia, United Kingdom, Bulgaria and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01410890, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2022.