Pompe DiseasePhase 4NCT00701701
Immune Tolerance Induction Study
A Phase 4 study testing Myozyme® (alglucosidase alfa) in people with Pompe Disease and Glycogen Storage Disease Type II (GSD-II), run by Genzyme, a Sanofi Company at 5 sites in 2 countries.
Trial summary
An exploratory, open-labeled study of participants with Pompe disease, who had previously received Myozyme® (alglucosidase alfa) treatment, to evaluate the efficacy, safety and clinical benefit of 2 Immune Tolerance Induction (ITI) regimens in combination with Myozyme®. Read more about this study
- Who is it for?
- Ages 1 month and older
- Conditions the study is for
- Pompe Disease, Glycogen Storage Disease Type II (GSD-II), Glycogenesis 2 Acid Maltase Deficiency
- What is being tested?
- Myozyme® (alglucosidase alfa)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 14 Dec 2008to 18 Feb 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 1 month and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The participant (and/or participant's legal guardian if participant was < 18 years) provided written informed consent prior to any study-related procedures that were performed.
- The participants had a confirmed diagnosis of Pompe disease defined as a documented acid α-glucosidase (GAA) enzyme deficiency from any tissue source or 2 GAA gene mutations.
- The participant (and/or legal guardian) had ability to comply with clinical protocol.
- If the participant was CRIM-positive, he/she had received at least 6 consecutive months of Myozyme® infusions (20 mg/kg qow).
- If the participant was CRIM-negative, he/she had received at least 1 Myozyme® infusion prior to enrollment.
- Regimen A only: The participants exhibits clinical decline; The participant had persistent high anti-recombinant human acid α-glucosidase (anti-rhGAA) antibody titers and/or tested positive for antibodies that inhibit enzymatic activity and/or uptake of Myozyme®;
- Regimen B only: The participant was CRIM-negative AND The participant did not exhibit clinical decline; OR all of the following: The participant was CRIM-negative AND The participant exhibited clinical decline AND The participant did not exhibit high anti-rhGAA antibody titers and had not tested positive for antibodies that inhibit enzymatic activity and/or uptake of Myozyme®.
Who cannot join
- The participant had a clinical condition unrelated to Pompe disease that would interfere with program assessments.
- The participant was at risk of reactivation or was a carrier of Hepatitis B or Hepatitis C.
- The participant was at risk of reactivation or had positive serology suggestive of active infection for cytomegalovirus, Herpes simplex, JC virus, Parvovirus or Epstein Barr virus.
- The participant was at risk of reactivation of tuberculosis or had regular contact with individuals who were being actively treated for tuberculosis.
- The participant had low serum albumin.
- The participant had a major congenital abnormality.
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- The participant had used any investigational product (other than alglucosidase alfa) within 30 days prior to study enrollment.
- The participant was pregnant or lactating.
- The participant has had or was required to have any live vaccination within one month prior to enrollment.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Study site
Durham, North Carolina
Study site
Louisville, Kentucky
Study site
Norfolk, Virginia
Study site
Salt Lake City, Utah
About this study
Official title: An Exploratory Study of the Safety and Efficacy of Immune Tolerance Induction (ITI) in Patients With Pompe Disease Who Have Previously Received Myozyme
An exploratory, open-labeled study of participants with Pompe disease, who had previously received Myozyme® (alglucosidase alfa) treatment, to evaluate the efficacy, safety and clinical benefit of 2 Immune Tolerance Induction (ITI) regimens in combination with Myozyme®. Eligible participants who were then receiving Myozyme® therapy were enrolled into the study, and were followed for a minimum of 18 months on-study (a 6-month ITI treatment module and a 12-month follow-up module on Myozyme® alone). Eligible participants were followed for a minimum of 18 months on treatment or, if a participant was <6 months of age at the time of enrollment, until the participant was 2 years of age. Both cross-reacting immunologic material (CRIM)-negative and CRIM-positive participants were eligible for Regimen A depending if they met the required criteria. Regimen B, however, was limited to CRIM-negative participants.
- Conditions
- Pompe Disease, Glycogen Storage Disease Type II (GSD-II), Glycogenesis 2 Acid Maltase Deficiency
- Being tested
- Myozyme® (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.
Myozyme® (alglucosidase alfa)Biological
Also called Myozyme®
Myozyme®: IV infusion of 20 mg/kg qow; Cyclophosphamide: 250 mg/m^2 IV q4w after Myozyme infusion for 6 months.
Myozyme® (alglucosidase alfa)Biological
Also called Myozyme®
Myozyme®: IV infusion of 20 mg/kg qow; Rituximab: 375 mg/m^2 IV weekly beginning the day after Myozyme infusion for 4 weeks (an optional additional 2nd cycle could be administered at the discretion of the investigator); Methotrexate: 15 mg/m^2 subcutaneous qow on the day after Myozyme infusion for 6 months.
| Study group | Role | What they receive |
|---|---|---|
| Regimen A: Alglucosidase alfa and Cyclophosphamide | Experimental | Participants exhibiting clinical decline since starting alglucosidase alfa (Myozyme®) therapy and having inhibitory antibodies and/or a sustained high recombinant human acid alpha-glucosidase (rhGAA) antibody titer (defined as at least 2 titers greater than or equal to [>=] 25,600 obtained at least 1 month apart), regardless of their CRIM status, were assigned to Regimen A. In Regimen A, participants received alglucosidase alfa (Myozyme®) Intravenous (IV) infusion of 20 milligram per kilogram (mg/kg) every other week (qow) for a minimum of 18 months or, until the participant reached the age of 2 years (if the participant was less than [<6] months of age at the time of enrollment). In addition, cyclophosphamide 250 milligram per square meter (mg/m^2) IV infusion was administered every 4 weeks (q4w) after Myozyme® infusion for 6 months. Receives: Biological: Myozyme® (alglucosidase alfa) |
| Regimen B: Alglucosidase alfa, Rituximab and Methotrexate | Experimental | CRIM-negative participants were assigned to Regimen B if they either(1)exhibited clinical decline since starting alglucosidase alfa (Myozyme®)therapy and did not have inhibitory antibodies and/or a sustained rhGAA antibody titer(defined as at least 2 titers >=25,600 obtained at least 1 month apart),or(2) did not exhibit clinical decline since starting alglucosidase alfa(Myozyme®) therapy, regardless of their anti-rhGAA or inhibitory antibody status. Regimen B participants with CRIM-negative status received alglucosidase alfa(Myozyme®) IV infusion of 20 mg/kg qow for a minimum of 18 months or,until participant reached the age of 2 years (if participant was <6 months of age at time of enrollment). In addition,rituximab 375 mg/m^2 IV was administered weekly beginning the day after Myozyme® infusion for 4 weeks(an optional 2nd cycle could be administered at the discretion of the investigator) and biweekly methotrexate 15 mg/m^2 subcutaneous on the day after Myozyme® infusion for 6 months. Receives: Biological: Myozyme® (alglucosidase alfa) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An Adverse event (AE) was defined as any undesirable physical, psychological, or behavioral effect experienced by participant during his/her participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not product-related. TEAEs were defined as AEs that occurred or worsened during the on-treatment period (time from the start of investigational medicinal product [IMP] administration up to 18 months). Serious AE (SAE) was any AE that resulted in any of the following outcomes: death, was life-threatening, required or prolonged inpatient hospitalization, persistent or significant disability/incapacity; congenital anomaly; or important medical events that may jeopardize the patient or participant and may require medical or surgical intervention to prevent one of the outcomes listed above; and/or new invasive ventilator use.
Measured: From Baseline up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2008 (estimated)
- Study start14 Dec 2008
- Primary completion18 Feb 2020
- Study completion18 Feb 2020
Why it stopped: Study was conducted to fulfill a post marketing commitment (PMC 6). FDA acknowledged fulfillment of PMC.
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.
- 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4 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
- NCT00701701
- Sponsor's protocol ID
- MSC12817
- Other IDs
- AGLU03707, 2015-000583-34, 2015
- Status last verified
- Mar 2022
- First submitted
- 17 Jun 2008
- Last updated
- 7 Apr 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
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Study of the Safety and Efficacy of Immune Tolerance Induction (ITI) in Patients With Pompe Disease Who Have Previously Received Myozyme
- ClinicalTrials.gov ID
- NCT00701701
- Acronym / sponsor ID
- MSC12817
- Conditions
- Pompe Disease, Glycogen Storage Disease Type II (GSD-II), Glycogenesis 2 Acid Maltase Deficiency
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was conducted to fulfill a post marketing commitment (PMC 6). FDA acknowledged fulfillment of PMC.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- 14 Dec 2008 (actual)
- Primary completion
- 18 Feb 2020 (actual)
- Study completion
- 18 Feb 2020 (actual)
- First posted
- 19 Jun 2008 (estimated)
- Results
- Posted 12 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An exploratory, open-labeled study of participants with Pompe disease, who had previously received Myozyme® (alglucosidase alfa) treatment, to evaluate the efficacy, safety and clinical benefit of 2 Immune Tolerance Induction (ITI) regimens in combination with Myozyme®. Eligible participants who were then receiving Myozyme® therapy were enrolled into the study, and were followed for a minimum of 18 months on-study (a 6-month ITI treatment module and a 12-month follow-up module on Myozyme® alone). Eligible participants were followed for a minimum of 18 months on treatment or, if a participant was <6 months of age at the time of enrollment, until the participant was 2 years of age. Both cross-reacting immunologic material (CRIM)-negative and CRIM-positive participants were eligible for Regimen A depending if they met the required criteria. Regimen B, however, was limited to CRIM-negative participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Regimen A: Alglucosidase alfa and Cyclophosphamide | Experimental | Biological: Myozyme® (alglucosidase alfa)Participants exhibiting clinical decline since starting alglucosidase alfa (Myozyme®) therapy and having inhibitory antibodies and/or a sustained high recombinant human acid alpha-glucosidase (rhGAA) antibody titer (defined as at least 2 titers greater than or equal to [>=] 25,600 obtained at least 1 month apart), regardless of their CRIM status, were assigned to Regimen A. In Regimen A, participants received alglucosidase alfa (Myozyme®) Intravenous (IV) infusion of 20 milligram per kilogram (mg/kg) every other week (qow) for a minimum of 18 months or, until the participant reached the age of 2 years (if the participant was less than [<6] months of age at the time of enrollment). In addition, cyclophosphamide 250 milligram per square meter (mg/m^2) IV infusion was administered every 4 weeks (q4w) after Myozyme® infusion for 6 months. |
| Regimen B: Alglucosidase alfa, Rituximab and Methotrexate | Experimental | Biological: Myozyme® (alglucosidase alfa)CRIM-negative participants were assigned to Regimen B if they either(1)exhibited clinical decline since starting alglucosidase alfa (Myozyme®)therapy and did not have inhibitory antibodies and/or a sustained rhGAA antibody titer(defined as at least 2 titers >=25,600 obtained at least 1 month apart),or(2) did not exhibit clinical decline since starting alglucosidase alfa(Myozyme®) therapy, regardless of their anti-rhGAA or inhibitory antibody status. Regimen B participants with CRIM-negative status received alglucosidase alfa(Myozyme®) IV infusion of 20 mg/kg qow for a minimum of 18 months or,until participant reached the age of 2 years (if participant was <6 months of age at time of enrollment). In addition,rituximab 375 mg/m^2 IV was administered weekly beginning the day after Myozyme® infusion for 4 weeks(an optional 2nd cycle could be administered at the discretion of the investigator) and biweekly methotrexate 15 mg/m^2 subcutaneous on the day after Myozyme® infusion for 6 months. |
Who may qualify
- Ages
- 1 month and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- The participant (and/or participant's legal guardian if participant was < 18 years) provided written informed consent prior to any study-related procedures that were performed.
- The participants had a confirmed diagnosis of Pompe disease defined as a documented acid α-glucosidase (GAA) enzyme deficiency from any tissue source or 2 GAA gene mutations.
- The participant (and/or legal guardian) had ability to comply with clinical protocol.
- If the participant was CRIM-positive, he/she had received at least 6 consecutive months of Myozyme® infusions (20 mg/kg qow).
- If the participant was CRIM-negative, he/she had received at least 1 Myozyme® infusion prior to enrollment.
Key exclusion criteria (9 listed)
- The participant had a clinical condition unrelated to Pompe disease that would interfere with program assessments.
- The participant was at risk of reactivation or was a carrier of Hepatitis B or Hepatitis C.
- The participant was at risk of reactivation or had positive serology suggestive of active infection for cytomegalovirus, Herpes simplex, JC virus, Parvovirus or Epstein Barr virus.
- The participant was at risk of reactivation of tuberculosis or had regular contact with individuals who were being actively treated for tuberculosis.
- The participant had low serum albumin.
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 |
|---|---|---|
| Myozyme® (alglucosidase alfa)Also: Myozyme®Myozyme®: IV infusion of 20 mg/kg qow; Cyclophosphamide: 250 mg/m^2 IV q4w after Myozyme infusion for 6 months. | Biological | Regimen A: Alglucosidase alfa and Cyclophosphamide |
| Myozyme® (alglucosidase alfa)Also: Myozyme®Myozyme®: IV infusion of 20 mg/kg qow; Rituximab: 375 mg/m^2 IV weekly beginning the day after Myozyme infusion for 4 weeks (an optional additional 2nd cycle could be administered at the discretion of the investigator); Methotrexate: 15 mg/m^2 subcutaneous qow on the day after Myozyme infusion for 6 months. | Biological | Regimen B: Alglucosidase alfa, Rituximab and Methotrexate |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From Baseline up to 18 months
An Adverse event (AE) was defined as any undesirable physical, psychological, or behavioral effect experienced by participant during his/her participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not product-related. TEAEs were defined as AEs that occurred or worsened during the on-treatment period (time from the start of investigational medicinal product [IMP] administration up to 18 months). Serious AE (SAE) was any AE that resulted in any of the following outcomes: death, was life-threatening, required or prolonged inpatient hospitalization, persistent or significant disability/incapacity; congenital anomaly; or important medical events that may jeopardize the patient or participant and may require medical or surgical intervention to prevent one of the outcomes listed above; and/or new invasive ventilator use.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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
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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
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Myozyme® (alglucosidase alfa) in people with Pompe Disease and Glycogen Storage Disease Type II (GSD-II), run by Genzyme, a Sanofi Company at 5 sites in 2 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 7 inclusion and 9 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: stopped early, as of the sponsor's last update on 7 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Israel. 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 12 Oct 2020). 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?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: From Baseline up to 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Apr 2022.