Clinical trial NCT00701701: Immune Tolerance Induction 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Pompe Disease
Glycogen Storage Disease Type II (GSD-II)
Glycogenesis 2 Acid Maltase Deficiency
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2008-06-19
Enrollment: 4
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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®. 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.


Eligibility criteria: Inclusion Criteria:

* 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®.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From Baseline up to 18 months
Secondary outcomes:
Other outcomes:
measure: Number of Participants With Anti-Recombinant Human Acid Alpha-glucosidase (Anti-rhGAA) Immunoglobulin G (IgG) Antibodies at Month 18
timeFrame: Month 18
measure: Number of Participants With Recombinant Human Acid Alpha-glucosidase (rhGAA) Inhibitory Antibody at Month 18
timeFrame: Month 18
measure: Overall Survival (OS)
timeFrame: From randomization until death or study cut-off whichever comes earlier (up to 18 months)
measure: Number of Participants With Ventilator Use
timeFrame: From Baseline up to 18 months
measure: Left Ventricular Mass (LVM) Z-Score and LVM Index
timeFrame: From Baseline up to 18 months
measure: Gross Motor Disability Assessed by Gross Motor Function Measure-88 (GMFM-88) Score
timeFrame: From Baseline up to 18 months
measure: Motor Development Status Assessed by Alberta Infantile Motor Scale (AIMS) Score
timeFrame: From Baseline up to 18 months
measure: Disability Index Assessed by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) Score
timeFrame: From Baseline up to 18 months
Locations:
city: Louisville
country: United States
state: Kentucky
city: Durham
country: United States
state: North Carolina
city: Salt Lake City
country: United States
state: Utah
city: Norfolk
country: United States
state: Virginia
city: Haifa
country: Israel
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References: