First-In-Human Study to Evaluate Safety, Tolerability, and PK of Intravenous ATB200 Alone and When Co-Administered With Oral AT2221
- Registration Number
- NCT02675465
- Lead Sponsor
- Amicus Therapeutics
- Brief Summary
This is an international, multi-center, open-label study designed to evaluate if the co-administration of investigational new drugs ATB200 and AT2221 is safe in adults with Pompe disease.
- Detailed Description
This is an open-label, fixed-sequence, ascending-dose, first-in-human study to evaluate the effect of a highly targeted rhGAA (ATB200) co-administered with an enzyme stabilizer (AT2221).
The study aims to evaluate safety, tolerability, pharmacokinetics (PK), efficacy, pharmacodynamics (PD), and immunogenicity of ATB200 co-administered with AT2221.
Stage 1: evaluation of safety, tolerability, and PK following sequential single ascending doses of intravenously infused ATB200
Stage 2: evaluation of safety, tolerability, and PK following single- and multiple-ascending dose combinations of ATB200 and AT2221
Stage 3: evaluation of long term safety, tolerability, and efficacy following 24 month treatment of ATB200 co-administered with AT2221
Stage 4: open-label extension period with functional assessments every 6 months
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
Not provided
- Received treatment with prohibited medications within 30 days of Baseline Visit
- Subject, if female, was pregnant or breastfeeding at screening
- Subject, whether male or female, planned to conceive a child during the study
- Had a medical or any other extenuating condition or circumstance that may, in opinion of investigator, pose an undue safety risk to the subject or compromise his/her ability to comply with protocol requirements
- Had a history of allergy or sensitivity to alglucosidase alfa, miglustat or other iminosugars (Cohorts 1, 2, and 4)
- Required invasive ventilatory support, or used noninvasive ventilatory support ≥ 6 hours a day while awake (Cohorts 1, 3, and 4)
- Had active systemic autoimmune disease such as lupus, scleroderma, or rheumatoid arthritis; subjects with autoimmune disease must have been discussed with the Amicus Medical Monitor
- Had active bronchial asthma; subjects with bronchial asthma must have been discussed with the Amicus Medical Monitor
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ATB200 ATB200 Sequential single ascending doses of intravenously infused ATB200 for 3 dosing periods ATB200 + AT2221 ATB200 ATB200 co-administered with AT2221 (Miglustat) ATB200 + AT2221 AT2221 ATB200 co-administered with AT2221 (Miglustat)
- Primary Outcome Measures
Name Time Method Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug Stage 3 (2 year treatment) and Stage 4 (Extension) combined, (mean = 71 months on treatment) Number of subjects with TEAE, TESAE, and AE leading to discontinuation during the 2 year treatment period and extension (Stage 3 and 4 combined)
Plasma Human Acid α-glucosidase (GAA) Activity Levels as Measured by Maximum Observed Plasma Concentration (Cmax). 18 Weeks Plasma GAA levels (Cmax) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat
Plasma GAA Activity Levels as Measured by Time to Reach the Maximum Observed Plasma Concentration (Tmax). 18 Weeks Plasma GAA levels (Tmax) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat
Plasma GAA Activity Levels as Measured by Area Under the Plasma Drug Concentration-time Curve (AUC). 18 Weeks Plasma GAA levels (AUC) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat
- Secondary Outcome Measures
Name Time Method Change From Baseline in 6-minute Walk Distance (6MWD) Baseline, Month 60 Motor function was measured in ambulatory subjects using 6MWD (meters).
Change From Baseline in Pulmonary Function Tests Baseline, Month 60 Pulmonary function was measured by sitting and supine % predicted forced vital capacity (FVC)
Change From Baseline in Muscle Strength Tests Baseline, Month 60 Muscle strength was measured by total manual muscle test (MMT) score. Total MMT score ranges from 0 to 80 based on all 16 muscle groups, which are right/left shoulder abduction, right/left shoulder adduction, right/left elbow flexion, right/left elbow extension, right/left hip flexion, right/left hip abduction, right/left knee flexion, and right/left knee extension. Higher scores indicate less disease impact on muscle functions.
Change From Baseline in Fatigue Severity Score (FSS) Baseline, Month 60 The Fatigue Severity Score (FSS) consists of 9 questions, each scored on a scale from 1 ("completely disagree") to 7 ("completely agree"). The total score ranges from 9 to 63, with higher values representing higher level of fatigue due to the disease condition.
Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1) Baseline, Month 60 The Subject's Global Impression of Change overall physical wellbeing (question 1) is scored on a 7-point rating scale. Improved = response of 5 or higher, No change = response of 4, and Declined = response of 3 or lower.
Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC]) Baseline, Month 60 The Physician's Global Impression of Change overall physical wellbeing is scored on a 7-point rating scale. Improved = response of 5 or higher, No change = response of 4, and Declined = response of 3 or lower.
Trial Locations
- Locations (19)
Neuromuscular Research Centre
🇺🇸Phoenix, Arizona, United States
University of California Irvine
🇺🇸Orange, California, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Emory University Division of Medical Genetics
🇺🇸Decatur, Georgia, United States
Infusion Associates
🇺🇸Grand Rapids, Michigan, United States
Great Falls Clinic, LLP
🇺🇸Great Falls, Montana, United States
Rutgers New Jersey Medical School
🇺🇸Newark, New Jersey, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Perelman Center for Advanced Medicine
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
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