Pompe Disease - acid maltase deficiency or glycogen storage disease type II. MedDRA version: 20.0 Level: LLT Classification code 10036143 Term: Pompe's disease System Organ Class: 100000004850
Conditions
Sponsors
Amicus Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohort 1: 1. Male and female subjects between 18 and 65 years of age, inclusive. 2. Subject must provide signed informed consent prior to any study-related procedures. 3. Subjects of childbearing potential must agree to use medically accepted methods of contraception during the study and for 90 days after last co-administration of ATB200 and AT2221. 4. Subject has a diagnosis of Pompe disease based on documented deficiency of GAA enzyme activity or by GAA genotyping. 5. Subject has received ERT with alglucosidase alfa (myozyme/lumizyme) for the previous 2 to 6 years inclusive. 6. Subject is currently receiving alglucosidase alfa (myozyme/lumizyme) at a frequency of once every other week. 7. Subject has received and completed the last two infusions without a drug-related adverse event resulting in dose interruption. 8. Subject must be able to walk 200 and 500 meters on the 6MWT. 9. Upright FVC must be 30% to 80% of predicted normal value. Cohort 2: 10. Male and female subjects between 18 and 65 years of age, inclusive. 11. Subject must provide signed informed consent prior to any study-related procedures. 12. Subjects of childbearing potential must agree to use medically accepted methods of contraception during the study and for 90 days after last co-administration of ATB200 and AT2221. 13. Subject has a diagnosis of Pompe disease based on documented deficiency of GAA enzyme activity or by GAA genotyping. 14. Subject has received ERT with alglucosidase alfa (myozyme/lumizyme) for =2 years. 15. Subject is currently receiving alglucosidase alfa (myozyme/lumizyme) at a regular or set frequency. 16. Subject has received and completed the last two infusions without a drug-related adverse event resulting in dose interruption. 17. Subject must be completely wheelchair-bound and unable to walk unassisted. Cohort 3: 18. Male and female subjects between 18 and 65 years of age, inclusive. 19. Subject must provide signed informed consent prior to any study related procedures. 20. Subjects of childbearing potential must agree to use medically accepted methods of contraception during the study and for 90 days after last coadministration of ATB200 and AT2221. 21. Subject has a diagnosis of Pompe disease based on documented deficiency of GAA enzyme activity or by GAA genotyping. 22. Subject must be able to walk between 200 to 500 meters on the 6MWT. 23. Upright FVC must be 30% to 80% of predicted normal value. Cohort 4: 24.Male and female subjects between 18 and 75 years of age, inclusive 25.Subject must provide signed informed consent prior to any study related procedures 26.Subject has documented 6MWT on three separate occasions, each at least six months apart with at least two values in the past three years 27.Subjects of childbearing potential must agree to use medically accepted methods of contraception during the study and for 90 days after last co-administration of ATB200 and AT2221 28. Subject has a diagnosis of Pompe disease based on documented deficiency of GAA enzyme activity or by GAA genotyping 29. Subject has received ERT for the previous = 7 years 30. Subject is currently receiving alglucosidase alfa (Myozyme/Lumizyme) at a frequency of once every other week 31. Subject has received and completed the last 2 infusions without a drug-related AE resulting in dose interruption 32. Subject must be able to walk between 75 and 600 meters on the 6MWT 33. Upright FVC must be 30% to 85% of predicted norm
Exclusion criteria
Exclusion criteria: Cohort 1, 2, 3, 4: - Subject has received treatment with prohibited medications within 30 days or 5 half lives of the therapy treatment, whichever is longer prior to the Baseline Visit. - Subject, if female, is pregnant or breastfeeding at screening. - Subject, whether male or female, is planning to conceive a child during the study. - Subject has a medical or any other extenuating condition or circumstance that may, in the opinion of the investigator or the medical monitor, pose an undue safety risk to the subject or compromise his/her ability to comply with protocol requirements. - Subject has a history of allergy or sensitivity to miglustat or other iminosugars. - Subject with active bronchial asthma. All subjects with autoimmune disease must be discussed with the Amicus Medical Monitor - Subject with active systemic autoimmune disease such as lupus, scleroderma, or rheumatoid arthritis. All subjects with autoimmune disease must be discussed with the Amicus Medical Monitor Cohort 1: - Subject requires invasive ventilatory support. - Subject uses noninvasive ventilatory support =6 hours a day while awake. - Subject has a history of anaphylaxis to alglucosidase alfa. - Subject has a history of high sustained anti-rhGAA antibodies. -Subject has received any investigational therapy including adjunctive therapy for Pompe disease, other than alglucosidase alfa within 30 days prior to the Baseline Visit, or anticipates doing so during the study. Cohort 2: - Subject has a history of anaphylaxis to alglucosidase alfa. - Subject has a history of high sustained anti-rhGAA antibodies. - Subject has received any investigational therapy including adjunctive therapy for Pompe disease, other than alglucosidase alfa within 30 days prior to the Baseline Visit, or anticipates doing so during the study. Cohort 3 - Subject has received any enzyme replacement therapy, including alglucosidase alfa at any time, or any investigational therapy for Pompe disease within 30 days prior to the Baseline Visit, or anticipates doing so during the study. - Subject requires invasive ventilatory support. - Subject uses noninvasive ventilatory support =6 hours a day while awake. Cohort 4 - Subject requires invasive ventilatory support - Subject uses noninvasive ventilatory support = 6 hours a day while awake - Subject has a history of anaphylaxis to alglucosidase alfa - Subject has a history of high sustained anti-rhGAA antibodies - Subject has received any investigational therapy including adjunctive therapy for Pompe disease, other than alglucosidase alfa within 30 days prior to the Baseline Visit, or anticipates doing so during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of single-ascending doses of intravenously (IV) infused ATB200. To evaluate the safety and tolerability of single-ascending doses of IV infused ATB200 as a fixed dose, co-administered with ascending oral doses of AT2221. To characterize the pharmacokinetics (PK) of single-ascending doses of IV infused ATB200. To characterize the single- and multiple-dose PK of IV infused 20 mg/kg ATB200 when co-administered with oral 130 mg or 260 mg AT2221. To characterize the PK of single- and multiple-oral doses of 130 mg or 260 mg AT2221 when co-administered with IV infused ATB200.;Secondary Objective: Evaluate long-term efficacy of 20mg/kg IV infused ATB200 as a fixed dose co-administered with oral 260mg AT2221 in all subjects from Stage 3 Evaluate the long-term safety & tolerability of 20 mg/kg of IV infused ATB200 as a fixed dose co-administered with oral 260mg AT2221 in all subjects from Stage 3 Characterize single & multiple dose PK of plasma rhGAA activity and total rhGAA protein following IV infused 20mg/kg ATB200 as a fixed dose co-administered with oral 260mg AT2221 in ERT-naïve subjects Characterize the single & multiple-dose PK of plasma AT2221 following 20mg/kg of IV infused ATB200 co-administered with oral 260 mg AT2221 in ERT-naïve subjects Exploratory: Anti-rhGAA antibody titersantibodies (total and neutralizing) Cross-reactivity of anti-rhGAA antibodies to alglucosidase alfa Pro-inflammatory cytokines and other biomarkers of immune system activation PD markers Impact of anti-rhGAA antibodies on plasma GAA total protein exposures;Primary end point(s): Safety: Identification and counts of treatment-emergent SAEs, including IARs Changes from baseline in 12-lead ECG Changes from baseline in clinical safety laboratory evaluations: serum chemistry, hematology, and urinalysis Changes in PEs Changes from baseline in vital signs Changes from baseline in serum CK PK for subjects from Cohort 1: Plasma GAA activ | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Functional: • For ambulatory subjects: change and percent change from Baseline to 6-month assessment in Gower's Maneuver, 4-stair-climb, 6MWT, 10MWT, GSGC score, TUG, muscle strength tests (MRC and hand-held dynamometer [for both upper and lower limbs]), and pulmonary function tests (FVC, MIP, MEP, and SNIP [for subjects without invasive ventilatory support]). • For nonambulatory subjects: change and percent change from Baseline to 6 month assessment in muscle strength tests (MRC and hand-held dynamometer [upper limbs only]) and pulmonary function tests (FVC, MIP, MEP, and SNIP [for subjects without invasive ventilatory support]) Patient-Reported Outcomes: • Change and percent change from Baseline to 6 months in FSS, RHS, and R-PAct Scale. Impression of Change: • PGIC and SGIC PK parameters for subjects from Cohort 1 and 3: • Plasma GAA activity levels and total GAA protein concentration PK parameters: Cmax, tmax, AUC0-t, AUC0-8, t½, and CLT. • Plasma GAA activity and total GAA protein ratios for Cmax, AUC0-t, and AUC0-8 for single-dose versus multiple-dose • Plasma AT2221 PK parameters: Cmax, tmax, AUC0-t, AUC0-8, t½, CLT/F, and Vz/F. • Plasma AT2221 Cmax, AUC0-t, and AUC0-8 ratios for single-dose versus multiple-dose. • Single-dose plasma GAA activity, total protein and AT2221 Cmax, AUC0-t, and AUC0-8 ratios for subjects from Cohort 3 versus subjects from Cohort 1 following 20 mg/kg ATB200 alone, 20 mg/kg ATB200 + 130 mg AT2221 single-dose, and 20 mg/kg ATB200 + 260 mg AT2221 single-dose. ;Timepoint(s) of evaluation of this end point: n/a | — |
Countries
Australia, Germany, Netherlands, United Kingdom, United States
Contacts
Public ContactJacquelyn Wright
Amicus Therapeutics, Inc.
Outcome results
None listed