This is an open-label, fixed-sequence, ascending-dose, first-in-human study to evaluate the safety, tolerability, PK, PD and efficacy of intravenous (IV) ATB200 when co-administered with oral AT2221.
- Conditions
- Pompes 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: 100000004850Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]
- Registration Number
- EUCTR2015-004798-34-NL
- Lead Sponsor
- Amicus Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 32
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 a
Cohort 1, 2, 3, 4:
- Subject has received treatment with prohibited medications within 30 days or 5 half lifes 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method