AN OPEN-LABEL, FIXED-SEQUENCE, ASCENDING-DOSE, FIRST-IN-HUMAN STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND EFFICACY OF INTRAVENOUS INFUSIONS OF ATB200 CO-ADMINISTERED WITH ORAL AT2221 IN ADULT SUBJECTS WITH POMPE DISEASE
- Conditions
- hereditary muscle diseaseneuromuscular disorder10027664
- Registration Number
- NL-OMON50710
- Lead Sponsor
- Amicus Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 2
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 between 200 and 500 meters on the 6MWT
9. Upright forced vital capacity (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 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 co-administration 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 inf
Cohort 1
1. Subject has received any investigational therapy including adjunctive
therapy for Pompe disease, other than alglucosidase alfa within 30 days or 5
half-lives of the therapy or treatment, whichever is longer, prior to the
Baseline Visit, or anticipates doing so during the study
2. Subject has received treatment with prohibited medications (see protocol
section 8.7) within
30 days of the Baseline Visit
3. Subject, if female, is pregnant or breastfeeding at screening
4. Subject, whether male or female, is planning to conceive a child during the
study
5. Subject requires invasive ventilatory support
6. Subject uses noninvasive ventilatory support *6 hours a day while awake
7. 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
8. Subject has a history of anaphylaxis to alglucosidase alfa
9. Subject has a history of high sustained anti-rhGAA antibodies (see Section
10.4)
10. Subject has a history of allergy or sensitivity to miglustat or other
iminosugars
11. Subjects with active systemic autoimmune disease such as lupus,
scleroderma, or rheumatoid arthritis. All subjects with autoimmune disease must
be discussed with Amicus Medical Monitor
12. Subjects with active bronchial asthma. All subjects with bronchial asthma
must be discussed with the Amicus Medical Monitor, Cohort 2
13. Subject has received any investigational therapy including adjunctive
therapy for Pompe disease, other than alglucosidase alfa within 30 days or 5
half-lives of the therapy or treatment, whichever is longer, prior to the
Baseline Visit, or anticipates to do so during the study
14. Subject has received treatment with prohibited medications (see protocol
section 8.7) within
30 days of the Baseline Visit
15. Subject, if female, is pregnant or breastfeeding at screening
16. Subject, whether male or female, is planning to conceive a child during the
study
17. 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
18. Subject has a history of anaphylaxis to alglucosidase alfa
19. Subject has a history of high sustained anti-rhGAA antibodies (see Section
10.4)
20. Subjects has a history of allergy or sensitivity to miglustat or other
iminosugars
21. Subjects 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
22. Subjects with active bronchial asthma. All subjects with bronchial asthma
must be discussed with the Amicus Medical Monitor, Cohort 3
23. Subject has received any enzyme replacement therapy, including
alglucosidase alfa at any time, or any investigational therapy for Pompe
disease within 30 days or 5 half-lives of the therapy or treatment, whichever
is longer, prior to the Baseline Visit, or anticipates doing so during the study
24. Subject has received treatment with prohibited medications within 30 days
of the Baseline Visit
25. Subj
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>* To evaluate the safety and tolerability of single-ascending doses of<br /><br>intravenously (IV) infused ATB200<br /><br>* To evaluate the safety and tolerability of single-ascending doses of IV<br /><br>infused ATB200 as a fixed dose, co-administered with ascending oral doses of<br /><br>AT2221<br /><br>* To characterize the pharmacokinetics (PK) of single-ascending doses of IV<br /><br>infused ATB200<br /><br>* To characterize the single- and multiple dose PK of IV infused 20 mg/kg<br /><br>ATB200 when co-administered with oral 130 mg or 260 mg AT2221<br /><br>* To characterize the PK of single- and multiple-oral doses of 130 mg or 260 mg<br /><br>AT2221 when co-administered with IV infused ATB200</p><br>
- Secondary Outcome Measures
Name Time Method <p>* To evaluate the long-term efficacy of 20 mg/kg of IV infused ATB200 as a<br /><br>fixed dose co-administered with oral 260 mg AT2221 in all subjects from Stage 3<br /><br>* To evaluate the long-term safety and tolerability of 20 mg/kg of IV infused<br /><br>ATB200 as a fixed dose co-administered with oral 260 mg AT2221 in all subjects<br /><br>from Stage 3<br /><br>* To characterize single- and multiple-dose PK of plasma rhGAA activity and<br /><br>total rhGAA protein following IV infused 20 mg/kg ATB200 as a fixed dose<br /><br>co-administered with oral 260 mg AT2221 in enzyme replacement therapy<br /><br>(ERT)-naïve subjects<br /><br>* To characterize the single- and multiple-dose PK of plasma AT2221 following<br /><br>20 mg/kg of IV infused ATB200 co-administered with oral 260 mg AT2221 in<br /><br>ERT-naïve subjects</p><br>