first-in-human study to evaluate safety, tolerability, and pk of intravenous atb200 alone and when co-administered with oral at2221

Conditions: Pompe Disease

Summary: this study is an international, multi-center, study of pompe disease patients that are currently receiving enzyme-replacement therapy (ert). the purpose of this study is to find out if the co-administration of investigational new drugs atb200 and at2221 is safe in adults with pompe disease.

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 a chaperone (at2221). the study aims to evaluate safety, tolerability, pharmacodynamics (pd), and immunogenicity of atb200 co-administered with at2221. the study will be conducted in 3 stages. in stage 1, safety, tolerability, and pk will be evaluated following sequential single ascending doses of intravenously infused atb200. in stage 2, safety, tolerability, and pk will be evaluated following single- and multiple-ascending dose combinations of atb200 and at2221. in stage 3, long term safety and efficacy will be assessed following 24 month treatment of atb200 co-administered with at2221 (miglustat) in stage 4, treatment period will begin at the end of stage 3 and will continue as open label extension until commercialization, study discontinuation or subject withdrawal, with functional assessments every 6 months no muscle biopsies will be performed in this study.

Eligibility criteria:
key inclusion criteria: * male and female subjects between 18 and 75years of age, inclusive * diagnosis of pompe disease enzyme replacement therapy (ert)-experienced subject (ambulatory): * has received ert with alglucosidase alfa for the previous 2-6 years, inclusive * subject is currently receiving alglucosidase alfa (myozyme/lumizyme), at a frequency of once every other week * must be able to walk 200-500 meters on the 6-minute walk test (6mwt ) * has upright forced vial capacity (fvc) 30% to 80% of predicted normal value ert-experienced subjects (non-ambulatory): * has received ert with alglucosidase alfa (myozyme/lumizyme) for ≥2 years * is wheelchair-bound ert-naïve subjects (ambulatory): * must be able to walk 200-500 meters on the 6mwt * has upright fvc must be 30% to 80% of predicted normal value * subject has never received alglucosidase alfa enzyme replacement therapy (ert)-experienced subject (ambulatory): * has received ert with alglucosidase alfa for \>7years, inclusive * subject is currently receiving alglucosidase alfa (myozyme/lumizyme), at a frequency of once every other week * must be able to walk 200-500 meters on the 6-minute walk test (6mwt ) * has upright forced vial capacity (fvc) 30% to 80% of predicted normal value exclusion criteria: * subject has received treatment with prohibited medications within 30 days of baseline visit * subject, if female, is pregnant or breastfeeding at screening * subject, whether male or female, planning to conceive a child during the study * subject has 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 * subject has a history of allergy or sensitivity to miglustat or other iminosugars * 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 * subjects with active bronchial asthma. all subjects with bronchial asthma must be discussed with the amicus medical monitor

Keywords: pompe, rhgaa