First in human study in participants with Pompe disease
Research type
Research Study
Full title
AN OPEN-LABEL, FIXED-SEQUENCE, ASCENDING-DOSE, FIRST-INHUMAN 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
IRAS ID
196801
Contact name
Mark Roberts
Contact email
Sponsor organisation
Amicus Therapeutics, Inc.
Eudract number
2015-004798-34
Duration of Study in the UK
2 years, 3 months, 0 days
Research summary
Research Summary
People who have Pompe disease, were born with a defect in the coding information (genetic mutation), which results in lower than normal levels of an enzyme called acid alpha-glucosidase (GAA). The GAA enzyme is important because it helps the body break down a form of glycogen, a type of stored sugar. When glycogen is not broken down properly, it builds up and the body’s muscle cells are not able to function normally. This causes the symptoms of Pompe disease. Pompe disease affects about 1 in 40,000 people globally.\n\nPatients who have Pompe disease are invited to participate in the study. The purpose of this study is to find out if new investigational medications called ATB200 and AT2221 are safe and can help adults with Pompe disease. This is the first research study which tests ATB200 and AT2221 in people with Pompe disease.\n\nParticipants will receive the investigational medications ATB200 alone or in combination with AT2221. ATB200 will be given into a vein in the arm (intravenously). In Stage 2 participants will be given two medications, ATB200 (intravenously) and AT2221 by mouth, with water (orally). Everyone will receive ATB200 and AT2221. Stage 1 and 2 will enter into a long-term extension stage (Stage 3). \nThis is an open label study which means that the participant and their doctor know what medication and dose the participant is getting. \n\nThis study aims to evaluate the effect of a better targeted rhGAA (ATB200) given together with AT2221 which has been shown to increase the stability of ERT resulting in the delivery of more active enzyme to the target area.\n\nApproximately 18 patients will take part in this study at approximately 14 sites worldwide. The entire study will take place over a total of about 2 years and 18 weeks.
Summary of Results
In Stages 1 and 2 of this study, cipaglucosidase alfa 20 mg/kg co-administered with 260 mg miglustat was demonstrated to be well-tolerated. The PK of cipaglucosidase alfa with and without miglustat was well characterized over all dose regimens evaluated during the study. Overall, the PK, PD, safety, and efficacy results from this study confirmed the 20 mg/kg + 260 mg dose regimen combination for treatment co-administration in the pivotal Phase 3 study in adult subjects with LOPD.
Data from Stages 3 and 4 of this study confirmed that co-administration of 20 mg/kg IV-infused cipaglucosidase alfa and 260 mg miglustat demonstrated clinically meaningful improvements in motor function (Schrover, Evans et al. 2017), improvements in muscle strength, and stability or improvements in PFTs in ERT-naïve and ERT-experienced subjects. These improvements were generally sustained above baseline values through 84 months of treatment and supported by PRO, SGIC, and PGIC results. The combination was considered to be generally safe and well-tolerated in subjects with Pompe disease. The overall benefit-risk assessment was considered favorable based on these data.REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
16/EE/0163
Date of REC Opinion
1 Aug 2016
REC opinion
Further Information Favourable Opinion