This study has been transitioned to CTIS with ID 2023-505170-15-00 check the CTIS register for the current data. The objective of the study is to assess the long-term safety and efficacy of intravenous ATB200 co-administration with oral AT2221 in…
ID
Source
Brief title
Condition
- Musculoskeletal and connective tissue disorders congenital
- Musculoskeletal and connective tissue disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The long-term safety profile of ATB200/AT2221 will be characterized using
incidence of treatment-emergent adverse events (TEAEs), serious adverse events
(SAEs), and AEs leading to discontinuation of study drug, frequency and
severity of immediate and late IARs, and any abnormalities noted in other
safety assessments (eg, clinical laboratory tests, ECGs, vital signs).
Immunogenicity to ATB200 will also be described.
Secondary outcome
Efficacy endpoints are as follows:
• change from baseline in 6-minute walk distance (6MWD)
• change from baseline in 6MWD (% predicted)
• change from baseline in sitting FVC (% predicted)
• change from baseline in the manual muscle test score for the lower extremities
• change from baseline in the total score for the PROMIS - physical function
• change from baseline in the total score for the PROMIS - fatigue
• change from baseline in the following variables related to motor function:
* GSGC total score
* time to complete the 10-meter walk (ie, assessment of gait) of the GSGC test
* time to complete the 4-stair climb of the GSGC test
* time to complete the Gower*s maneuver of the GSGC test
* time to arise from a chair as part of the GSGC test
* change from baseline in the time to complete the TUG test
• change from baseline in the following variables related to muscle strength:
* manual muscle test score for the upper extremities
* manual muscle test total score (upper and lower extremities combined)
* quantitative muscle test value (kg) for the upper extremities
* quantitative muscle test value (kg) for the lower extremities
* quantitative muscle test total value (kg) (upper and lower extremities
combined)
• change from baseline in the following variables from patient-reported outcome
measures:
* total score for the PROMIS - dyspnea
* total score for the PROMIS - upper extremity
* R-PAct Scale total score
* EQ-5D-5L health status
• actual value of the subject*s functional status (improving, stable, or
declining) pertaining to the effects of study drug in the following areas of
life, as measured by the SGIC:
* overall physical well-being
* effort of breathing
* muscle strength
* muscle function
* ability to move around
* activities of daily living
* energy level
* level of muscular pain
• actual value of the subject*s functional status (improving, stable, or
declining), as measured by the PGIC
• change from baseline in the following measures of pulmonary function, as
follows:
* sitting SVC (% predicted)
* MIP (cmH2O)
* MIP (% predicted)
* MEP (cmH2O)
* MEP (% predicted)
* SNIP (cmH2O)
Pharmacodynamic endpoints are as follows:
• change from baseline in serum CK level
• change from baseline in urinary Hex4 level
Background summary
Pompe disease is a disease that results in loss of muscle function and
strength. This is because patients with Pompe disease are born with a gene
mutation in a specific enzyme. Different genes carry the information that
determines different characteristics of people, and this is why there so many
different people with different hair and eye colours. In people with Pompe
disease there is a mutation in one of these genes and therefore you will
develop lower levels of that enzyme causing your muscle to not function
properly.
Enzyme replacement therapy has become available for all patients to replace the
defected enzyme with *healthy* enzyme. It has been shown that the magnitude and
duration of therapeutic response with continuing therapy vary among individual
patients. The current therapy, at best, may offer improvements for a limited
duration followed by a slow decline of therapeutic effectiveness. The
co-administration of ATB200 with AT2221 is designed to address these
limitations of current therapy.
Study objective
This study has been transitioned to CTIS with ID 2023-505170-15-00 check the CTIS register for the current data.
The objective of the study is to assess the long-term safety and efficacy of
intravenous ATB200 co-administration with oral AT2221 in adult subjects with
late-onset Pompe disease.
Study design
This is a multicenter, international open-label extension study of
ATB200/AT2221 in adult subjects with late-onset Pompe disease (LOPD) who
completed Study ATB200-03.
Intervention
ATB200/AT2221 will be co-administered as follows: AT2221 260 mg (4 × 65-mg oral
capsules) for subjects weighing >= 50 kg and 195 mg (3 × 65-mg oral capsules)
for subjects weighing >= 40 kg to < 50 kg, followed approximately 1 hour later
by ATB200 20 mg/kg (reconstituted lyophilized drug product, 105 mg/vial),
administered over a 4-hour intravenous [IV] infusion. The ATB200/AT2221
combination regimen will be administered every 2 weeks. Note: Subjects are
required to fast at least 2 hours before and 2 hours after administration of
AT2221.
Study burden and risks
ATB200/AT2221 has proven overall to be generally safe and relatively well
tolerated. Alternative treatments provide initial benefit to patients with
Pompe disease. The magnitude and duration of therapeutic response with
continuing therapy varies among individual subjects and, at best, may offer
improvement in measures of muscle function, strength, and respiratory function
for a finite duration, ie, 2 to 3 years in most subjects, followed by a slow
decline in these parameters. These alternative treatments may themselves be
associated with significant risks. A monthly review for safety signals is part
of routine pharmacovigilance.
Hulfish Street 47
Princeton NJ 08542
US
Hulfish Street 47
Princeton NJ 08542
US
Listed location countries
Age
Inclusion criteria
1. Subject must provide signed informed consent prior to any study-related
procedures being performed. If the subject is under 20 years of age, the
subject must provide written informed consent.
2. Subject must have completed Study ATB200-03.
Note: Subjects who were forced to withdraw from Study ATB200-03 for a
logistical reason not related to the efficacy or safety of ATB200/AT2221 (eg,
hospitalization for a car accident or emergency surgery) and which resulted in
several consecutive missed doses may be eligible to participate in this study
upon approval by the Amicus medical monitor.
3. Female subjects of childbearing potential and male subjects must agree to
use medically accepted methods of contraception during the study and for 90
days after the last dose of study drug.
Exclusion criteria
1. Subject plans to receive gene therapy or participate in another
interventional study for Pompe disease.
2. Subject has a hypersensitivity to any excipients in ATB200 or ATB2221 or
medical condition or any other extenuating circumstance that may, in the
opinion of the investigator or medical monitor, pose an undue safety risk to
the subject or may compromise his/her ability to comply with or adversely
impact protocol requirements. This includes clinical depression (as diagnosed
by a psychiatrist or other mental health professional) with uncontrolled or
poorly controlled symptoms.
3. Subject, if female, is pregnant or breastfeeding.
4. Subject, whether male or female, is planning to conceive a child during the
study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-505170-15-00 |
| EudraCT | EUCTR2019-000954-67-NL |
| ClinicalTrials.gov | NCT04138277 |
| CCMO | NL71554.078.20 |