Arginase 1 deficiency Hyperargininemia MedDRA version: 20.0 Level: PT Classification code 10062695 Term: Arginase deficiency System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Pegzilarginase
Product Code: AEB1102
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PEGZILARGINASE
CAS N
Sponsors
Aeglea Biotherapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient must meet all of the following criteria to be enrolled in this study: 1) Completed participation in Study CAEB1102-101A without experiencing any clinically significant AE or other unmanageable drug toxicity that precludes continued dosing 2) After review of the patient’s data from the CAEB1102-101A study, the Investigator and the Sponsor confirm that it is acceptable for the patient to continue dosing with AEB1102 and that the patient continues to meet the following criteria from the 101A study: a) Is male or female: pediatric patients = 2 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A patient is excluded from this study if he/she has: 1) Clinically significant concurrent disease, serious intercurrent illness, or other extenuating circumstances that, in the opinion of the Investigator, would preclude the patient's participation in the study including: a) Had transfusion of = 2 units of RBC within the 60 days before enrollment b) Currently has an active infection requiring systemic treatment c) Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C d) Currently has uncontrolled hyperammonemia (confirmed ammonia = 100 µmol/L) e) Is currently participating in another therapeutic clinical trial f) Has received any investigational agent (other than pegzilarginase) within 30 days of enrollment g) If female, is lactating or breast feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the long-term safety and tolerability of intravenous (IV) or subcutaneous (SC) pegzilarginase administered for up to 3 years in patients with Arginase I deficiency and hyperargininemia; Secondary Objective: • To evaluate the long-term effects of pegzilarginase in patients with Arginase I deficiency and hyperargininemia on sustained reduction of arginine levels • To evaluate the long-term effects of pegzilarginase on plasma guanidinocompounds • To characterize repeat-dose pharmacokinetics (PK) of pegzilarginase administered IV or SC • To evaluate the long-term effects of pegzilarginase on stabilization or improvement of neurological/neuromotor manifestations, using objective measures: o Six-Minute Walk Test o Berg Balance Scale o Gross Motor Function Measure o Modified Ashworth Scale o Purdue Pegboard Test • To evaluate the long-term effects of pegzilarginase on select manifestations of Arginase I deficiency: o Frequency of seizures o Frequency of hyperammonemic episodes o Incidence of disease-related transaminase elevations ; Primary end point(s): Safety and tolerability will be assessed by: • Adverse events (AEs)/serious AEs (SAEs) • Physical examinations • Vital signs • Electrocardiograms (ECGs) • Clinical laboratory studies (serum chemistries, hematology, coagulation, urinalysis) • Low plasma arginine levels associated with clinically significant symptoms • Clinically significant hyperammonemia • Immunogenicity safety measures (levels of anti-drug antibodies [ADAs] and anti-polyethylene glycol [PEG] antibodies) ; Timepoint(s) of evaluation of this end | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: • Changes in plasma arginine levels • Changes in plasma guanidino compound levels • PK parameters • Neurological/neuromotor manifestations, using functional and spasticity measurements: o Six-Minute Walk Test (6-MWT) o Berg Balance Scale (BBS) o Gross Motor Function Measure (GMFM) o Modified Ashworth Scale (MAS) o Purdue Pegboard Test • Other manifestations of Arginase I deficiency o Seizure frequency o Frequency of hyperammonemic episodes, as measured from laboratory evaluations of ammonia levels and relevant AEs o Incidence of transaminase elevations, as measured from laboratory evaluations of liver function tests and relevant AEs ; Timepoint(s) of evaluation of this end point: BL= Baseline; EOT=End of Treatment; Wk= Week; QW=weekly Guanidino compounds: QW 1-24, QW 25-28, Wk 30, 32, 34, 36, 38, 40, 42, 44, 48, prior to dosing every 2nd dose during Wk 52 -140, 144 & EOT PK profile: Wk 1, 8, 24, 25, 26, 27, 28, 32 and Wk 144 Neurological/neuromotor, adaptive behavior, and QOL assessments: BL, Wk 12, 24, 36, 48, 72, 96, 120, 144 & EOT Seizure frequency: BL, QW 1-48, QW 52-144 & EOT | — |
Countries
Canada, Portugal, United Kingdom, United States
Contacts
Public ContactArg1-D Trial Information
Aeglea Biotherapeutics, Inc.
Outcome results
None listed