Arginase I Deficiency, Hyperargininemia
Conditions
Brief summary
A Phase 1/2 Open-label Study in Patients with Arginase I Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous AEB1102. This study is designed to evaluate the safety and tolerability of IV administration of AEB1102 for the treatment of pediatric and adult patients with Arginase I deficiency and hyperargininemia. This study will be conducted in 2 parts: Part 1 (Single Ascending Dose Escalation) and Part 2 (Repeated Dosing). Each part will be preceded by a baseline assessment of arginine levels. All patients who participate in Part 1 may continue AEB1102 dosing in Part 2 if they qualify for continued dosing. A data safety monitoring board (DSMB) will provide independent review of study safety data and recommend whether the sponsor should continue the study as planned, modify the study protocol, or discontinue the study.
Interventions
DRUGAEB1102
modified human arginase I
Sponsors
Aeglea Biotherapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented diagnosis of Arginase I deficiency * Adequate organ function: Hgb ≥ 10 g/dL, ANC ≥ 1.5 x 109/L, plt count ≥ 100,000/µL; liver transaminase levels ≤ 2.5x ULN, total bilirubin ≤ 2.0 mg/dL; serum creatinine \<1.5 x ULN * If female and of child-bearing potential, has a negative serum pregnancy test within 7 days before enrollment * If a sexually active (male or female), must be surgically sterile, post-menopausal (female), or must agree to use a physician-approved method of birth control during the study and for a minimum of 30 days after the last study drug administration * Patient or legal guardian is able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures and continuation of prescribed diet without modification) prior to any screening procedures
Exclusion criteria
* Transfusion of ≥ 2 u RBC within 60 days * Active infection requiring systemic treatment * Known infection with HIV, Hep B or Hep C * Severe hyperammonemia requiring hospitalization within 14 days. Had more than one episode of hyperammonemia requiring hospitalization within the 30 days prior to enrollment. * Current uncontrolled hyperammonemia * Has a history of hypersensitivity to PEG or any other component of the AEB1102 (Co-ArgI-PEG) formulation * If female, is lactating or breast feeding PART 2 INCLUSION CRITERION: 1\. Did not experience any safety or tolerability event in Part 1 which would preclude continued participation and dosing of AEB1102
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with adverse events | weekly throughout the study, up to 14 weeks | Includes significant changes in hematology, chemistry and coagulation laboratory studies as well as in physical exam and vital signs |
Secondary
| Measure | Time frame |
|---|---|
| Number of subjects with a decrease from baseline in plasma arginine level | Baseline to 2, 4, 6, 8 weeks |
| Pharmacokinetic profile including Cmax, AUC, Tmax, T1/2 for each subject | At 15 min, 1, 2, 4, 8, 12, 24, 48, 72, and 120 hours following dose escalation |
| Number of subjects with a decrease from baseline in plasma guanidino compound levels | Baseline to 2, 4, 6, 8 weeks |
Countries
Canada, Portugal, United Kingdom, United States
Outcome results
None listed