A Phase 1/2 Study of AEB1102 in Patients With Arginase I Deficiency

Aeglea BioTherapeutics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Hyperargininemia; Arginase I Deficiency

Treatments: Drug: AEB1102

Study type: Interventional

Funder types: Industry

Identifiers

NCT02488044

CAEB1102-101A

Details and patient eligibility

About

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.

Enrollment: 16 patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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16 participants in 1 patient group

AEB1102

Experimental group

Description:

AEB1102, modified human Arginase I administered IV Part 1 Each patient may receive up to 7 doses given up to every other week over a maximum of 14 weeks. Part 2 Each patient will receive up to 8 weeks of repeat-dose therapy.

Treatment:

Drug: AEB1102