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

Phase 1

Completed

• Conditions: Arginase I Deficiency; Hyperargininemia
• Interventions: Drug: AEB1102

• Registration Number: NCT02488044
• Lead Sponsor: Aeglea Biotherapeutics

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-06-29
• Study First Submitted QC: 2015-06-30
• Study First Posted: 2015-07-02
• Study Start: 2016-06
• Primary Completion: 2019-02
• Study Completion: 2019-02
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-11
• Last Update Posted: 2019-06-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AEB1102	AEB1102	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (9)

University of Florida; 🇺🇸 Gainesville, Florida, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Centro Hospitalar S. Joao; 🇵🇹 Porto, Portugal

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

Stanford University School of Medicine; 🇺🇸 Stanford, California, United States

Children's Hospital of Michigan; 🇺🇸 Detroit, Michigan, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States

UTSW; 🇺🇸 Dallas, Texas, United States

Great Ormond Street Hospital; 🇬🇧 London, United Kingdom