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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1/2 Open-label Study in Patients With Arginase I Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous AEB1102

Conditions
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Arginase I Deficiency, Hyperargininemia

Intervention / Treatment
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* Drug: AEB1102


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AEB1102<br>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. | Drug: AEB1102<br>* modified human arginase I<br>* Other names: Co-ArgI-PEG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events | Includes significant changes in hematology, chemistry and coagulation laboratory studies as well as in physical exam and vital signs | weekly throughout the study, up to 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |