Principal Investigator: Nicola Longo
Keywords: AEB1102 , Arginase I Deficiency Department: Pediatric Genetics
IRB Number: 00101093 Co Investigator:  
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics
Recruitment Status: Not yet recruiting

Contact Information

Carrie Bailey

Brief Summary

Study Purpose: 

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.


The primary objectives of the study are:
• To evaluate the safety and tolerability of intravenous (IV) administration of AEB1102 in patients with Arginase I deficiency and hyperargininemia

The secondary objectives of the study are:

• To determine the effects of AEB1102 administered IV on plasma arginine concentrations
• To determine the effects of AEB1102 administered IV on plasma guanidino compounds

• To characterize the pharmacokinetic (PK) profile of AEB1102 administered IV

Exploratory Objectives:
• To evaluate the impact of temporary interruptions of AEB1102 administered IV (between Parts 1 and 2) on safety, tolerability, and certain pharmacodynamic (PD)/efficacy biomarkers, including reversibility of changes in plasma levels of arginine
• To examine the onset, magnitude, and reversibility of changes in exploratory biomarkers including changes in additional amino acids (ornithine, glutamine, leucine, isoleucine, and valine), and blood urea nitrogen after IV administration of AEB1102.
• To evaluate the effects of AEB1102 administered IV as measured by
o Neurocognitive, developmental, and quality of life (QOL) measures:
 Wechsler Abbreviated Scale of Intelligence-II;
 Wechsler Preschool and Primary Scale of Intelligence-IV;
 Bayley Scales of Infant Development-III;
 Hopkins Verbal Learning Test–Revised;
 Atlantis subtest on the Kaufman Assessment Battery for Children-II;
 Purdue Pegboard;
 Adaptive Behavior Assessment System, 3rd Edition;
 Promis Parent Proxy Profile, Promis Pediatric Profile, Promis-29;
 PedsQL
o Neurological manifestations, utilizing functional and spasticity measures:
 Berg Balance Scale
 Modified Ashworth Scale
 Gross Motor Function Measures
 Six-Minute Walk Test

 Frequency of seizures
o Growth Parameters
o Hepatic and other biochemical measures


Inclusion Criteria

A patient must meet all of the following criteria to be enrolled in this study:
1. Is male or female: Pediatric patients ≥ 2 to < 18 years of age; and adult patients ≥ 18 years of age.
2. Has documented diagnosis of Arginase I deficiency, with:
• Hyperargininemia: plasma arginine levels consistently ≥ 2-times the upper limit of normal (ULN) (> 250 μM)

• Known mutation in the Arginase I gene
• Known decrease in arginase activity (< 5%) in red blood cells (RBCs)
3. Has adequate organ function defined as follows:
a. Bone Marrow: Hemoglobin ≥10 g/dL; absolute neutrophil count ≥ 1.5x109/L; platelet count ≥ 100,000/μL
b. Hepatic: transaminase levels (aspartate aminotransferase/alanine aminotransferase ≤ 2.5-times ULN; total bilirubin ≤ 2.0 mg/dL
c. Renal: serum creatinine < 1.5x ULN
4. If female and of child-bearing potential, has a negative serum pregnancy test within 7 days before enrollment.
5. If 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.
6. Patient or legal guardian is able and willing to provide written informed consent and where required assent, 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

1. Had transfusion of ≥ 2 units of RBC within the 60 days before enrollment
2. Currently has an active infection requiring systemic treatment
3. Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
4. Had severe hyperammonemia requiring hospitalization within the 14 days before enrollment. Had more than 1 episode of hyperammonemia requiring hospitalization within the 30 days prior to enrollment.

5. Currently has uncontrolled hyperammonemia (ammonia ≥ 100 μmol/L)
6. Currently has any comorbid condition that in the opinion of the investigator might compromise the patient’s safety, might interfere with participation in the trial, or might interfere with the interpretation of trial results
7. Is currently participating in another therapeutic clinical trial
8. Has received any investigational agent within 30 days of enrollment
9. Has a history of hypersensitivity to polyethylene glycol (PEG) or any other component of the AEB1102 (Co-ArgI-PEG) formulation
10. If female, is lactating or breast feeding

1. Did not experience any safety or tolerability event in Part 1 which would preclude continued participation and dosing of AEB1102