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
    • Intelligence:
      • Wechsler Adult Intelligence Scale IV
      •  Wechsler Intelligence Scale for Children V
      • Wechsler Preschool and Primary Scale of Intelligence IV
      • Bayley Scales of Infant Development III 
    • Memory:
      • Rey Auditory Verbal Learning Test
      • Atlantis subtest on the Kaufman Assessment Battery for Children II
    • Attention: 
      • Test of Variables of Attention (version 9)
    • Adaptive Behavior:
      • Vineland Adaptive Behavior Scales II
    • Development: 
      • Growth parameters (length/stature, weight, head circumference) 
    • Quality of Life: 
      • Patient-Reported Outcomes Measurement Information System (PROMIS) Parent Proxy Profile, PROMIS Pediatric Profile, PROMIS-29 or the PedsQL Measurement Model for the Pediatric Quality of Life Inventory
      • 36-Item Short Form Health Survey (SF-36)
      • Short Form Zarit Burden Interview (ZBI-12)
    • Neurological manifestations, utilizing functional and spasticity measures:
      • Six-Minute Walk Test
      • Berg Balance Scale
      • Gross Motor Function Measures
      • Modified Ashworth Scale
      • Purdue Pegboard Test
    • Frequency of seizures
    • Frequency of hyperammonemic episodes
    • Incidence of disease-related transaminase elevations


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 from one or more of 3 baseline samples > 250 μM or 2 of 3 baseline samples > 200 μM (note: 2 of the 3 samples can be collected by home health care personnel)

                    AND EITHER
• 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; WBC >3.0 × 109/L; platelet count ≥ 100,000/μL
b. Hepatic (bilirubin): Total bilirubin ≤ 2.0 × upper limit of normal (ULN)
c. Hepatic (transaminases): Either
 Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN
 AST and/or ALT > 3.0 × ULN but both ≤ 5 × ULN, and in the opinion of the Investigator, related to Arginase 1 deficiency
 Renal: serum creatinine < 1.5 × 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 unstable hyperammonemia requiring hospitalization within the 14 days before

5. Currently has any comorbid condition or laboratory abnormality 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
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