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

NCT02488044 | Completed Phase 1 DMC

• 1 other identifier: CAEB1102-101A
• Study Type: interventional
• Target: 16
• Locations: 4 countries
• Sites: 9

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.

Conditions

Arginase I Deficiency; Hyperargininemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (1)

AEB1102

EXPERIMENTAL

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

Interventions

AEB1102 DRUG

modified human arginase I

Also known as: Co-ArgI-PEG

AEB1102

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Aeglea Biotherapeutics: lead

Study Sites (9)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

UTSW

Dallas, Texas, 75390, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Centro Hospitalar S. Joao

Porto, Portugal

Location

Great Ormond Street Hospital

London, United Kingdom

Location

Related Publications (3)

• Crombez EA, Cederbaum SD. Hyperargininemia due to liver arginase deficiency. Mol Genet Metab. 2005 Mar;84(3):243-51. doi: 10.1016/j.ymgme.2004.11.004. Epub 2004 Dec 19.

  PMID: 15694174 BACKGROUND

• Glazer ES, Stone EM, Zhu C, Massey KL, Hamir AN, Curley SA. Bioengineered human arginase I with enhanced activity and stability controls hepatocellular and pancreatic carcinoma xenografts. Transl Oncol. 2011 Jun;4(3):138-46. doi: 10.1593/tlo.10265. Epub 2011 Jun 1.

  PMID: 21633669 BACKGROUND

• Diaz GA, Schulze A, McNutt MC, Leao-Teles E, Merritt JL 2nd, Enns GM, Batzios S, Bannick A, Zori RT, Sloan LS, Potts SL, Bubb G, Quinn AG. Clinical effect and safety profile of pegzilarginase in patients with arginase 1 deficiency. J Inherit Metab Dis. 2021 Jul;44(4):847-856. doi: 10.1002/jimd.12343. Epub 2021 Jan 26.

  PMID: 33325055 DERIVED

MeSH Terms

Conditions

Hyperargininemia

Condition Hierarchy (Ancestors)

Urea Cycle Disorders, Inborn; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Josie Gayton

  Aeglea Biotherapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2015
• First Posted: July 2, 2015
• Study Start: June 1, 2016
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: June 12, 2019

Record last verified: 2019-06

Locations

GB (1); US (6); PT (1); CA (1)