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

NCT ID: NCT02488044

Last Updated: 2019-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2019-02-28

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

AEB1102

Intervention Type: DRUG

modified human arginase I

Interventions

AEB1102

modified human arginase I

Intervention Type: DRUG

Other Intervention Names

Co-ArgI-PEG

Eligibility Criteria

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

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aeglea Biotherapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Josie Gayton

Role: STUDY_DIRECTOR

Aeglea Biotherapeutics, Inc.

Locations

Stanford University School of Medicine

Stanford, California, United States

University of Florida

Gainesville, Florida, United States

Children's Hospital of Michigan

Detroit, Michigan, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

UTSW

Dallas, Texas, United States

Seattle Children's Hospital

Seattle, Washington, United States

The Hospital for Sick Children

Toronto, Ontario, Canada

Centro Hospitalar S. Joao

Porto, , Portugal

Great Ormond Street Hospital

London, , United Kingdom

Countries

United States; Canada; Portugal; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 15694174 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21633669 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33325055 (View on PubMed)

Other Identifiers

CAEB1102-101A

Identifier Type: -

Identifier Source: org_study_id