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

Hyperargininemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02488044
• Other study ID #: CAEB1102-101A
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 2016
• Est. completion date: February 2019

Study information

• Verified date: June 2019
• Source: Aeglea Biotherapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: February 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arginase I Deficiency
• Hyperargininemia

Intervention

Drug:
• AEB1102
modified human arginase I

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario
Portugal	Centro Hospitalar S. Joao	Porto
United Kingdom	Great Ormond Street Hospital	London
United States	UTSW	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	University of Florida	Gainesville	Florida
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Seattle Children's Hospital	Seattle	Washington
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Aeglea Biotherapeutics

Countries where clinical trial is conducted

United States,  Canada,  Portugal,  United Kingdom, 

References & Publications (2)

Crombez EA, Cederbaum SD. Hyperargininemia due to liver arginase deficiency. Mol Genet Metab. 2005 Mar;84(3):243-51. Epub 2004 Dec 19. Review. — View Citation

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. Epub 2011 Jun 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of subjects with a decrease from baseline in plasma arginine level		Baseline to 2, 4, 6, 8 weeks
Secondary	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
Secondary	Number of subjects with a decrease from baseline in plasma guanidino compound levels		Baseline to 2, 4, 6, 8 weeks