Back to resultsA Phase 1/2 Study of AEB1102 in Patients With Arginase I Deficiency
Primary Purpose
Arginase I Deficiency, Hyperargininemia
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AEB1102
Sponsored by
About this trial
This is an interventional treatment trial for Arginase I Deficiency
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
Sites / Locations
- Stanford University School of Medicine
- University of Florida
- Children's Hospital of Michigan
- Icahn School of Medicine at Mount Sinai
- UTSW
- Seattle Children's Hospital
- The Hospital for Sick Children
- Centro Hospitalar S. Joao
- Great Ormond Street Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AEB1102
Arm Description
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Number of subjects with a decrease from baseline in plasma arginine level
Pharmacokinetic profile including Cmax, AUC, Tmax, T1/2 for each subject
Number of subjects with a decrease from baseline in plasma guanidino compound levels
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02488044
Brief Title
A Phase 1/2 Study of AEB1102 in Patients With Arginase I Deficiency
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
June 2016 (undefined)
Primary Completion Date
February 2019 (Actual)
Study Completion Date
February 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aeglea Biotherapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arginase I Deficiency, Hyperargininemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AEB1102
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AEB1102
Other Intervention Name(s)
Co-ArgI-PEG
Intervention Description
modified human arginase I
Primary Outcome Measure Information:
Title
Number of subjects with adverse events
Description
Includes significant changes in hematology, chemistry and coagulation laboratory studies as well as in physical exam and vital signs
Time Frame
weekly throughout the study, up to 14 weeks
Secondary Outcome Measure Information:
Title
Number of subjects with a decrease from baseline in plasma arginine level
Time Frame
Baseline to 2, 4, 6, 8 weeks
Title
Pharmacokinetic profile including Cmax, AUC, Tmax, T1/2 for each subject
Time Frame
At 15 min, 1, 2, 4, 8, 12, 24, 48, 72, and 120 hours following dose escalation
Title
Number of subjects with a decrease from baseline in plasma guanidino compound levels
Time Frame
Baseline to 2, 4, 6, 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Josie Gayton
Organizational Affiliation
Aeglea Biotherapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
UTSW
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Centro Hospitalar S. Joao
City
Porto
Country
Portugal
Facility Name
Great Ormond Street Hospital
City
London
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
15694174
Citation
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.
Results Reference
background
PubMed Identifier
21633669
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. doi: 10.1593/tlo.10265. Epub 2011 Jun 1.
Results Reference
background
PubMed Identifier
33325055
Citation
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.
Results Reference
derived
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A Phase 1/2 Study of AEB1102 in Patients With Arginase I Deficiency
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