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

June 11, 2019 updated by: Aeglea Biotherapeutics

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • The Hospital for Sick Children
  • Portugal
      • Porto, Portugal
        • Centro Hospitalar S. Joao
  • United Kingdom
      • London, United Kingdom
        • Great Ormond Street Hospital
  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University School of Medicine
    • Florida
      • Gainesville, Florida, United States, 32611
        • University of Florida
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai
    • Texas
      • Dallas, Texas, United States, 75390
        • UTSW
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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.
Drug: AEB1102
modified human arginase I
Other Names:
  • Co-ArgI-PEG

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of subjects with adverse events
Time Frame: weekly throughout the study, up to 14 weeks
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 Outcome Measures

Outcome Measure
Time Frame
Number of subjects with a decrease from baseline in plasma arginine level
Time Frame: Baseline to 2, 4, 6, 8 weeks
Baseline to 2, 4, 6, 8 weeks
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
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
Time Frame: Baseline to 2, 4, 6, 8 weeks
Baseline to 2, 4, 6, 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aeglea Biotherapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2016

Primary Completion (ACTUAL)

February 1, 2019

Study Completion (ACTUAL)

February 1, 2019

Study Registration Dates

First Submitted

June 29, 2015

First Submitted That Met QC Criteria

June 30, 2015

First Posted (ESTIMATE)

July 2, 2015

Study Record Updates

Last Update Posted (ACTUAL)

June 12, 2019

Last Update Submitted That Met QC Criteria

June 11, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAEB1102-101A

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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