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    Summary
    EudraCT Number:2017-003851-45
    Sponsor's Protocol Code Number:CAEB1102-101A
    National Competent Authority:Portugal - INFARMED
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-01-12
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedPortugal - INFARMED
    A.2EudraCT number2017-003851-45
    A.3Full title of the trial
    A Phase 1/2 Open-label Study in Patients with Arginase 1 Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous AEB1102
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 1/2 Open-label Study in Patients with Arginase 1 Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous AEB1102
    A.4.1Sponsor's protocol code numberCAEB1102-101A
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02488044
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAeglea Biotherapeutics, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAeglea Biotherapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAeglea Biotherapeutics, Inc.
    B.5.2Functional name of contact pointArg1-D Trial Information
    B.5.3 Address:
    B.5.3.1Street Address901 S. MoPac Expressway,Barton Oaks Plaza, Suite 250
    B.5.3.2Town/ cityAustin, TX
    B.5.3.3Post code78746
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1855509 9921
    B.5.6E-mailarg1dtrialinfo@aegleabio.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/16/1701
    D.3 Description of the IMP
    D.3.1Product namePegzilarginase
    D.3.2Product code AEB1102
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPegzilarginase
    D.3.9.1CAS number 1659310-95-8
    D.3.9.2Current sponsor codeAEB1102
    D.3.9.3Other descriptive nameCo-Arg1-PEG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Arginase 1 deficiency
    Hyperargininemia
    E.1.1.1Medical condition in easily understood language
    Arginase deficiency
    Hyperargininemia
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10062695
    E.1.2Term Arginase deficiency
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the safety and tolerability of intravenous (IV) administration of AEB1102 in patients with Arginase I deficiency and hyperargininemia
    E.2.2Secondary objectives of the trial
    1) To determine the effects of AEB1102 administered IV on plasma arginine concentrations
    2)To determine the effects of AEB1102 administered IV on plasma guanidino compounds
    3) To characterize the pharmacokinetic (PK) profile of AEB1102 administered IV
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    A patient must meet all of the following criteria to be enrolled in this study:
    PART 1
    1. Is male or female: pediatric patients ≥ 2 to < 18 years of age and adult patients ≥ 18 years of age
    2. Has documented diagnosis of Arginase 1 deficiency, with:
    • Hyperargininemia: plasma arginine levels from one or more of 3 baseline samples > 250 μM or 2 of 3 baseline samples > 200 μM (note: 2 of the 3 samples can be collected by home health care personnel)
    AND EITHER
    • Mutation in the arginase I gene
    OR
    • Deficiency in red blood cell (RBC) arginase activity
    3. Has adequate organ function defined as follows:
    • Bone marrow: Hemoglobin ≥10 g/dL; WBC >3.0 × 10^9/L; platelet count ≥ 100,000/μL
    • Hepatic (bilirubin): Total bilirubin ≤ 2.0 × upper limit of normal (ULN)
    • Hepatic (transaminases): EITHER
    • Aspartate aminotransferase (AST) and alanine aminotransferase
    (ALT) ≤ 3.0 × ULN
    OR
    • AST and/or ALT > 3.0 × ULN but both ≤ 5.0 × ULN, and in the opinion of the Investigator, related to Arginase 1 deficiency
    • Renal: serum creatinine < 1.5 × ULN
    4. If female and of child-bearing potential, has a negative serum pregnancy test within 7 days before enrollment
    5. If the patient (male or female) is engaging in sexual activity that could lead to pregnancy, must be surgically sterile, post-menopausal (female), or must agree to use a highly effective method of birth control during the study and for a minimum of 30 days after the last study drug administration. Highly effective methods of contraception include:
    combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; progesterone-only hormonal contraception associated with inhibition of ovulation;
    intrauterine device (IUD); or intrauterine hormone-releasing system (IUS).
    6. Patient or legal guardian is able and willing to provide written informed consent and, where required, assent, and to comply with all requirements of study participation (including all study procedures and continuation of prescribed diet modification) prior to any screening procedures.

    PART 2 INCLUSION CRITERION:
    1. Did not experience any adverse event in Part 1 that, in the opinion of the Investigator in consultation with the Sponsor, would preclude continued study participation and dosing of AEB1102
    E.4Principal exclusion criteria
    A patient is excluded from this study if he/she meets any of the following criteria
    1 Had transfusion of ≥ 2 units of RBCs within the 60 days before enrollment
    2. Currently has an active infection requiring systemic treatment
    3. Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
    4. Had unstable hyperammonemia requiring hospitalization within the 14 days before enrollment
    5. Currently has any comorbid condition or laboratory abnormality that in the opinion of the Investigator might compromise the patient's safety, might interfere with participation in the trial, or might interfere with the interpretation of trial results
    6. Is currently participating in another therapeutic clinical trial
    7. Has received any investigational agent within 30 days of enrollment
    8. Has a history of hypersensitivity to PEG or any other component of the AEB1102 (Co-ArgI-PEG) formulation
    9. If female, is lactating or breastfeeding
    E.5 End points
    E.5.1Primary end point(s)
    Safety and tolerability will be assessed by:
    • Adverse events/serious adverse events
    • Physical examinations
    • Vital signs
    • ECGs
    • Clinical laboratory studies (serum chemistries, hematology, coagulation, urinalysis)
    • Low plasma arginine levels associated with clinically significant symptoms
    • Clinically significant hyperammonemia
    • Immunogenicity assessments (levels of anti-AEB1102 and anti-PEG antibodies)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Part 1
    At screening: PE, Vital signs, Clinical lab studies, ECG, AEs, Arginine, ornithine, Ammonia, ALT & AST
    At Baseline: Tryptase & complement C3, AEs, Arginine, ornithine, Ammonia, ALT & AST
    Wk 1 (Dose 1), 3 (Dose 2*), 5 (Dose 3*), 7 (Dose 4*), 9 (Dose 5-7*) & Follow up (2 wks after last dose) : All parameters
    Wk 2, 4, 6, 8 & 10: Vital signs, AEs, Arginine, ornithine, Ammonia, ALT & AST
    *Doses 2 to 7 only needed if arginine suppression or stopping criteria not met. Procedures would continue on an every 2 week interval. Please refer the protocol for more details.

    Part 2
    Each patient will receive up to 7 weeks (8 doses) of repeat dose therapy, primary end point measures for part 2 are detailed in the protocol CAEB1102-101A (Amend 3.0, May 17, 2018) Page 18, Table 2.
    E.5.2Secondary end point(s)
    Pharmacokinetic analyses
    • T1/2, Tmax, Cmax, AUC0-t, AUC0-∞, CL, and Vss

    Plasma arginine levels
    • Magnitude, onset, and duration of changes to arginine levels after AEB1102 administration

    Plasma guanidino compounds levels
    • Magnitude, onset, and duration of changes to guanidino compounds levels after AEB1102 administration
    E.5.2.1Timepoint(s) of evaluation of this end point
    Part 1

    AEB1102 PK sampling:
    Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and Follow up (2 weeks after last dose)

    Plasma arginine levels and Plasma guanidino compounds levels:
    Plasma Arginine and guanidino compounds samples will be collected at the same time points as AEB1102 PK Samples and in addition, will also be collected at the screening visit, at the baseline visit and one additional point between screening and Visit 1

    Part 2
    AEB1102 PK sampling, Plasma arginine levels and Plasma guanidino compounds levels:
    At Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8/EOT and Follow up (2 weeks after final dose)
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy No
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Safety and tolerability study
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA2
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Portugal
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS (last visit of the last subject)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months2
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 7
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 5
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 2
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 5
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Patient or legal guardian is able & willing to provide written informed consent and where required assent, and to comply with all requirements of study participation, prior to any screening procedures.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state1
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 2
    F.4.2.2In the whole clinical trial 12
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Long-term extension study 102A of dosing AEB1102 for up to 3 years starting after a patient completes study CAEB1102-101A will be planned. Eligibility will be determined after completing study
    CAEB1102-101A. Patients must have tolerated the single and repeat doses of AEB1102 without experiencing any clinically significant event that would preclude continued dosing. Dosing in an individual patient will commence approximately four weeks after the end of participation in Study CAEB1102-101A.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-04-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-07-16
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-02-27
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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