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    Summary
    EudraCT Number:2018-004837-34
    Sponsor's Protocol Code Number:CAEB1102-300A
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2020-07-13
    Trial 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 ConcernedUK - MHRA
    A.2EudraCT number2018-004837-34
    A.3Full title of the trial
    PEACE (Pegzilarginase Effect on Arginase 1 Deficiency Clinical Endpoints): A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of the Efficacy and Safety of Pegzilarginase in Children and Adults with Arginase 1 Deficiency
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A research study in patients with Arginase I Deficiency to investigate the safety of a new drug and its ability to lower arginine levels
    A.4.1Sponsor's protocol code numberCAEB1102-300A
    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 Address805 Las Cimas Parkway Suite 100
    B.5.3.2Town/ cityAustin, Texas
    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 infusion
    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.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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.IMP: 2
    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 IMPSubcutaneous 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.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    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
    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 demonstrate the efficacy of pegzilarginase relative to placebo based on a statistically significant decrease in plasma arginine (Arg) concentrations
    E.2.2Secondary objectives of the trial
    -Demonstrate the efficacy of pegzilarginase (IMP) relative to placebo (Pbo) based on a statistically significantly greater proportion of clinical
    responders
    -Compare the proportions of subjects with response in the individual components of the key secondary endpoint between IMP and Pbo
    -Compare IMP with Pbo with respect to other aspects of mobility
    -Compare IMP with Pbo with respect to adaptive behavior
    -Compare IMP with Pbo with respect to the number of individual components of the key secondary endpoint exhibiting response
    -Compare IMP with Pbo with respect to the proportion of subjects whose endpoint Arg value falls below target guidance of 200 μmol/L
    -Compare IMP with Pbo with respect to the proportions of subjects whose endpoint Arg value falls within the normal range of 40-115μmol/L
    -Compare IMP with Pbo for changes in guanidino compounds
    -Compare pegzilarginase with placebo with respect to objective measures of neurological/neuromotor manifestations
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. The subject and/or parent/guardian provides written informed consent/assent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
    2. A current diagnosis of ARG1-D as documented in medical records, which must include 1 of the following: elevated plasma arginine levels, a mutation analysis that results in s pathogenic variant, or RBC arginase activity. For entry into this study, subjects must also fulfill the following plasma arginine criteria:
    a. The average of all measured values of plasma arginine during the screening period prior to the randomization visit (Visit 1, Study Day 1) is
    ≥ 250 μmol/L.
    b. If a subject is re-screened, the only values that are considered for eligibility assessment are those in the current screening period.
    3. Subjects must be ≥ 2 years of age on the date of informed consent / assent.
    4. The subject must be assessable for clinically meaningful within subject change (clinical response) on at least 1 component of 1 assessment included in the key secondary endpoints. To be considered assessable, the subject must be able to complete the assessment, and must have a Baseline deficit in at least 1 component as defined in the protocol.
    5. Have received documented confirmation from the investigator and/or dietician that the subject can maintain their diet in accordance with dietary information presented in the protocol, ie, can maintain the current level of protein consumption, including natural protein and essential amino acid supplementation.
    6. Subjects receiving ammonia scavenger therapy, anti-epileptic drugs, and/or medications for spasticity (eg, baclofen) must be on a stable dose of the medication for at least 4 weeks prior to randomization and be willing to remain on a stable dose during the double-blind portion and blinded follow-up portions of the study.
    7. Female and male subjects may participate. Female subjects of childbearing potential must have a negative serum pregnancy test during the screening period before receiving the first dose of study treatment, and a negative urine pregnancy test on the day of the first dose, prior to the first dose. If the subject (male or female) is engaging in sexual activity that could lead to pregnancy, must be surgically sterile, postmenopausal (no menses for 12 months without an alternative medical cause or a high FSH level in the postmenopausal range in women not using hormonal contraception or hormonal replacement therapy), 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); intrauterine hormone-releasing system (IUS); or abstinence (refraining from heterosexual intercourse during the entire period of risk associated with study treatment).
    E.4Principal exclusion criteria
    1. Hyperammonemic episode (defined as an event in which a subject has an ammonia level ≥100 μM with one or more symptoms related to hyperammonemia requiring hospitalization or emergency room management) within the 6 weeks before the first dose of study drug is administered.
    2. Active infection requiring anti-infective therapy within 3 weeks prior to first dose.
    3. Known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
    4. Extreme mobility deficit, defined as either the inability to be assessed on the GFAQ or a score of 1 on the GFAQ.
    5. Other medical conditions or comorbidities that, in the opinion of the investigator would interfere with study compliance or data interpretation (eg, severe intellectual disability precluding required study assessments).
    6. Has participated in a previous interventional study with pegzilarginase.
    7. Has a history of hypersensitivity to polyethylene glycol (PEG) that, in the judgment of the investigator, puts the subject at unacceptable risk for adverse events.
    8. Subject is being treated with botulinum-toxin containing regimens or plans to initiate such regimens during the double-blind or blinded followup portions of the study or received surgical or botulinum-toxin treatment for spasticity-related complications within the 16 weeks prior to the first dose of study treatment in this study.
    9. Is currently participating in another therapeutic clinical trial or has received any investigational agent within 30 days (or 5 half-lives whichever is longer) prior to the first dose of study treatment in this study.
    10. Previous liver or hematopoietic transplant procedure.
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline in plasma arginine after 24 weeks of study treatment
    E.5.1.1Timepoint(s) of evaluation of this end point
    After 24 weeks of study treatment
    E.5.2Secondary end point(s)
    1) Clinical response is defined as a subject exhibiting a response in 2MWT, GMFM-D, or GMFM-E as defined in the protocol.
    2)Response for each component is defined in the protocol.
    3)Response for FMS and GFAQ is defined as a 1-level change at any distance and a 2-level change at any distance, respectively
    4)Response for Vineland Adaptive Behavior Scales (VABS)-II is defined as an improvement by 7.5 points
    5)For each subject, the endpoint is the number of components with response (0, 1, 2, 3, …)
    6)A subject is considered a responder if their endpoint arginine value is <200 μmol/L, and a non-responder otherwise.
    7)A subject is considered a responder if their endpoint arginine value is ≤115 μmol/L, and a non-responder otherwise.
    8)Change from Baseline in guanidino compounds after 24 weeks of study treatment
    9)Neurological manifestations, using functional and spasticity measurements by Modified Ashworth Scale (MAS)
    10)Adverse events (AEs) and anti-drug antibodies (ADAs) will be collected.
    11)PK data will be collected for use in a population PK model.
    E.5.2.1Timepoint(s) of evaluation of this end point
    After 24 weeks of study treatment.
    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 Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA16
    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
    Austria
    Canada
    France
    Germany
    Italy
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    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
    Last visit last subject.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days18
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months3
    E.8.9.2In all countries concerned by the trial days1
    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: 30
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 15
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 15
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 10
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    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 state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 20
    F.4.2.2In the whole clinical trial 40
    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)
    Post the trial, the IMP will continue to be made available to the patient under approved local law until the marketing authorisation.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-06-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-06-10
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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