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    Summary
    EudraCT Number:2018-003199-10
    Sponsor's Protocol Code Number:OLE-NLRC4/XIAP.2016.001
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:
    Date on which this record was first entered in the EudraCT database:2018-10-04
    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 ConcernedGermany - BfArM
    A.2EudraCT number2018-003199-10
    A.3Full title of the trial
    Open-label extension study with Tadekinig alfa (r-hIL-18BP) to monitor safety and tolerability in patients with IL-18 driven monogenic autoinflammatory conditions: NLRC4 mutation and XIAP deficiency
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    OPEN-LABEL STUDY: THERAPEUTIC USE OF TADEKINIG ALFA IN NLRC4 MUTATION AND XIAP DEFICIENCY
    A.4.1Sponsor's protocol code numberOLE-NLRC4/XIAP.2016.001
    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 SponsorAB2 Bio Ltd.
    B.1.3.4CountrySwitzerland
    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 supportAB2 Bio Ltd.
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAB2 Bio Ltd.
    B.5.2Functional name of contact pointEduardo Schiffrin
    B.5.3 Address:
    B.5.3.1Street Addressinnovation Park Buildling B
    B.5.3.2Town/ cityLausanne
    B.5.3.3Post code1015
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number0041216940043
    B.5.6E-mailEduardo.Schiffrin@ab2bio.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 numberEMA/OD/150/16
    D.3 Description of the IMP
    D.3.1Product nameTadekinig alfa
    D.3.2Product code r-hIL-18BP
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation Yes
    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 INNTadekinig alfa
    D.3.9.1CAS number 220712-29-8
    D.3.9.2Current sponsor coder-hIL-18BPa
    D.3.9.3Other descriptive nameTADEKINIG ALFA
    D.3.9.4EV Substance CodeSUB180338
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number85
    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 injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    NLRC4 mutation
    XIAP deficiency
    E.1.1.1Medical condition in easily understood language
    NLRC4 mutation
    XIAP deficiency
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    This is an open-label extension study for patients previously enrolled in the preceding clinical trial NLRC4/XIAP.2016.001 (IND N° 127953 _ EudraCT number: 2018-003297-27) to evaluate the long-term safety and tolerability of TA in patients suffering from pediatric monogenic autoinflammatory diseases harboring deleterious mutations of NLRC4 and XIAP
    E.2.2Secondary objectives of the trial
    Not applicable
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Patients have participated in the preceding clinical trial NLRC4/XIAP.2016.001 (IND N° 127953 _ EudraCT number: 2018-003297-27) by one of the following mechanisms:
    a. Patients that have completed the first 18-week RCT phase of the preceding clinical trial but were not eligible for the RW phase due to flare symptoms.
    b. Patients that completed the first 18-week RCT phase and completed the RW phase of the preceding clinical trial.
    c. Patients who have exited either the RCT or RW phase of the preceding clinical trial due to treatment failure requiring rescue immunosuppression. Such patients must wait a minimum of 4 weeks after treatment discontinuation from the preceding clinical trial before enrolling in this OLE. If patients do not consent to enroll in the OLE after their early termination in the main study, they will be asked to continue with the planned visits of the main study.
    The time period between participation in the RCT or RW and the OLE study should not exceed 3 months. After this period, patients are no longer eligible for enrollment into the OLE study.
    2. Women of childbearing potential with negative urine pregnancy test (UPT) at all visits (if UPT is positive, a blood test for human chorionic gonadotropin (hCG) is to be performed) and who agree to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment. Birth control methods considered highly effective are: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner or sexual abstinence. In each case of delayed menstrual period (over one month between menstruations, confirmation of absence of pregnancy is strongly recommended. This recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles. A post-study contraception duration of 4 weeks is recommended taking into account the median half-life of Tadekinig alfa of almost 40h and 5 half-lives representing a duration of 200 hours
    E.4Principal exclusion criteria
    1. Patients may not enter the OLE if they voluntarily withdrew from RCT or RW study or if the time period between participation exceeds 3 months
    2. Evidence or history of malignancy
    3. Evidence of invasive or life-threatening infection
    4. History of tuberculosis
    5. Life-threatening bleeding within 2 weeks of screening
    6. Vaccination with a live vaccine within the previous 3 months
    7. Evidence of severe organ compromise including but not limited to:
     Intractable encephalopathy, psychosis, or seizures
     Creatinine of > 2X ULN (patients receiving dialysis are also excluded)
     Albumin < 1.5 g/dL, ALT>10x ULN, or evidence of acute liver failure
     Mechanical ventilation (including invasive and non-invasive forms)
     Heart failure requiring medical support including medications
     Hypotension from any cause requiring the use of vasopressors
    8. Pregnant or breastfeeding females
    9. Inability to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment.
    10. Inability to provide informed consent, and also assent if applicable
    11. Life expectancy less than 4 weeks
    12. Concomitant use of other immunosuppression except NSAIDs, glucocorticoids, cyclosporine, tacrolimus, IL-1 inhibitors (Anakinra, Canakinumab, or Rilonacept)
    13. Hypersensitivity to the active substance or one of the excipients of the investigational product
    E.5 End points
    E.5.1Primary end point(s)
    - Reports of adverse events: The incidence, nature and severity of AEs will be reported. Reports will be produced according to the MedDRA highest hierarchy / System Organ Class, by MedDRA Preferred Term, by relationship to Tadekinig alfa and by Common Terminology Criteria for Adverse Events (CTCAE)/severity.
    - Abnormal physical examination: body temperature, hepatosplenomegaly, and presence of skin rash.
    - Abnormal Laboratory results:
    Including CRP, ferritin, fibrinogen, D-dimer, and any clinically significant abnormal laboratory results. All clinically significant abnormal laboratory results or assessments must be followed until they resolve (return to normal or baseline values) or stabilize, or until they are judged by the Investigator to be no longer clinically significant.
    - Immunogenicity evaluation: Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies
    - Local tolerability at the injection site (evaluated by a standardized assessment)
    E.5.1.1Timepoint(s) of evaluation of this end point
    26 weeks
    E.5.2Secondary end point(s)
    Not applicable
    E.5.2.1Timepoint(s) of evaluation of this end point
    Not applicable
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    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) 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 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.8.2.4Number of treatment arms in the trial1
    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 No
    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
    Germany
    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
    The end of the OLE trial will be defined as the date of the database lock
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    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 months0
    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: 10
    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.1.1.4.1Number of subjects for this age range: 3
    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) No
    F.1.2.1Number of subjects for this age range: 0
    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
    In this case, the informed consent will be signed by the legal gardian
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 2
    F.4.2.2In the whole clinical trial 10
    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)
    None
    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 Decision2019-03-26
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial Status
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