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    The EU Clinical Trials Register currently displays   43800   clinical trials with a EudraCT protocol, of which   7272   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2022-000422-16
    Sponsor's Protocol Code Number:UCAB-CT-05
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-05-24
    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 ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2022-000422-16
    A.3Full title of the trial
    A randomised, double-blind, placebo-controlled, two-part study to evaluate the pharmacokinetics, safety and tolerability, and preliminary efficacy of two dose levels of golexanolone in subjects with primary biliary cholangitis, fatigue, and cognitive dysfunction.
    Randomizált, kettős vak, placebo-kontrollos, kétrészes vizsgálat a golexanolon két dózisszintje farmakokinetikájának, biztonságosságának és tolerálhatóságának értékelésére primer biliáris cholangitisben, kimerültségben és kognitív diszfunkcióban szenvedő betegeknél.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A two-part study to investigate the effects in adults of two doses of a new drug called golexanolone in patients with primary biliary cholangitis with fatigue and cognitive dysfunction
    Kétrészes vizsgálat egy új, golexanolon nevű gyógyszer két dózisa hatásainak vizsgálatára kimerültséggel és kognitív diszfunkcióval járó primer biliáris cholangitisben szenvedő felnőtt betegek körében
    A.4.1Sponsor's protocol code numberUCAB-CT-05
    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 SponsorUmecrine Cognition AB
    B.1.3.4CountrySweden
    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 supportUmecrine Cognition AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUmecrine Cognition AB
    B.5.2Functional name of contact pointMagnus Doverskog
    B.5.3 Address:
    B.5.3.1Street AddressFogdevreten 2
    B.5.3.2Town/ citySolna
    B.5.3.3Post codeS-171 65
    B.5.3.4CountrySweden
    B.5.4Telephone number+4685248 44 84
    B.5.6E-mailmagnus.doverskog@umecrine.se
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameGolexanolone
    D.3.2Product code GR3027
    D.3.4Pharmaceutical form Capsule, soft
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNGOLEXANOLONE
    D.3.9.1CAS number 208922238-18
    D.3.9.2Current sponsor codeGR3027
    D.3.9.4EV Substance CodeSUB198061
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10.0
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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 No
    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 placeboCapsule, soft
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Primary biliary cholangitis (PBC)
    E.1.1.1Medical condition in easily understood language
    Liver disease caused by autoimmune attack on the small to medium bile ducts
    E.1.1.2Therapeutic area Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level SOC
    E.1.2Classification code 10019805
    E.1.2Term Hepatobiliary disorders
    E.1.2System Organ Class 10019805 - Hepatobiliary disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Part A: To assess the safety and tolerability of treatment with 40 mg golexanolone BID for 5 days in non-cirrhotic or Child-Pugh class A cirrhotic PBC subjects with clinically significant fatigue and cognitive symptoms.
    Part B: To assess the safety and tolerability of 28 days BID treatment with two dose levels of golexanolone in non-cirrhotic or Child-Pugh class A PBC subjects with clinically significant fatigue and cognitive symptoms.
    E.2.2Secondary objectives of the trial
    Part A:
    1. To assess the PK characteristics of golexanolone administered 40 mg BID for 5 days in the target population.
    2. To investigate the metabolite profile of golexanolone in human plasma and urine.

    Part B:
    1. To assess effects of golexanolone on health-related quality of life (HRQoL), including fatigue.
    2. To assess effects of golexanolone on day-time sleepiness.
    3. To assess effects of golexanolone on cognitive function.
    4. To evaluate the Investigator’s overall impression of treatment effect.
    5. To assess the exposure of two dose levels of golexanolone in the target population treated for 28 days.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male and female subjects age ≥ 18 and ≤75 years.
    2. Diagnosis of PBC based on the presence of ≥2 of the 3 key disease characteristics:
    a. Anti-mitochondrial antibody or PBC-specific anti-nuclear antibody titre ≥1/40
    b. Elevated alkaline phosphatase (ALP) (> upper limit of normal [ULN] for the relevant laboratory)
    c. Compatible or diagnostic liver biopsy
    3. Clinically significant fatigue defined for the purposes of this study as a PBC-40 fatigue domain score of ≥29 at screening.
    4. Clinically significant cognitive symptoms, defined for the purposes of this study as a PBC-40 cognitive domain ≥16 at screening.
    5. Stable PBC SoC therapy, which may include UDCA, OCA, bezafibrate and/or fenofibrate. for at least 3 months prior to randomisation.
    6. For all women of childbearing potential (WOCBP) a negative pregnancy test at screening and a negative urine dip-stick pregnancy test at baseline, prior to first dose of IMP will be required.
    7. WOCBP must be willing to use a contraceptive method with a failure rate of < 1% (intrauterine device [IUD], intrauterine hormone-releasing system [IUS], bilateral tubal occlusion, vasectomised partner, sexual abstinence), and agree to continue use of this method for the duration of the study and thereafter for 1 month after the last dosing of the IMP. Note that IUS is the only hormonal contraceptive method allowed due to possible interactions with the IMP.
    8. Females of non-childbearing potential must have documented tubal ligation or hysterectomy; or be post-menopausal (defined as 12 months of amenorrhoea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) 25-140 IE/L and oestradiol <200 pmol/L is confirmatory]).
    9. Fertile male subjects must be willing to use condom and assure that their female partner will use contraceptive methods with a failure rate of < 1%1 to prevent pregnancy and drug exposure of a fertile female partner and refrain from donating sperm from the date of dosing until 1 month after dosing of the IMP. Men who are surgically sterile may be included without they/their partner fulfilling the above criteria on birth control.
    10. Willing and able to give informed consent.
    11. The subject should be judged by the Investigator to be lucid and oriented to person, place, time, and situation when giving the informed consent.
    E.4Principal exclusion criteria
    1. Child-Pugh class B or C cirrhosis.
    2. Clinical evidence of hepatic decompensation (e.g. current or prior HE, ascites, or variceal bleeding).
    3. History of hepatocellular carcinoma.
    4. Bilirubin >1.5 x ULN.
    5. Glomerular filtration rate (GFR) <35 ml/min/1.73m2 estimated using the CKD-EPI equation.
    6. Haemoglobin (HB) <110 g/L, i.e. subjects with moderate/severe anaemia.
    7. S-B12 < 125 pmol/L and/or P-folate < 10 nmol/L.
    8. Evidence of biliary obstruction.
    9. Any positive result on screening for human immunodeficiency virus (HIV), hepatitis B (serum hepatitis B surface antigen positive), hepatitis C (e.g. HCV RNA positive).
    10. Prolonged QTcF (>500 ms), cardiac arrhythmia, or any clinically significant abnormality in the resting ECG, as judged by the Investigator (at screening).
    11. Concomitant disease characterised by chronic fatigue and/or cognitive impairment (e.g. Alzheimer’s, Parkinson’s, etc.) which in the judgement of the Investigator would either limit the potential benefit to the subject and/or confound the interpretation of results.
    12. Clinically significant bowel disease, including obstruction, inflammatory bowel disease, or malabsorption.
    13. Clinically significant sleep apnoea, as defined by >5 episodes/hour more than 70% of occasions, despite use of continuous positive airway pressure (CPAP).
    14. An uncontrolled thyroid disorder:
    a. Uncontrolled hyperthyroidism: defined as any history of hyperthyroidism that has either not been treated with either radioactive iodine and/or surgery or that has been treated with radioactive iodine and/or surgery but has required ongoing continuous or intermittent use of thyroid hormone synthesis inhibitors (i.e. methimazole or propylthiouracil) in the 24 weeks before screening.
    b. Uncontrolled hypothyroidism: defined as initiation of thyroid hormone replacement therapy or dose adjustment of replacement therapy in the 12 weeks before screening.
    c. Subjects without a diagnosed thyroid disease should be excluded if thyroid-stimulating hormone (TSH)-value is above ULN, or/and if free triiodothyronine (FT3)- or free thyroxine (FT4)-values are outside normal limits.
    15. Subjects with a history of or currently active immune disorders other that PBC (including autoimmune disease) and/or diseases requiring immunosuppressive drugs (including azathioprine, prednisone, prednisolone, budesonide, cyclosporine, tacrolimus, methotrexate, or mycophenolate mofetil).
    16. Clinical diagnosis of autoimmune hepatitis overlap defined using the Paris overlap criteria (see Appendix 13.2) [30, 31].
    17. Concurrent liver disease of another aetiology.
    18. The presence, as judged by the Investigator, of clinically significant concomitant illness which would jeopardise safe participation in the study and /or the interpretation of study findings, e.g. major psychiatric disorder and major depressive disorder (HADS-D >10) formally diagnosed by a psychiatrist.
    19. Regular use of prescribed or over the counter medications known to cause fatigue or cognitive dysfunction (including, but not limited to, benzodiazepines, opioids other than codeine phosphate, sleeping pills, regular (daily) antihistamine use in the last 4 weeks, anti-psychotic agents, barbiturates, or recreational drug use).
    Confidential 50 (94)
    20. Use of prohibited medications within 14 days prior to randomisation, including medications sensitive to CYP3A4 and/or Pgp inhibition/induction with a narrow therapeutic window, including use of warfarin and warfarin-like anticoagulants (see Section 9.4.8.2).
    21. Anticipated change in PBC medication and/or significant medical or surgical intervention within the duration of the study.
    22. Regular (more than 1 week per month) alcohol consumption in excess of 14 units per week.
    23. Administration of another new chemical entity (defined as a compound that has not been approved for marketing) or has participated in any other clinical study that included drug treatment with the last administration within 3 months prior to administration of IMP in this study.
    24. Females who are pregnant, nursing or actively trying to conceive a child.
    25. Expected inability to swallow the required number of IMP capsules at the applicable dose level.
    26. History of severe allergy/hypersensitivity or on-going allergy/hypersensitivity, as judged by the Investigator. Known allergy or hypersensitivity to drugs with a similar chemical structure or class to golexanolone, i.e. GABAA receptor modulating steroid antagonists (GAMSA). Known allergy of or hypersensitivity to any other component of the investigational drug (i.e. glyceryl mono and dicaprylocaprate).
    27. Investigator considers the subject unlikely to comply with study procedures, restrictions, and requirements.
    E.5 End points
    E.5.1Primary end point(s)
    Part A: Frequency, intensity, and seriousness of adverse events (AEs), changes from baseline to Day 5 in laboratory parameters and clinical safety parameters.
    Part B: Frequency, intensity, and seriousness of AEs, changes from baseline to Day 28 in laboratory parameters and clinical safety parameters.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Part A: from baseline to Day 5
    Part B: from baseline to Day 28
    E.5.2Secondary end point(s)
    Part A:
    1. PK parameters:
    a. after the first dose: Area under the plasma concentration time curve (AUC)0-24h, maximum plasma concentration (Cmax), time to Cmax (Tmax), terminal elimination rate constant (lambdaz), terminal half-life (T1/2), apparent volume of distribution associated with the terminal elimination phase of the plasma curve (Vz/F), total apparent clearance of drug from plasma (Cl/F).
    b. after the last dose: AUC at steady state (AUCss), maximum and minimum concentration at steady state (Cmax, ss and Cmin, ss), Tmax, % fluctuation, lambdaz, T1/2, CL/F, Vz/ F.
    c. accumulation ratio between first and last dose
    2. Metabolite profile in human plasma and urine (to be reported separately).

    Part B:
    1. Change from baseline to Day 28 in the following HRQoL measures:
    − PBC-40 scores for each of the domains (cognition, itch, fatigue, social, emotional, and general symptoms).
    − EQ-5D-3L tool
    2. Change from baseline to Day 28 in daytime sleepiness related symptoms using the Epworth Sleepiness Scale (ESS).
    3. Change from baseline to Day 28 in a battery of cognitive tests, including:
    − Portosystemic Hepatic Encephalopathy Score (PHES) total score
    − Rey Auditory Verbal Learning test (RAVLT)
    − Delis and Kaplan Executive Function System (D-KEFS) Letter and Category fluency subtests
    4. Clinical Global Impression of change, PBC version (CGI-C-PBC).
    5. Lowest plasma concentration before the next dose (Ctrough) will be assessed pre-dose on Days 1, 7, 14 and 28.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Part A: from baseline to Day 5
    Part B: from baseline to Day 28
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    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) 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
    1b/2
    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 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 trial3
    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 concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA18
    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
    Germany
    Italy
    Serbia
    United Kingdom
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days26
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days26
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    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) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 81
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state18
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 55
    F.4.2.2In the whole clinical trial 101
    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)
    This is a phase 1b/2 study with the unregistered product golexanolone and thus there will be no treatment with golexanolone available after end of study participation.
    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 Decision2022-07-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-06-24
    P. End of Trial
    P.End of Trial StatusOngoing
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