A Two-part Study to Investigate the Effects in Adults of Two Doses of Golexanolone in Patients With Primary Biliary Cholangitis (PBC) With Fatigue and Cognitive Dysfunction

NCT07304843 | Recruiting Phase 1

• 5 other identifiers: UCAB-CT-052024-515907-20-00IRAS ID 1003871515-04-27580-22-1E-66175679-514.02.02-1264666
• Study Type: interventional
• Target: 84
• Locations: 8 countries
• Sites: 36

Brief Summary

The present phase 1b/2 randomised, double-blind, placebo-controlled, two-part study is designed to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of two dose levels of golexanolone compared with placebo among subjects with a history of non-cirrhotic or Child-Pugh class A cirrhotic Primary Biliary Cholangitis (PBC) with clinically significant fatigue and cognitive symptoms on stable background standard of care (SoC) PBC medication. The objectives of this research study are to assess the safety and tolerability as well the pharmacokinetic (PK) characteristics of golexanolone administered 40 mg BID for 5 days in the target population (part A) and to assess the safety and tolerability, the effects of golexanolone on health-related quality of life (HRQoL), including fatigue, day-time sleepiness and cognitive function as well as Investigator's overall impression of treatment effect of 28 days twice per day (BID) treatment with two dose levels of golexanolone versus placebo (part B).

Conditions

Primary Biliary Cholangitis (PBC)

Keywords

PBC; Cognition; Fatigue

Outcome Measures

Primary Outcomes (2)

• 1. Frequency, intensity, and seriousness of adverse events (AEs) from baseline to Day 28 (part B)

  Frequency, intensity, and seriousness of adverse events (AEs) from baseline to Day 28

  From enrollment to the end of treatment at 28 days

• Frequency, intensity, and seriousness of adverse events (AEs) from baseline to Day 5 (part A)

  Frequency, intensity, and seriousness of adverse events (AEs)

  From Baseline to Day 5

Secondary Outcomes (8)

• 1. Change from baseline to Day 28 in PBC-40 scores for each of the domains (cognition, itch, fatigue, social, emotional, and general symptoms) (part B)

  From baseline to Day 28

• 2. Change from baseline to Day 28 in EQ-5D-3L tool (part B)

  From baseline to Day 28

• 3. Change from baseline to Day 28 in daytime sleepiness related symptoms using the Epworth Sleepiness Scale (ESS) (part B)

  From baseline to Day 28

• 4. Change from baseline to Day 28 in Portosystemic Hepatic Encephalopathy Score (PHES) total score (part B)

  From baseline to Day 28

• 5. Change from baseline to Day 28 in Rey Auditory Verbal Learning test (RAVLT) (part B)

  From baseline to Day 28

Study Arms (5)

Part B: Treatment arm 1 (golexanolone 40 mg)

EXPERIMENTAL

40 mg golexanolone BID

Drug: golexanolone

Part B: Treatment arm 2 (golexanolone 80 mg)

EXPERIMENTAL

80 mg golexanolone BID

Drug: golexanolone

Placebo

PLACEBO COMPARATOR

Part B: Placebo BID

Drug: Placebo

Part A: Golexanolone

EXPERIMENTAL

40 mg golexanolone BID

Drug: golexanolone

Part A: Placebo

PLACEBO COMPARATOR

Placebo BID

Drug: Placebo

Interventions

golexanolone DRUG

soft gelatin capsules, oral dosage twice per day for up to 28 days

Part B: Treatment arm 1 (golexanolone 40 mg)

Placebo DRUG

soft gelatin capsules, oral dosage twice a day for up to 28 days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects age ≥ 18 years
• Diagnosis of PBC based on the presence of ≥2 of 3 key disease characteristics
• Clinically significant fatigue defined for the purposes of this study as a PBC-40 fatigue domain score of ≥29 at screening
• Clinically significant cognitive symptoms, defined for the purposes of this study as a PBC-40 cognitive domain ≥16 at screening
• Stable PBC SoC therapy (if any),for at least 3 months prior to randomisation
• 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
• WOCBP must be willing to use a contraceptive method with a failure rate of \< 1% 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
• Females of non-childbearing potential must have documented tubal ligation or hysterectomy; or be post-menopausal
• 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%
• Willing and able to give informed consent
• The subject should be judged by the Investigator to be lucid and oriented to person, place, time, and situation when giving the informed consent

You may not qualify if:

• Child-Pugh class B or C cirrhosis
• Clinical evidence of hepatic decompensation (e.g. current or prior HE, ascites, or variceal bleeding)
• History of hepatocellular carcinoma
• Bilirubin \>1.5 x ULN
• Glomerular filtration rate (GFR) \<35 mL/min/1.73m2
• Low Haemoglobin (HB), i.e. subjects with moderate/severe anaemia
• Low S-B12 or low P-folate
• Evidence of biliary obstruction
• Any positive result on screening for human immunodeficiency virus (HIV), or hepatitis B (serum hepatitis B surface antigen positive)
• Prolonged QTcF (\>500 ms), or any clinically significant abnormality in the resting ECG, as judged by the Investigator (at screening)
• Concomitant disease characterised by chronic fatigue and/or cognitive impairment
• Clinically significant bowel disease, including obstruction, active inflammatory bowel disease, or malabsorption
• Clinically significant sleep apnoea
• An uncontrolled thyroid disorder
• Subjects with a history of or currently active immune disorders (i.e. uncontrolled) other that PBC (including autoimmune disease) and/or diseases requiring immunosuppressive drugs

Sponsors & Collaborators

• Umecrine Cognition AB: lead

Study Sites (36)

University Hospital Düsseldorf

Düsseldorf, 40225, Germany

RECRUITING

University of Leipzig

Leipzig, 04103, Germany

RECRUITING

Hippokration General Hospital of Athens

Athens, 11527, Greece

RECRUITING

University Hospital of Patras

Pátrai, 26504, Greece

RECRUITING

Bekes County Central Hospital

Gyula, 5700, Hungary

RECRUITING

Facility of CRU Hungary Ltd.

Kistarcsa, 2143, Hungary

RECRUITING

Università di Milano-Bicocca, S.C. ASST Grande Ospedale Metropolitano Niguarda, Dipartimento di Medicina e Chirurgia, Epatologia e Gastroenterologia

Milan, 20162, Italy

NOT YET RECRUITING

Fondazione IRCCS San Gerardo dei Tintori, Autoimmune Liver Disease Centre, ERN-Rare Liver, Department of Medicine and Surgery, Division of Gastroenterology

Monza, 20900, Italy

NOT YET RECRUITING

University of Padova, Department of Surgery, Oncology and Gastroenterology

Padua, 35128, Italy

NOT YET RECRUITING

University Hospital Paolo Giaccone, University of Palermo

Palermo, 90127, Italy

RECRUITING

A. Gemelli Polyclinic, Sacro Cuore Catholic University

Roma, 168, Italy

RECRUITING

Humanitas University

Rozzano, 20089, Italy

RECRUITING

University of Udine

Udine, 33100, Italy

RECRUITING

University Medical Center "Zvezdara"

Belgrade, 11000, Serbia

RECRUITING

Hospital Universitario Parc Taulí

Barcelona, 08208, Spain

RECRUITING

Hospital Clinic Barcelona

Barcelona, 8036, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

RECRUITING

Hospital 12th October, Madrid

Madrid, 28041, Spain

RECRUITING

Hospital Universitario Virgen De La Victoria

Málaga, 29010, Spain

RECRUITING

University Hospital Complex of Pontevedra & IIS Galicia South, Pontevedra

Pontevedra, 36071, Spain

RECRUITING

University Hospital Marquez de Valdecilla, Santander

Santander, 39008, Spain

RECRUITING

Virgen del Rocio University Hospital

Seville, 41013, Spain

RECRUITING

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

NOT YET RECRUITING

Hacettepe University, Fakulty of Medicine, Department of Gastroenterology and Hepatology

Ankara, 06230, Turkey (Türkiye)

RECRUITING

Dicle University Faculty of Medicine Department of Gastroenterology

Diyarbakır, 21280, Turkey (Türkiye)

RECRUITING

Ege University Faculty of Medicine, Department of Gastroenterology

Izmir, 35100, Turkey (Türkiye)

RECRUITING

Kocaeli University Faculty of Medicine Gastroenterology and Hepatology Department

Kocaeli, 41100, Turkey (Türkiye)

RECRUITING

NIHR Birmingham BRC

Birmingham, B15 2TT, United Kingdom

RECRUITING

Glasgow Royal Infirmary

Glasgow, G4 0SF, United Kingdom

RECRUITING

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

RECRUITING

Guy's and St Thomas' Hospital, London

London, SE1 7EH, United Kingdom

RECRUITING

Freeman Hospital

Newcastle, NE7 7DN, United Kingdom

RECRUITING

Nottingham Digestive Diseases Centre and Biomedical Research Centre Nottingham University Hospitals NHS Trust, Queen's Medical Centre

Nottingham, NG7 2UH, United Kingdom

RECRUITING

Oxford University Hospitals NHS Foundation Trust

Oxford, United Kingdom

RECRUITING

Dept of Gastroenterology & Hepatology Portsmouth Hospitals University NHS Trust Queen Alexandra Hospital

Portsmouth, PO6 3LY, United Kingdom

RECRUITING

Royal Wolverhampton NHS Trust, New Cross Hospital

Wolverhampton, WV10 0QP, United Kingdom

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis, Biliary; Fatigue

Interventions

golexanolone

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Pernilla Sandwall

  Umecrine Cognition

  STUDY DIRECTOR

Central Study Contacts

Pernilla Sandwall

CONTACT

+46 70 630 65 19; pernilla.sandwall@umecrine.se

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A (phase 1b) includes 6 subjects on active (40 mg BID for five days) and 2 subjects on placebo (BID for five days) Part B (phase 2a) includes 3 arms (40 mg BID, 80 mg BID or placebo for 28 days)

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: December 26, 2025
• Study Start: April 14, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

HU (2); GR (2); TU (4); SE (1); ES (9); GB (9); IT (7); DE (2)