A double-blind, randomized, placebo-controlled study and an open-label long-term extension to assess the efficacy and safety of Elafibranor 80 mg in patients with primary biliary cholangitis and insufficient response or intolerance to ursodeoxycholic acid

Argentina, Belgium, Brazil, Canada, Chile, France, Germany, Italy, South Africa, Spain, Switzerland, Turkey (T�rkiye), United Kingdom, United States (ICTRP)

ID di studio ICTRP
NCT04526665 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
non disponibile

Titolo accademico
A Double-blind, Randomized, Placebo-Controlled Study and Open-label Long Term Extension to Evaluate the Efficacy and Safety of Elafibranor 80 mg in Patients With Primary Biliary Cholangitis With Inadequate Response or Intolerance to Ursodeoxycholic Acid (ICTRP)

Titolo pubblico
Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC) (ICTRP)

Malattie studiate
Primary Biliary Cirrhosis (ICTRP)

Intervento studiato
Drug: Elafibranor 80mgDrug: Placebo (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)

Criteri di inclusione/esclusione
Inclusion Criteria

- Males or females age of 18 to 75 years (inclusive)

- Definite or probable Primary biliary cholangitis (PBC) diagnosis

- Alkaline phosphatase (ALP) = 1.67x upper limit of normal (ULN)

- Total bilirubin (TB) = 2x ULN

- Ursodeoxycholic acid (UDCA) for at least 12 months (stable dose = 3 months) prior to
screening, or unable to tolerate UDCA treatment (no UDCA for = 3 months) prior to
screening (per country standard-of-care dosing)

- Must have PBC Worst Itch Numeric rating scale (NRS) collected prior to randomization

- Females participating in this study must be of non-child bearing potential or must
be using highly efficient contraception for the full duration of the study and for 1
month after the last drug intake

Exclusion Criteria:

- History or presence of other concomitant liver disease

- Clinically significant hepatic decompensation, including patients with complications
of cirrhosis/portal hypertension

- Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's
disease) or which may diminish life expectancy to < 2 years, including known cancers

- Patient has a positive test for HIV Type 1 or 2 at screening, or patient is known to
have tested positive for HIV

- Evidence of any other unstable or untreated clinically significant disease

- History of alcohol abuse

- For female patients: known pregnancy or lactating

- Use of fibrates and glitazones within 2 months prior to screening

- Use of Obeticholic acid (OCA), azathioprine, cyclosporine, methotrexate,
mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids
(parenteral and oral chronic administration only) potentially hepatotoxic drugs

- (including a-methyl-dopa, sodium valproic acid isoniazid, or nitrofurantoin) within
3 months prior to screening

- Use of antibodies or immunotherapy directed against interleukins (ILs) or other
cytokines or chemokines within 12 months prior to screening

- For patients with previous exposure to OCA, OCA should be discontinued 3 months
prior to screening

- Patients who are currently participating in, plan to participate in, or have
participated in an investigational drug study or medical device study containing
active substance within 30 days or five half-lives, whichever is longer, prior to
screening for patients with previous exposure to seladelpar, seladelpar should be
discontinued 3 months prior to screening

- Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) values > 5 x
ULN

- For patients with AT or TB>ULN at SV1, variability of AT or TB > 40% (see section
3.5.1)

- Albumin<3.0 g/dl

- Severely advanced patients according to Rotterdam criteria (TB > ULN and albumin

- INR > 1.3 due to altered hepatic function

- CPK > 2 x ULN

- Screening serum creatinine > 1.5 mg/dl

- Significant renal disease, including nephritic syndrome, chronic kidney disease
(defined as patients with markers of kidney failure damage or eGFR < 60 mL/min/1.73
m^2) calculated by Modification of diet in renal disease (MDRD)

- Platelet count < 150 x 10^3/L

- AFP > 20 ng/mL with 4-phase liver CT or MRI imaging suggesting presence of liver
cancer

- Known hypersensitivity to the investigational product or to any of the formulation
excipients of the elafibranor or placebo tablet Mental instability or incompetence,
such that the validity of informed consent or ability to be compliant with the study
is uncertain (ICTRP)

non disponibile

Endpoint primari e secondari
Percentage of Participants With Response to Treatment Based on Cholestasis Response at Week 52 (ICTRP)

Key Secondary Endpoint: Percentage of Participants With Response to Treatment Based on ALP Normalization at Week 52;Key Secondary Endpoint: Change From Baseline in Pruritus Based on PBC Worst Itch Numeric Rating Scale (NRS) Score in Participants With Baseline PBC Worst Itch NRS Score =4 to Week 52;Key Secondary Endpoint: Change From Baseline in Pruritus Based on PBC Worst Itch NRS Score in Participants With Baseline PBC Worst Itch NRS Score =4 to Week 24;Change From Baseline in ALP at Weeks 4, 13, 26, 39 and 52;Percentage of Participants With ALP Response From Baseline at Week 52;Percentage of Participants With Response to Treatment According to ALP < 1.5x ULN, ALP Decrease From Baseline >= 40% and TB == Lower Limit of Normal [LLN]) (Rotterdam) at Week 52;Percentage of Participants With Response to Treatment According to TB =0.6 x ULN at Week 52;Percentage of Participants With Response to Treatment According to ALP =1.67 x ULN and TB =1 mg/dL (Momah/ Lindor) at Week 52;Percentage of Participants With Response to Treatment According to no Worsening of TB at Week 52;Percentage of Participants With Response to Treatment According to Complete Biochemical Response at Week 52;PBC 5-, 10- and 15-year Risk Scores Based on United Kingdom (UK)-PBC Score at Week 52;Global PBC Study Group (GLOBE) Score at Week 52;Change From Baseline in Hepatobiliary Injury and Liver Function as Assessed by AST, ALT, Gamma-glutamyl Transferase (GGT), 5 Prime Nucleotidase (5'-NT), and Fractionated ALP (Hepatic) (H1 and H2) at Week 52;Change From Baseline in Hepatobiliary Injury and Liver Function as Measured by Total and Conjugated Bilirubin at Week 52;Change From Baseline in Hepatobiliary Injury and Liver Function as Measured by Albumin at Week 52;Change From Baseline in Hepatobiliary Injury and Liver Function as Measured by INR at Week 52;Change From Baseline in Biomarkers of Inflammation as Measured by High-sensitivity C-reactive Protein (hsCRP) at Week 52;Change From Baseline in Biomarkers of Inflammation as Measured by Fibrinogen and Haptoglobin at Week 52;Change From Baseline in Biomarkers of Inflammation as Measured by Tumor Necrosis Factor Alpha at Week 52;Change From Baseline in Immune Response as Measured by Immunoglobulin (Ig)G and IgM at Week 52;Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Enhanced Liver Fibrosis (ELF) and Plasminogen Activator Inhibitor-1 (PAI-1) at Week 52;Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Cytokeratin-18 (CK-18) at Week 52;Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Transforming Growth Factor Beta (TGF-beta) at Week 52;Change From Baseline in Liver Stiffness Measured by Transient Elastography (TE) at Week 52;Change From Baseline in Lipid Parameters at Week 52;Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52;Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52;Change From Baseline at Week 52 in Bile Acids and Biomarkers of Bile Acid Synthesis as Measured by 7 Alpha-hydroxy-4-cholesten-3-one (C4) at Week 52;Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis as Measured Fibroblast Growth Factor 19 at Week 52;Percentage of Participants With Response in PBC Worst Itch NRS Score at Weeks 24 and 52;Percentage of Participants With no Worsening of Pruritus as Measured by the PBC Worst Itch NRS Score at Weeks 24 and 52;Change From Baseline in 5-D Itch at Week 52;Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a at Week 52;Change From Baseline in Epworth Sleepiness Scale (ESS) at Week 52;Change From Baseline in PBC-40 at Week 52;Change From Baseline in Health Utility as Measured by the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) at Week 52;Change From Baseline in T-Scores for Bone Mineral Density Assessed by Dual-energy X-ray Absorptiometry (DEXA) Scanning at Week 52;Change From Baseline in Serum Markers of Bone Turnover Carboxy Terminal Crosslinked Telopeptides of Type 1 Collagen [CTX] at Week 52;Change From Baseline in Serum Markers of Bone Turnover Type 1 Procollagen Peptide [P1NP]) at Week 52;Percentage of Participants With Onset of Clinical Outcomes;Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs);Plasma Concentrations of Elafibranor and GFT1007 (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
non disponibile

Contatti aggiuntivi
Ipsen Medical Director, Ipsen (ICTRP)

ID secondari
2019-004941-34, GFT505B-319-1 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT04526665 (ICTRP)