ELATIVE: Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC)

Sponsor

Genfit (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04526665

Collaborator

(none)

150

Enrollment

115

Locations

Arms

98.2

Anticipated Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main objective of the study is to evaluate the effect of daily oral administration of 80mg elafibranor on cholestasis (impairment of bile formation and/or bile accumulation) in patients with PBC and inadequate response or intolerance to Ursodeoxycholic Acid (UCDA)

Condition or Disease	Intervention/Treatment	Phase
Primary Biliary Cirrhosis	Drug: Elafibranor 80mg Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a double-blind (DB), randomized, placebo-controlled study followed by an open-label long term extension (LTE)This is a double-blind (DB), randomized, placebo-controlled study followed by an open-label long term extension (LTE)

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 24, 2020

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Dec 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Elafibranor 80mg Study subjects will take 1 tablet per day orally before breakfast with a glass of water each morning	Drug: Elafibranor 80mg Elafibranor 80mg for double blind period (52 to 104 weeks). After completion of the double blind period, participants will be offered the opportunity to enter an open label long term extension study for up to 5 years. Participants will continue the elafibranor dose received during the double blind period.
Placebo Comparator: Placebo Study subjects will take 1 tablet per day orally before breakfast with a glass of water each morning	Drug: Placebo Placebo for double blind period (52 to 104 weeks). After completion of the double blind period, participants will be offered the opportunity to enter an open label long term extension study and to switch to elafibranor 80mg for up to 5 years.

Arm

Intervention/Treatment

Experimental: Elafibranor 80mg

Study subjects will take 1 tablet per day orally before breakfast with a glass of water each morning

Drug: Elafibranor 80mg

Elafibranor 80mg for double blind period (52 to 104 weeks). After completion of the double blind period, participants will be offered the opportunity to enter an open label long term extension study for up to 5 years. Participants will continue the elafibranor dose received during the double blind period.

Placebo Comparator: Placebo

Study subjects will take 1 tablet per day orally before breakfast with a glass of water each morning

Drug: Placebo

Placebo for double blind period (52 to 104 weeks). After completion of the double blind period, participants will be offered the opportunity to enter an open label long term extension study and to switch to elafibranor 80mg for up to 5 years.

Outcome Measures

Primary Outcome Measures

Effect of elafibranor (80 mg/day) on cholestasis [From baseline to 52 weeks of treatment]
Response to treatment defined as Alkaline phosphatase (ALP) < 1.67 x Upper Limit Normal (ULN) and Total Bilirubin (TB) ≤ ULN and ALP decrease ≥ 15 percent

Secondary Outcome Measures

Response to treatment based on ALP normalization [At week 52]
Change in pruritis from baseline [Over 52 weeks of treatment]
Based on PBC Worst Itch Numeric Rating Scale (NRS) score measuring itch over the past 24 hours from 0 (no itch) to 10 (worst itch imaginable)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males or females age of 18 to 75 years (inclusive)
Definite or probable PBC diagnosis
ALP ≥ 1.67x upper limit of normal (ULN)
Total bilirubin (TB) ≤ 2x ULN
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)
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 cirrhosis/portal hypertension complications
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 Human Immunodeficiency Virus (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 azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids; potentially hepatotoxic drugs (including α-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 obeticholic acid (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.
Patients with previous exposure to elafibranor
Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 5x ULN
Albumin < 3.0 g/dL
PBC Severely advanced patients according to Rotterdam criteria (TB > ULN and albumin < LLN)
International normalized ratio (INR) > 1.3 due to altered hepatic function
Creatine phosphokinase CPK > 2X ULN
Serum creatinine > 1.5 mg/dL
Significant renal disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Institute for Liver Health	Chandler	Arizona	United States	85224
2	Keck Medical Center of USC	Los Angeles	California	United States	90033
3	Ruane Clinical Research Group Inc.	Los Angeles	California	United States	90036
4	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
5	University of California, Davis Medical Center	Sacramento	California	United States	95817
6	California Pacific Medical Center - Sutter Pacific Medical Foundation	San Francisco	California	United States	94109
7	University of Colorado Denver and Hospital	Aurora	Colorado	United States	840045
8	South Denver Gastroenterology, P.C.	Englewood	Colorado	United States	80113
9	Yale School of Medicine, Digestive Diseases	New Haven	Connecticut	United States	06510
10	Encore Borland-Groover Clinical Research	Jacksonville	Florida	United States	32256
11	Schiff Center for Liver Diseases/University of Miami	Miami	Florida	United States	33136
12	Digestive Healthcare of Georgia	Atlanta	Georgia	United States	30309
13	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
14	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
15	Beth Israel Deaconess Medical Center (BIDMC)	Boston	Massachusetts	United States	02215
16	Henry Ford Health System	Novi	Michigan	United States	48377
17	Saint Louis University	Saint Louis	Missouri	United States	63104
18	UPMC Center for Liver Diseases	New Hyde Park	New York	United States	11042-11114
19	NYU Langone Health / NYU Grossman School of Medicine	New York	New York	United States	10016
20	Columbia University Medical Center - Center for Liver Disease and Transplantation	New York	New York	United States	10032
21	The New York-Presbyterian Hospital, David H. Koch Center	New York	New York	United States	10065
22	Duke University Medical Center	Durham	North Carolina	United States	27710
23	Carolinas Centre for Liver disease/ Atrium Health	Huntersville	North Carolina	United States	28078
24	Consultants for Clinical Research	Cincinnati	Ohio	United States	45249
25	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
26	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210-1240
27	Investigational Drug Service Pharmacy Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
28	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
29	Medical University of South Carolina- College of Medicine	Charleston	South Carolina	United States	29425
30	Vanderbilt Digestive Disease Center	Nashville	Tennessee	United States	37232
31	Texas Clinical Research Institute, LLC	Arlington	Texas	United States	76012
32	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas	United States	75203
33	Liver Center of Texas, PLLC	Dallas	Texas	United States	75234
34	The University of Texas Southwestern Medical Center-IDS Aston Pharmacy	Dallas	Texas	United States	75390-8575
35	Texas Digestive Disease Consultants dba GI Alliance	Fort Worth	Texas	United States	76104
36	Liver Associates of Texas, P.A.	Houston	Texas	United States	77030
37	St. Luke's Health-Baylor St Luke's Medical center - Advanced Liver Therapies Research	Houston	Texas	United States	77030
38	American Research Corporation	San Antonio	Texas	United States	78215
39	Gastro health & Nutrition-Victoria	Victoria	Texas	United States	77904
40	Intermountain Medical Center - Transplant Services	Murray	Utah	United States	84107
41	University of Utah Hospital-Division of Gastroenterology, Hepatology, and Nutrition	Salt Lake City	Utah	United States	84132
42	University of Virginia Medical Center	Charlottesville	Virginia	United States	22908
43	Maryview Hospital Inc, Bon Secours Liver Institute of Hampton Roads	Newport News	Virginia	United States	23602
44	Richmond Community Hospital LLC, Bon Secours Liver Institute of Richmond	Richmond	Virginia	United States	23226
45	Virginia Commonwealth University Clinical Research Services Unit (CRSU)	Richmond	Virginia	United States	23298
46	Liver Institute Northwest	Seattle	Washington	United States	98105
47	Hospital Italiano de Buenos Aires	Caba	Buenos Aires	Argentina	1199
48	Hospital Alemán	Caba	Buenos Aires	Argentina	C1118AAT
49	Hospital Británico de Buenos Aires	Caba	Buenos Aires	Argentina	C1280AEB
50	Hospital Espanol De Mendoza	Godoy Cruz	Mendoza	Argentina	5547
51	Hospital Italiano de La Plata	La Plata	Provincia De Buenos Aires	Argentina	1900
52	Hospital Provincial del Centenario	Rosario	Santa Fe	Argentina	S2002KDS
53	Hôpital Erasme	Brussels		Belgium	1070
54	Antwerp University Hospital	Edegem		Belgium	2650
55	Universitair Ziekenhuis Gent	Gent		Belgium	9000
56	University Hospital Leuven	Leuven		Belgium	3000
57	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90035-903
58	Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo-HCFMUSP	São Paulo	Sao Paulo	Brazil	05403-000
59	University of Calgary Liver Unit - Heritage Medical Research Clinic (HMRC)	Calgary	Alberta	Canada	T2N 4Z6
60	Gordon and Leslie Diamond Health Care Centre, Division of Gastroenterology	Vancouver	British Columbia	Canada	V5Z IM9
61	Shared Health Inc.-Operating as Health Sciences Centre-John Buhler Research Centre	Winnipeg	Manitoba	Canada	R3E 3P4
62	Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)	Montréal		Canada	H2X 0A9
63	Hospital de La Serena	La Serena	Coquimbo	Chile	1700000
64	Centro de Investigaciones Clinicas (CIC)	Viña Del Mar	Region De Valparaiso	Chile	2540364
65	Clínica Universidad de los Andes	Santiago		Chile	7550000
66	Hospital Clínico Universidad de Chile	Santiago		Chile	8320000
67	Centro de Investigacion Clinica Universidad Catolica CICUC	Santiago		Chile	8330034
68	CHU Amiens Picardie	Amiens		France	80054
69	Hôpital Henri Mondor	Créteil		France	94000
70	CHU Grenoble Alpes - Hôpital Albert Michallon	Grenoble		France	38043
71	Centre Hospitalier Régional d'Orléans	Orléans		France	45067
72	Hôpital Saint-Antoine	Paris		France	75012
73	Hôpital Cochin	Paris		France	75014
74	Hôpital Pitié-Salpétrière	Paris		France	75651
75	Hôpital Haut Lévêque	Pessac		France	33604
76	Hôpital Robert Debré - CHU de Reims	Reims		France	51092
77	Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre	Strasbourg		France	67200
78	Gastro - Sudien	Berlin		Germany	10825
79	Charite - Universitätsmedizin Berlin- CVK - Medizinische Klinik	Berlin		Germany	13353
80	Universitätsklinikum Frankfurt	Frankfurt		Germany	60590
81	Medizinische Hochschule Hannover	Hannover		Germany	30625
82	Center for Gastroenterology and Hepatology (GHZ) Kiel	Kiel		Germany	24146
83	EUGASTRO GmbH	Leipzig		Germany	04103
84	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz		Germany	55131
85	Ospedale Civile di Baggiovara-Struttura Complessa di Medicina ad indririzzo Metabolico Nutrizionale	Modena	Località Baggiovara	Italy	41126
86	Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi	Bologna		Italy	40138
87	Azienda Ospedaliera San Paolo, Dipartimento di Scienza della Salute, UO Medicina VI e Pathologia e Gastroenterologia	Milano		Italy	20142
88	ASST Monza - Ospedale San Gerardo, Gastroenterologia	Monza		Italy	20900
89	Azienda Ospedale- Università degli Studi di Padova UOC Gastroenterologia	Padova		Italy	35128
90	Azienda Ospedaliera Universitaria Policlinico P. Giaccone, UOC di Gastroenterologia-Dip.Medicina Interna e Specialistica	Palermo		Italy	90127
91	Tiervlei Trial Centre	Cape Town	Western Cape	South Africa	7530
92	Groote Schuur Hospital, University of Cape Town - Clinical Research Centre	Cape Town	Western Cap	South Africa	7925
93	Mediclinic Constantiaberg, North Suites	Cape Town		South Africa	7800
94	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
95	Hospital Clinic de Barcelona	Barcelona		Spain	08036
96	Hospital General Universitario Gregorio Marañón	Madrid		Spain	28007
97	Hospital Universitario La Paz	Madrid		Spain	28046
98	Hospital Universitario Puerta de Hierro -Madrid	Madrid		Spain	C.P 28222
99	Complexo Hospitalario Universitario de Pontevedra	Pontevedra		Spain	36071
100	Hospital Universitario Donostia	San Sebastián		Spain	20014
101	Hospital Universitario Marqués de Valdecilla	Santander		Spain	39010
102	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
103	Inselspital, Universitätsspital Bern Universitätsklinik für Viszerale chirurgie und Medizin Hepatologie	Bern		Switzerland	3010
104	Fondazione Epatocentro Ticino	Lugano		Switzerland	6900
105	Ege Universitesi Tip Fakultesi Hastanesi	İzmir	Bornova	Turkey	35100
106	Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Gastroentoloji Bilim Dali	Istanbul	Pendik	Turkey	34890
107	Hacette Universitesi Hastenesi IC, Hastaliklari Anabilim Dali, Gastronenteroloji Bilim Dali, Mithapasa Cad. Hacettepe Mah.	Ankara		Turkey	06230
108	The Newcastle upon Tyne Hospitals NHS Foundation Trust-Freeman Hospital	Newcastle-upon-Tyne	Newcastle	United Kingdom	NE7 7DN
109	Belfast Health and Social Care Trust-Royal Victoria Hospital	Belfast		United Kingdom	BT12 6BA
110	Frimley Health NHS Foundation Trust - Frimley Park Hospital	Camberley		United Kingdom	GU16 7UJ
111	Cambridge University Hospitals NHS Foundation Trust - Addenbrookes Hospital	Cambridge		United Kingdom	CB2 0QQ
112	Hull University Teaching Hospitals NHS Trust , Hull Royal Infirmary	Hull		United Kingdom	HU32J
113	King's College Hospital. King's College NHS Foundation Trust	London		United Kingdom	SE5 9RS
114	Nottingham University Hospitals NHS Trust - Queen's Medical Centre (QMC)	Nottingham		United Kingdom	NG72UH
115	Plymouth Hospitals NHS Trust, Derriford Hospital	Plymouth		United Kingdom	PL6 8DH

Sponsors and Collaborators

Genfit

Investigators

Study Director: Carol Addy, MD, MMSc, Genfit

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Genfit

ClinicalTrials.gov Identifier:

NCT04526665

Other Study ID Numbers:

GFT505B-319-1
2019-004941-34

First Posted:

Aug 26, 2020

Last Update Posted:

Apr 7, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Genfit

Primary Biliary Cholangitis

PBC

Elafibranor

Additional relevant MeSH terms:

Cholangitis

Liver Cirrhosis, Biliary

Study Results

No Results Posted as of Apr 7, 2022