Dose-Ranging Phase 2b Study of ABX464 in Moderate to Severe Ulcerative Colitis

NCT ID: NCT03760003

Last Updated: 2025-11-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 355 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-13
• Study Completion Date: 2021-04-16

Brief Summary

Phase 2b study to evaluate the efficacy and the safety of 3 dose-levels of ABX464, administered daily in patients with moderate to severe Ulcerative Colitis.

Detailed Description

This phase 2b study will evaluate the efficacy and the safety of 3 dose-levels of ABX464, administered daily in improving Modified Mayo Score (MMS) in patients with moderate to severe Ulcerative Colitis who have inadequate response, loss of response, or intolerance with at least one of the following agents: immunosuppressant treatment (i.e. azathioprine, 6-mercaptopurine, methotrexate), tumor necrosis factor alpha [TNF-α] inhibitors, vedolizumab, JAK inhibitors and/or corticosteroid treatment .

Eligible patients will be randomized into 4 parallel intervention/treatment groups: 100mg q.d of ABX464, 50mg q.d of ABX464, 25mg q.d of ABX464, or matching placebo and will be treated for 16 weeks.

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ABX464 100 mg

ABX464 100 mg was administered orally (capsules) once daily for 16 weeks

Group Type: EXPERIMENTAL

ABX464 100 mg

Intervention Type: DRUG

ABX464 100 mg (two capsules of ABX464 50 mg) once daily for 16 weeks

ABX464 50 mg

ABX464 50 mg was administered orally (capsules) once daily for 16 weeks

Group Type: EXPERIMENTAL

ABX464 50 mg

Intervention Type: DRUG

ABX464 50 mg (one capsule of ABX464 50 mg + one capsule of placebo) once daily for 16 weeks

ABX464 25 mg

ABX464 25 mg was administered orally (capsules) once daily for 16 weeks

Group Type: EXPERIMENTAL

ABX464 25 mg

Intervention Type: DRUG

ABX464 25 mg (one capsule of ABX464 25 mg + one capsule of placebo) once daily for 16 weeks

Matching Placebo

Matching placebo was administered orally (capsules) once daily for 16 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Two capsules of placebo once daily for 16 weeks

Interventions

ABX464 100 mg

ABX464 100 mg (two capsules of ABX464 50 mg) once daily for 16 weeks

Intervention Type: DRUG

ABX464 50 mg

ABX464 50 mg (one capsule of ABX464 50 mg + one capsule of placebo) once daily for 16 weeks

Intervention Type: DRUG

ABX464 25 mg

ABX464 25 mg (one capsule of ABX464 25 mg + one capsule of placebo) once daily for 16 weeks

Intervention Type: DRUG

Placebo

Two capsules of placebo once daily for 16 weeks

Intervention Type: DRUG

Other Intervention Names

Obefazimod 100 mg; Obefazimod 50 mg; Obefazimod 25 mg; Obefazimod placebo control

Eligibility Criteria

Inclusion Criteria

• Men or women age 18 - 75 years;
• Diagnosis of moderate to severe active UC (including ulcerative proctitis if proximal extension of disease occurs beyond 10 cm) confirmed by endoscopy and histology at least 12 Weeks prior to screening visit. Moderate to severe active UC defined by Modified Mayo Score (MMS) of 5 to 9 inclusive (on a scale of 0-9). Moderate to severe active UC should be confirmed at screening visit with a centrally read endoscopy sub-score of at least 2 (on a scale of 0-3);
• Patients having either a documented inadequate response, no response, a loss of response, or an intolerance (defined as the occurrence of at least one Adverse Reaction leading to treatment discontinuation) to either immunosuppressant treatment (i.e., azathioprine, 6-mercaptopurine, methotrexate), tumor necrosis factor [TNF] inhibitors, vedolizumab, JAK inhibitors and/or corticosteroid treatment. Inadequate response, no response, loss of response is defined as:

i. Active disease or relapse in spite of thiopurines or methotrexate given at an appropriate dose for at least 3 months (i.e. azathioprine 2-2.5 mg/kg/day or mercaptopurine 1-1.5 mg/kg/day in the absence of leukopenia), and/or ii. Active disease despite corticosteroids treatment (prednisolone up to 0.75 mg/kg/day) over a period of 4 Weeks, and/or iii. Active disease or relapse in spite of adequate treatment (as defined in the SmPC) with tumor necrosis factor [TNF] inhibitors or vedolizumab, and/or iv. Active disease or relapse in spite of adequate treatment with JAK inhibitors over a period of at least 6 Weeks.

• Patients receiving oral corticosteroids must have been on a stable dose of prednisone or prednisone equivalent (≤20 mg/day) or on beclomethasone diproprionate (≤5mg/day) or on budesonide MMX (≤9 mg/day) for at least 2 Weeks prior to the screening visit;
• Topical corticosteroids and topical 5-aminosalicylic acid preparations must have been withdrawn at least 2 Weeks prior to the screening visit;
• Patients who are on oral 5-aminosalicylic acid must have been on a stable dose for at least 4 Weeks prior to the screening visit;
• Patients who are receiving immunosuppressants in the form of azathioprine, 6-mercaptopurine, or methotrexate needed to be on a stable dose for at least 4 Weeks prior to screening visit. Patients taking methotrexate also are advised to take folic acid 1 mg/day (or equivalent) supplementation if there is no contraindication;
• Patients on probiotics (e.g., Culturelle® [Lactobacillus GG, i-Health, Inc.], Saccharomyces boulardii) must be on stable doses for at least 2 Weeks prior to the screening visit;
• Patients on antidiarrheals (e.g., loperamide, diphenoxylate with atropine) must be on stable doses for at least 2 Weeks prior to the screening visit;
• Patients who have received tumor necrosis factor [TNF] inhibitors, vedolizumab or other biologics must have discontinued therapy at least 8 Weeks prior to the screening visit due to lack or insufficient efficacy or intolerance;
• Patients previously treated with cyclosporine, tacrolimus or JAK inhibitors must have discontinued therapy at least 4 Weeks prior to the screening visit due to lack or insufficient efficacy or intolerance;
• Patients previously treated with tube feeding, defined formula diets, or parenteral alimentation/nutrition must have discontinued treatment 3 Weeks before the screening visit and must be able to take, orally, appropriate amount of food (calories) and liquids to maintain body weight;
• Patients with surveillance colonoscopy defined as per ECCO guidelines;
• Patients with the following hematological and biochemical laboratory parameters obtained at screening:

i. Hemoglobin > 9.0 g dL-1; ii. Absolute neutrophil count ≥ 750 mm-3; iii. Platelets ≥ 100,000 mm-3; iv. Total serum creatinine ≤ 1.3 x ULN (upper limit of normal); v. Creatinine clearance > 90 mL min-1 by the Cockcroft-Gault equation within 60 days prior to baseline; vi. Total serum bilirubin < 1.5 x ULN; vii. Alkaline phosphatase, AST (SGOT) and ALT (SGPT) < 2 x ULN;

• Patients are able and willing to comply with study visits and procedures as per protocol;
• Patients should understand, sign and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures are performed;
• Patients should be affiliated to a social security regimen (for French sites only);
• Females and males receiving the study treatment (potentially in combination with immunosuppressant) and their partners must agree to use a highly effective contraceptive method during the study and for 6 months after end of study or early termination. Contraception should be in place at least 2 Weeks prior to study participation. Women must be surgically sterile or if of childbearing potential must use a highly effective contraceptive method. Women of childbearing potential (WOCBP) will enter the study after confirmed menstrual period and a negative pregnancy test. Highly effective methods of contraception include true abstinence, intrauterine device (IUD) or hormonal contraception aiming at inhibition of ovulation, intrauterine hormone releasing system, bilateral tubal ligation, vasectomized partner. True abstinence is defined when this is in line with the preferred and usual lifestyle of the patient. In each case of delayed menstrual period (over one month between menstruations) confirmation of absence of pregnancy is required. This recommendation also applies to WOCBP with an infrequent or irregular menstrual cycle. Female and male patients must not be planning pregnancy during the trial and for 6 months post completion of their participation in the trial. In addition, male participants should use condoms and not donate sperm as long as contraception is required.

Exclusion Criteria

• Patients with Crohn's Disease (CD) or presence or history of fistula, indeterminate colitis (IC), infectious/ischemic colitis or microscopic colitis (lymphocytic and collagenous colitis);
• History of toxic megacolon, abdominal abscess, symptomatic colonic stricture or stoma; history or imminent colectomy, colonic malignancy;
• History or current evidence of colonic dysplasia or adenomatous colonic polyps. Patient with severe gastrointestinal complications; e.g., short bowel syndromes, recent or planned bowel surgery, Ileostomy and/or colostomy, recent bowel perforation;
• History of more than one episode of herpes zoster or a history (single episode) of disseminated zoster;
• Patients with active infections at screening such as infected abdominal abscess, Clostridium difficile (stool antigen and toxin required), CMV (positive IgM), TB and recent infectious hospitalization;
• Patients previously treated with ABX464;
• Acute, chronic or history of clinically relevant pulmonary, cardiovascular, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable CNS pathology such as seizure disorder, angina or cardiac arrhythmias, active malignancy or any other clinically significant medical problems as determined by physical examination and/or laboratory screening tests and/or medical history;
• Acute, chronic or history of immunodeficiency or autoimmune disease;
• History of malignancy excluding patients considered cured (5 years disease free survivors);
• Serious illness requiring systemic treatment and/or hospitalization within 3 Weeks prior to baseline;
• Pregnant or breast-feeding women;
• Illicit drug or alcohol abuse or dependence;
• Patients who received live vaccine 30 days or fewer before first dose of study treatment and/or who's planning to receive such a vaccine during the study duration;
• Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer and during the study;
• Any condition, which in the opinion of the investigator, could compromise the patient's safety or adherence to the study protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abivax S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Séverine VERMEIRE, MD

Role: PRINCIPAL_INVESTIGATOR

Universitaire Ziekenhuizen KU Leuven

Locations

UCSD Health System

San Diego, California, United States

Atlanta Center for Gastroenterology, P.C

Decatur, Georgia, United States

Central Texas Clinical Research, LLC

Austin, Texas, United States

Southern Star Research Institute, LLC

San Antonio, Texas, United States

Medizinische Universität Innsbruck

Innsbruck, , Austria

Klinikum Klagenfurt am Wörthersee

Klagenfurt, , Austria

Ordensklinikum Linz GmbH - Barmherzige Schwestern

Linz, , Austria

AKH - Medizinische Universität Wien

Vienna, , Austria

Gomel Regional Clinical Hospital

Homyel, , Belarus

Minsk city diagnostic center

Minsk, , Belarus

Regional Clinical Hospital

Minsk, , Belarus

Vitebsk Regional Clinical Hospital

Vitebsk, , Belarus

Vitebsk regoinal clinical specialized center

Vitebsk, , Belarus

AZ Sint-Lucas

Bruges, , Belgium

C. H. U. St-Pierre

Brussels, , Belgium

UZA

Edegem, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

Brandon Medical Arts Clinic

Brandon, , Canada

South Edmonton Gastroenterology

Edmonton, , Canada

LHSC - Victoria Hospital

London, , Canada

The Ottawa Hospital - General Campus

Ottawa, , Canada

Allen Whey Khye Lim Professional Corporation

Saskatoon, , Canada

Mount Sinai Hospital

Toronto, , Canada

Fakultni nemocnice u sv. Anny v Brne

Brno, , Czechia

Hepato-Gastroenterologie HK s.r.o.

Hradec Králové, , Czechia

MUDr. GREGAR s.r.o.

Olomouc, , Czechia

Fakultni nemocnice Ostrava

Ostrava-Kunčice, , Czechia

Nemocnice Na Bulovce

Prague, , Czechia

Thomayerova nemocnice

Prague, , Czechia

Nemocnice Slany

Slaný, , Czechia

CHU Amiens - Hopital Sud

Amiens, , France

CHU Besançon - Hôpital Jean Minjoz

Besançon, , France

CHU Clermont Ferrand - Hôpital d'Estaing

Clermont-Ferrand, , France

Hôpital Beaujon

Clichy, , France

CHU de Grenoble - Hôpital Nord

Grenoble, , France

Centre Hospitalier Départemental Les Oudairies

La Roche-sur-Yon, , France

CHU Lille - Hôpital Claude Huriez

Lille, , France

Hôpital Nord - CHU Marseille

Marseille, , France

Hopital Saint Eloi

Montpellier, , France

CHU Nantes - Hôtel Dieu

Nantes, , France

CHU Nice - Hôpital de l'Archet 2

Nice, , France

CHU Reims - Hôpital Robert Debré

Reims, , France

CHU Rennes - Hôpital Pontchaillou

Rennes, , France

CHU de Rouen - Hôpital Charles Nicolle

Rouen, , France

CHU Saint Etienne - Hôpital Nord

Saint-Etienne, , France

CHU Strasbourg - Hôpital Hautepierre

Strasbourg, , France

Hopital Rangueil

Toulouse, , France

Hôpital de Brabois Adultes

Vandœuvre-lès-Nancy, , France

Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, , Germany

Florence-Nightingale-Krankenhaus-Diakonie Kaiserswerth

Düsseldorf, , Germany

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt, , Germany

Studiengesellschaft BSF Unternehmergesellschaft haftungsbeschraenkt

Halle, , Germany

Universitaetsklinikum Halle (Saale)

Halle, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Johanna-Etienne-Krankenhaus

Neuss, , Germany

Tumorzentrum Nordthueringen MVZ GmbH

Nordhausen, , Germany

Dr. Tasso Bieler

Riesa, , Germany

Universitaetsklinikum Ulm

Ulm, , Germany

DRC Gyogyszervizsgalo Kozpont Kft.

Balatonfüred, , Hungary

Obudai Egeszsegugyi Centrum Kft.

Budapest, , Hungary

Pannonia Maganorvosi Centrum

Budapest, , Hungary

Semmelweis Egyetem

Budapest, , Hungary

Debreceni Egyetem

Debrecen, , Hungary

Vasutegeszsegugyi Kft. - Debreceni Egeszsegugyi Kozpont

Debrecen, , Hungary

Petz Aladar Megyei Oktato Korhaz

Győr, , Hungary

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

Bologna, , Italy

Fondazione Poliambulanza Istituto Ospedaliero

Brescia, , Italy

Azienda Ospedaliero Universitaria Mater Domini

Catanzaro, , Italy

I.R.C.C.S Policlinico San Donato

Milan, , Italy

Ospedale Sacro Cuore Don Calabria

Negrar, , Italy

Azienda Ospedaliera di Padova

Padua, , Italy

Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone

Palermo, , Italy

Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello)

Pisa, , Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

Szpital Uniwersytecki nr 2 im.dr J. Biziela

Bydgoszcz, , Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Centrum Medyczne Plejady

Krakow, , Poland

Santa Familia Centrum Badan, Profilaktyki i Leczenia

Lodz, , Poland

Wojskowy Szpital Kliniczny w Lublinie

Lublin, , Poland

Trialmed CRS

Piotrkow Trybunalski, , Poland

Centrum Medyczne Grunwald

Poznan, , Poland

KO-MED Centra Kliniczne Pulawy

Puławy, , Poland

Gabinet Lekarski Bartosz Korczowski

Rzeszów, , Poland

Centrum Zdrowia MDM

Warsaw, , Poland

Nzoz Vivamed

Warsaw, , Poland

Centrum Zdrowia Tuchow Sp. z o.o.

Wierzchosławice, , Poland

Centrum Badan Klinicznych Piotr Napora Lekarze Spolka Partnerska

Wroclaw, , Poland

Centrum Medyczne Oporow

Wroclaw, , Poland

LexMedica

Wroclaw, , Poland

Clinical Center " Dr Dragisa Misovic Dedinje"

Belgrade, , Serbia

Clinical Center Bezanijska Kosa

Belgrade, , Serbia

Clinical Center Zvezdara

Belgrade, , Serbia

General Hospital Uzice

Užice, , Serbia

General Hospital "Djordje Joanovic"

Zrenjanin, , Serbia

Alian s.r.o.

Bardejov, , Slovakia

Cliniq s.r.o.

Bratislava, , Slovakia

Gastromedic, s.r.o.

Nové Zámky, , Slovakia

Gastro I, s.r.o.

Prešov, , Slovakia

Accout Center s.r.o.

Šahy, , Slovakia

Endomed, s.r.o.

Vranov nad Topľou, , Slovakia

General Hospital Celje

Celje, , Slovenia

University Medical Centre Maribor

Maribor, , Slovenia

General Hospital Murska Sobota

Murska Sobota, , Slovenia

Centro Médico Teknon

Barcelona, , Spain

Hospital Universitario Reina Sofia

Córdoba, , Spain

Hospital Universitario de Gran Canaria Dr. Negrin

Las Palmas de Gran Canaria, , Spain

Hospital Quironsalud Malaga

Málaga, , Spain

CNE Cherkasy Regional Hospital of Cherkasy Regional Council

Cherkasy, , Ukraine

I.I.Mechnykov Dnipropetrovsk Regional Clinical Hospital

Dnipro, , Ukraine

Central City Clinical Hospital Dept of Theraphy No. 2 SHEI Ivano-Frankivsk NMU

Ivano-Frankivsk, , Ukraine

CHI Kharkiv City Clinical Hospital #13

Kharkiv, , Ukraine

CNE Prof. O.O. Shalimov Kharkiv City Clinical Hospital #2 of KCC

Kharkiv, , Ukraine

Communal Non-commercial Enterprise of Kharkiv Regional Council Regional Clinical Hospital

Kharkiv, , Ukraine

CI Kherson CCH

Kherson, , Ukraine

Khmelnytska Regional Hospital

Khmelnytskyi, , Ukraine

Communal Institution of Kyiv Regional Council Kyiv Regional Clinical Hospital

Kyiv, , Ukraine

Lviv Regional Clinical Hospital D.Halytskyi Lviv NMU

Lviv, , Ukraine

Ternopil University Hospital

Ternopil, , Ukraine

A. Novak Transcarpathian Regional Clinical Hospital

Uzhhorod, , Ukraine

CCH #1 Vinnytsia M.I. Pyrogov NMU Ch of Propaedeutics of IM

Vinnytsia, , Ukraine

M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU

Vinnytsia, , Ukraine

MCIC MC LLC Health Clinic

Vinnytsia, , Ukraine

CI City Clinical Hospital #6 Dept of Gastroenterology

Zaporizhzhia, , Ukraine

CNCE "City Hospital 9" Zaporizhzhia CC

Zaporizhzhia, , Ukraine

Fairfield General Hospital

Bury, , United Kingdom

Guy's Hospital

London, , United Kingdom

University College London Hospitals

London, , United Kingdom

Nottingham University Hospitals Queen's Medical Centre

Nottingham, , United Kingdom

Countries

United States; Austria; Belarus; Belgium; Canada; Czechia; France; Germany; Hungary; Italy; Poland; Serbia; Slovakia; Slovenia; Spain; Ukraine; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ABX464-103

Identifier Type: -

Identifier Source: org_study_id