Clinical trial NCT04023396: Efficacy and Safety Study of ABX464 as Maintenance Therapy in Patients With Moderate to Severe Ulcerative Colitis
Official title: A Phase 2b, Open-label, Efficacy and Safety Study of ABX464 as Maintenance Therapy in Patients With Moderate to Severe Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: moderate to severe ulcerative colitis
Lead sponsor: Abivax S.A.
Sponsor class: INDUSTRY
First posted: 2019-07-17
Enrollment: 217
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open-label, follow-up study
Primary purpose: TREATMENT

Brief summary: A phase 2b study to evaluate the long-term efficacy and safety study of ABX464 50mg as maintenance therapy in patients with moderate to severe Ulcerative Colitis.

Detailed description: This study is an open-label study aiming at evaluating the long-term safety and the efficacy profile of ABX464 given once a day (o.d) at 50 mg in subjects who have been previously enrolled in the ABX464-103 clinical study (induction study) and who are willing to continue their treatment. All subjects will receive ABX464 given at 50mg o.d regardless of their previous treatment and dose received in the ABX464-103 study (i.e. ABX464 100mg, ABX464 50mg, ABX464 25mg or Placebo). The enrolment in this follow-up study will be based on the willingness of the subject to carry on his/her participation. Subjects will be treated with ABX464 for an overall period of 48 weeks. Subjects will be followed up on a monthly basis.

Eligibility criteria: Inclusion Criteria:

* Patients must have completed the 16-week induction treatment period (ABX464-103);
* 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 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 (180 days) after end of study or early termination. Contraception should be in place at least 2 weeks prior to screening. Women must be surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy) or in the postmenopausal state (no menses for 12 months without an alternative medical cause) 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 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 patients should use condom during the trial and for 6 months (180 days) post completion of their participation in the study. Male patients must not donate sperm as long as contraception is required.

Criteria that should be met by patients at week 48 to be eligible for 48 additional weeks of study treatment.

* Patients should be in clinical response. Clinical response is defined as: a reduction in Modified Mayo Score ≥ 2 points and ≥ 30 % from baseline (induction) with an accompanying decrease in rectal bleeding sub-score ≥ 1 point or absolute rectal bleeding sub-score ≤ 1 point.
* Patients able and willing to continue the study treatment and who are compliant with study visits and procedures and who signed the update of the written voluntary informed consent.

Exclusion Criteria:

* Patients who had major protocol deviation(s) in the induction study;
* Patients who permanently discontinued study the treatment in induction study (ABX464-103) because of an adverse event (AE) regardless of relatedness to investigational product;
* Patients who have developed any major illness/condition or evidence of an unstable clinical condition (except UC) that, in the investigator's judgment, will substantially increase the risk to the participant if he or she participates in the study;
* Patients with any other severe acute or chronic medical or psychiatric condition or laboratory or electrocardiogram (ECG) abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study;
* Patients who are participating or plan to participate in other investigational studies (other than induction study) during the study.

Primary outcomes:
measure: Proportion of Patients With Clinical Remission at Week 48 Compared to Baseline of Induction Study (ABX464-103)
timeFrame: week 48
Secondary outcomes:
measure: Proportion of Patients With Clinical Response at Weeks 48 and 96 Compared to Baseline of Induction Study
timeFrame: Weeks 48 and 96
measure: Endoscopic Improvement at Weeks 48 and 96
timeFrame: week 48 and week 96
measure: Endoscopic Remission at Weeks 48 and 96
timeFrame: week 48 and week 96
measure: miRNA-124 Expression
timeFrame: baseline, week 24 and week 48
measure: Incidence and Description of Adverse Events
timeFrame: From baseline to week 96
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Klagenfurt
country: Austria
facility: Klinikum Klagenfurt am Wörthersee
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH - Barmherzige Schwestern
city: Vienna
country: Austria
facility: AKH - Medizinische Universität Wien
city: Gomel
country: Belarus
facility: Gomel Regional Clinical Hospital
city: Minsk
country: Belarus
facility: Minsk city diagnostic center
city: Minsk
country: Belarus
facility: Regional Clinical Hospital
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Hospital
city: Vitebsk
country: Belarus
facility: Vitebsk regoinal clinical specialized center
city: Brugge
country: Belgium
facility: AZ Sint-Lucas
city: Brussels
country: Belgium
facility: C. H. U. St-Pierre
city: Leuven
country: Belgium
facility: University Hospitals Leuven - campus Gasthuisberg
city: Brandon
country: Canada
facility: Brandon Medical Arts Clinic
city: Edmonton
country: Canada
facility: South Edmonton Gastroenterology
city: London
country: Canada
facility: LHSC - Victoria Hospital
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
city: Toronto
country: Canada
facility: Mount Sinai Hospital
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Hradec Kralove
country: Czechia
facility: Hepato-Gastroenterologie HK s.r.o.
city: Olomouc
country: Czechia
facility: MUDr. GREGAR s.r.o.
city: Ostrava-Kunčice
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha
country: Czechia
facility: Nemocnice Na Bulovce
city: Praha
country: Czechia
facility: Thomayerova nemocnice
city: Slany
country: Czechia
facility: Nemocnice Slany
city: Amiens
country: France
facility: CHU Amiens - Hopital Sud
city: Besançon
country: France
facility: CHU Besançon - Hôpital Jean Minjoz
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand - Hôpital d'Estaing
city: Clichy
country: France
facility: Hôpital Beaujon
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Nord
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier Départemental Les Oudairies
city: Lille
country: France
facility: CHU Lille - Hôpital Claude Huriez
city: Marseille
country: France
facility: Hôpital Nord - CHU Marseille
city: Montpellier
country: France
facility: Hopital Saint Eloi
city: Nantes
country: France
facility: CHU Nantes - Hôtel Dieu
city: Nice
country: France
facility: CHU Nice - Hôpital de l'Archet 2
city: Reims
country: France
facility: CHU Reims - Hôpital Robert Debré
city: Rennes
country: France
facility: CHU Rennes - Hôpital Pontchaillou
city: Rouen
country: France
facility: CHU de Rouen - Hôpital Charles Nicolle
city: Saint-Étienne
country: France
facility: CHU Saint Etienne - Hôpital Nord
city: Strasbourg
country: France
facility: CHU Strasbourg - Hôpital Hautepierre
city: Toulouse
country: France
facility: Hopital Rangueil
city: Vandœuvre-lès-Nancy
country: France
facility: Hôpital de Brabois Adultes
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Düsseldorf
country: Germany
facility: Florence-Nightingale-Krankenhaus-Diakonie Kaiserswerth
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet
city: Halle
country: Germany
facility: Studiengesellschaft BSF Unternehmergesellschaft haftungsbeschraenkt
city: Halle
country: Germany
facility: Universitaetsklinikum Halle (Saale)
city: Hanover
country: Germany
facility: Medizinische Hochschule Hannover
city: Neuss
country: Germany
facility: Johanna-Etienne-Krankenhaus
city: Nordhausen
country: Germany
facility: Tumorzentrum Nordthueringen MVZ GmbH
city: Riesa
country: Germany
facility: Dr. Tasso Bieler
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Balatonfured
country: Hungary
facility: DRC Gyogyszervizsgalo Kozpont Kft.
city: Budapest
country: Hungary
facility: Obudai Egeszsegugyi Centrum Kft.
city: Budapest
country: Hungary
facility: Pannonia Maganorvosi Centrum
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Debrecen
country: Hungary
facility: Debreceni Egyetem
city: Debrecen
country: Hungary
facility: Vasutegeszsegugyi Kft. - Debreceni Egeszsegugyi Kozpont
city: Győr
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
city: Brescia
country: Italy
facility: Fondazione Poliambulanza Istituto Ospedaliero
city: Catanzaro
country: Italy
facility: Azienda Ospedaliero Universitaria Mater Domini
city: Milano
country: Italy
facility: I.R.C.C.S Policlinico San Donato
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore Don Calabria
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Palermo
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello)
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im.dr J. Biziela
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Kraków
country: Poland
facility: Centrum Medyczne Plejady
city: Lodz
country: Poland
facility: Santa Familia Centrum Badan, Profilaktyki i Leczenia
city: Lublin
country: Poland
facility: Wojskowy Szpital Kliniczny w Lublinie
city: Piotrkow Trybunalski
country: Poland
facility: Trialmed CRS
city: Poznan
country: Poland
facility: Centrum Medyczne Grunwald
city: Pulawy
country: Poland
facility: KO-MED Centra Kliniczne Pulawy
city: Rzeszow
country: Poland
facility: Gabinet Lekarski Bartosz Korczowski
city: Warszawa
country: Poland
facility: Centrum Zdrowia MDM
city: Warszawa
country: Poland
facility: Nzoz Vivamed
city: Wierzchosławice
country: Poland
facility: Centrum Zdrowia Tuchow Sp. z o.o.
city: Wroclaw
country: Poland
facility: Centrum Badan Klinicznych Piotr Napora Lekarze Spolka Partnerska
city: Wroclaw
country: Poland
facility: Centrum Medyczne Oporow
city: Wroclaw
country: Poland
facility: LexMedica
city: Belgrad
country: Serbia
facility: Clinical Center " Dr Dragisa Misovic Dedinje"
city: Belgrad
country: Serbia
facility: Clinical Center Bezanijska Kosa
city: Užice
country: Serbia
facility: General Hospital Uzice
city: Bardejov
country: Slovakia
facility: Alian s.r.o.
city: Nové Zámky
country: Slovakia
facility: Gastromedic, s.r.o.
city: Prešov
country: Slovakia
facility: Gastro I, s.r.o.
city: Vranov Nad Topľou
country: Slovakia
facility: Endomed, s.r.o.
city: Šahy
country: Slovakia
facility: Accout Center s.r.o.
city: Celje
country: Slovenia
facility: General Hospital Celje
city: Maribor
country: Slovenia
facility: University Medical Centre Maribor
city: Murska Sobota
country: Slovenia
facility: General Hospital Murska Sobota
city: Barcelona
country: Spain
facility: Centro Médico Teknon
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Dr. Negrin
city: Málaga
country: Spain
facility: Hospital Quironsalud Malaga
city: Cherkasy
country: Ukraine
facility: CNE Cherkasy Regional Hospital of Cherkasy Regional Council
city: Dnipro
country: Ukraine
facility: I.I.Mechnykov Dnipropetrovsk Regional Clinical Hospital
city: Ivano-Frankivs'k
country: Ukraine
facility: Central City Clinical Hospital Dept of Theraphy No. 2 SHEI Ivano-Frankivsk NMU
city: Kharkiv
country: Ukraine
facility: CHI Kharkiv City Clinical Hospital #13
city: Kharkiv
country: Ukraine
facility: CNE Prof. O.O. Shalimov Kharkiv City Clinical Hospital #2 of KCC
city: Kharkiv
country: Ukraine
facility: Communal Non-commercial Enterprise of Kharkiv Regional Council Regional Clinical Hospital
city: Kherson
country: Ukraine
facility: CI Kherson CCH
city: Khmelnytskyi
country: Ukraine
facility: Khmelnytska Regional Hospital
city: Kyiv
country: Ukraine
facility: Communal Institution of Kyiv Regional Council Kyiv Regional Clinical Hospital
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospital D.Halytskyi Lviv NMU
city: Ternopil'
country: Ukraine
facility: Ternopil University Hospital
city: Vinnytsia
country: Ukraine
facility: CCH #1 Vinnytsia M.I. Pyrogov NMU Ch of Propaedeutics of IM
city: Vinnytsia
country: Ukraine
facility: M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU
city: Vinnytsia
country: Ukraine
facility: MCIC MC LLC Health Clinic
city: Zaporizhzhia
country: Ukraine
facility: CI City Clinical Hospital #6 Dept of Gastroenterology
city: Zaporizhzhia
country: Ukraine
facility: CNCE "City Hospital 9" Zaporizhzhia CC
city: Úzhgorod
country: Ukraine
facility: A. Novak Transcarpathian Regional Clinical Hospital
city: Bury
country: United Kingdom
facility: Fairfield General Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: University College London Hospitals
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals Queen's Medical Centre
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Severine VERMEIRE, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vermeire S, Sands BE, Tilg H, Tulassay Z, Kempinski R, Danese S, Bunganic I, Nitcheu J, Santo J, Scherrer D, Biguenet S, Ehrlich HJ, Steens JM, Gineste P, Sandborn WJ. ABX464 (obefazimod) for moderate-to-severe, active ulcerative colitis: a phase 2b, double-blind, randomised, placebo-controlled induction trial and 48 week, open-label extension. Lancet Gastroenterol Hepatol. 2022 Nov;7(11):1024-1035. doi: 10.1016/S2468-1253(22)00233-3. Epub 2022 Sep 6.