Efficacy and Safety Study of ABX464 as Maintenance Therapy in Patients With Moderate to Severe Ulcerative Colitis

Ulcerative Colitis Clinical Trial

Official title:

A Phase 2b, Open-label, Efficacy and Safety Study of ABX464 as Maintenance Therapy in Patients With Moderate to Severe Ulcerative Colitis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04023396
• Other study ID #: ABX464-104
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 13, 2020
• Est. completion date: March 2023

Study information

• Verified date: December 2021
• Source: Abivax S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 217
• Est. completion date: March 2023
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• ABX464
ABX464 All subjects will receive ABX464 administered at 50 mg o.d for an overall period of 96 weeks.

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck	Innsbruck
Austria	Klinikum Klagenfurt am Wörthersee	Klagenfurt
Austria	Ordensklinikum Linz GmbH - Barmherzige Schwestern	Linz
Austria	AKH - Medizinische Universität Wien	Vienna
Belarus	Gomel Regional Clinical Hospital	Gomel
Belarus	Minsk city diagnostic center	Minsk
Belarus	Regional Clinical Hospital	Minsk
Belarus	Vitebsk Regional Clinical Hospital	Vitebsk
Belarus	Vitebsk regoinal clinical specialized center	Vitebsk
Belgium	AZ Sint-Lucas	Brugge
Belgium	C. H. U. St-Pierre	Brussels
Belgium	University Hospitals Leuven - campus Gasthuisberg	Leuven
Canada	Brandon Medical Arts Clinic	Brandon
Canada	South Edmonton Gastroenterology	Edmonton
Canada	LHSC - Victoria Hospital	London
Canada	The Ottawa Hospital - General Campus	Ottawa
Canada	Mount Sinai Hospital	Toronto
Czechia	Fakultni nemocnice u sv. Anny v Brne	Brno
Czechia	Hepato-Gastroenterologie HK s.r.o.	Hradec Kralove
Czechia	MUDr. GREGAR s.r.o.	Olomouc
Czechia	Fakultni nemocnice Ostrava	Ostrava-Kuncice
Czechia	Nemocnice Na Bulovce	Praha
Czechia	Thomayerova nemocnice	Praha
Czechia	Nemocnice Slany	Slany
France	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-Étienne
France	CHU Strasbourg - Hôpital Hautepierre	Strasbourg
France	Hopital Rangueil	Toulouse
France	Hôpital de Brabois Adultes	Vandœuvre-lès-Nancy
Germany	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
Hungary	DRC Gyogyszervizsgalo Kozpont Kft.	Balatonfured
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	Gyor
Italy	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	Milano
Italy	Ospedale Sacro Cuore Don Calabria	Negrar
Italy	Azienda Ospedaliera di Padova	Padova
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
Poland	Szpital Uniwersytecki nr 2 im.dr J. Biziela	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Centrum Medyczne Plejady	Kraków
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	Pulawy
Poland	Gabinet Lekarski Bartosz Korczowski	Rzeszow
Poland	Centrum Zdrowia MDM	Warszawa
Poland	Nzoz Vivamed	Warszawa
Poland	Centrum Zdrowia Tuchow Sp. z o.o.	Wierzchoslawice
Poland	Centrum Badan Klinicznych Piotr Napora Lekarze Spolka Partnerska	Wroclaw
Poland	Centrum Medyczne Oporow	Wroclaw
Poland	LexMedica	Wroclaw
Serbia	Clinical Center " Dr Dragisa Misovic Dedinje"	Belgrad
Serbia	Clinical Center Bezanijska Kosa	Belgrad
Serbia	General Hospital Uzice	Užice
Slovakia	Accout Center s.r.o.	Šahy
Slovakia	Alian s.r.o.	Bardejov
Slovakia	Gastromedic, s.r.o.	Nové Zámky
Slovakia	Gastro I, s.r.o.	Prešov
Slovakia	Endomed, s.r.o.	Vranov Nad Toplou
Slovenia	General Hospital Celje	Celje
Slovenia	University Medical Centre Maribor	Maribor
Slovenia	General Hospital Murska Sobota	Murska Sobota
Spain	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
Ukraine	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-Frankivs'k
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	Úzhgorod
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
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
Abivax S.A.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with clinical remission at week 48 compared to baseline of induction study (ABX464-103)	Clinical remission (based on the Mayo scoring system) is defined as: a rectal bleeding sub-score = 0, and an endoscopy sub-score =1 (excluding friability), and at least 1-point decrease in stool frequency sub-score from baseline to achieve a stool frequency sub-score =1	week 48
Secondary	Change in Modified Mayo Score and in partial Modified Mayo Score	Change in Modified Mayo Score at weeks 48 and 96 and in partial Modified Mayo Score at every study visit among all patients.; Modified Mayo Score evaluates ulcerative colitis stage, based on four parameters: stool frequency, rectal bleeding, endoscopic evaluation and Physician's global assessment. Each parameter of the score ranges from zero (normal or inactive disease) to 3 (severe activity).; Partial Mayo score uses the 3 non-invasive components of the full Mayo Score (stool frequency, rectal bleeding and Physician's global assessment) and excludes the score for the endoscopic findings. Therefore the maximum score is reduced from 12 to 9 points.	From baseline to week 96
Secondary	Endoscopic changes at week 48	Proportion of patients with endoscopic changes by segment at week 48 among all patients.; Endoscopic improvement is defined as a Mayo endoscopic sub score of =1 (excluding friability).; Endoscopic remission is defined as a Mayo endoscopic sub score of 0.	weeks 48 and 96
Secondary	Sustained endoscopic changes at week 48	Proportion of patients with sustained endoscopic changes at week 48 and 96. Sustained endoscopic changes is defined as the number of patients with endoscopic changes at week 48 among patients who had endoscopic changes during the Induction study (at week 8 or week 16 of study ABX464-103).	weeks 48 and 96
Secondary	Glucocorticoid-free clinical remission	Proportion of patients with glucocorticoid-free clinical remission at week 48. Glucocorticoid-free clinical remission is defined as clinical remission in addition to not requiring any treatment with glucocorticoids for at least 8 weeks prior to week 48.	From baseline to week 48
Secondary	Rectal bleeding	Change to baseline in stool and rectal bleeding frequency at every study visit.	from baseline to week 96
Secondary	Fecal calprotectin and C-Reactive Proteine	Change to baseline in fecal calprotectin and C-Reactive Proteine levels at week 24, 48, 60, 72, 84 and 96.	baseline, week 24, week 48
Secondary	Clinical response at week 48	Proportion of patients with clinical response at week 48 and 96. Clinical response is defined as: a reduction in Mayo Score = 3 points and = 30 % from baseline with an accompanying decrease in rectal bleeding sub-score = 1 point or absolute rectal bleeding sub-score = 1 point.	baseline, weeks 48 and 96
Secondary	miRNA-124 expression	Change relative to baseline in miRNA-124 expression in rectal/sigmoidal biopsies at week 48 and in total blood at week 24 and week 48.	baseline, week 24 and week 48
Secondary	Inflammatory Bowel Disease Questionnaire	This questionnaire is a validated and reliable tool to measure health-related quality of life in adult patients with inflammatory bowel disease, ulcerative colitis, or Crohn's disease. It contains 32 questions, which are divided into four health domains: bowel symptoms (10 questions), systemic symptoms (5 questions), emotional function (12 questions), and social function (5 questions). For each question there are graded responses on a 7-point Likert scale, ranging from 1 (representing the "worst" aspect) to 7 (representing the "best" aspect). Thus, the total IBDQ score ranges from 32 to 224, with higher scores reflecting better well-being.; For study purpose, scores and changes in the Inflammatory Bowel Disease Questionnaire domains will be collected and compared from baseline to week 24 and 48.	baseline, week 24, week 48
Secondary	Histopathological evaluation of the effect of ABX464 50 mg on the rectal/sigmoidal infiltrate based on Gebeos score	Week 48 biopsies will be compared to biopsies taken during the induction study (ABX464-103) to assess the disease evolution at a tissue level, based on the Geboes Score.; The scoring system is composed of 6 major grades that assess the structural changes (0), chronic inflammation (1), lamina propria neutrophils (2), neutrophils in the epithelium (3), crypt destruction (4) and erosion and ulcers (5).	week 48
Secondary	Histopathological evaluation of the effect of ABX464 50 mg on the rectal/sigmoidal infiltrate based on Nancy index scoring system	Week 48 biopsies will be compared to biopsies taken during the induction study (ABX464-103) to assess the disease evolution at a tissue level, based on Nancy index scoring system.; It is a 5-level classification from 0 (absence of significant histological disease) to 4 (severely active disease). Classification in each category depends on the presence or absence of ulceration, acute inflammatory cells infiltrate and chronic inflammatory cells infiltrate.	week 48
Secondary	Histopathological evaluation of the effect of ABX464 50 mg on the rectal/sigmoidal infiltrate based on the Robarts Histological index	Week 48 biopsies will be compared to biopsies taken during the induction study (ABX464-103) to assess the disease evolution at a tissue level, based on the Robarts Histological Index.; The score ranges from 0 (no disease activity) to 33 (severe disease activity) is based on evaluation of 4 parameters: chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in the epithelium and erosion and ulceration.	week 48
Secondary	Incidence and description of Adverse Events	Number and rate of all adverse events, causally-related adverse events, all serious adverse events and causally-related serious adverse events classified by severity.; Incidence of treatment-emergent serious adverse events, hospitalizations, total inpatient days.; Incidence of adverse events leading to investigational product discontinuation. Number of clinically significant laboratory abnormalities.	From baseline to week 52