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

• Sponsor: Abivax S.A. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04023396
• Collaborator: (none)
• Enrollment: 217
• Locations: 120
• Arm: 1
• Anticipated Duration (Months): 37.6
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: ABX464	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 217 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: open-label, follow-up studyopen-label, follow-up study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2b, Open-label, Efficacy and Safety Study of ABX464 as Maintenance Therapy in Patients With Moderate to Severe Ulcerative Colitis
• Actual Study Start Date: Jan 13, 2020
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABX464 50mg All subjects will receive ABX464 administered at 50 mg o.d for an overall period of 96 weeks.	Drug: ABX464; ABX464 All subjects will receive ABX464 administered at 50 mg o.d for an overall period of 96 weeks.

Outcome Measures

Primary Outcome Measures

1. Proportion of patients with clinical remission at week 48 compared to baseline of induction study (ABX464-103) [week 48]

   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

Secondary Outcome Measures

1. Change in Modified Mayo Score and in partial Modified Mayo Score [From baseline to week 96]

   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.

2. Endoscopic changes at week 48 [weeks 48 and 96]

   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.

3. Sustained endoscopic changes at week 48 [weeks 48 and 96]

   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).

4. Glucocorticoid-free clinical remission [From baseline to week 48]

   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.

5. Rectal bleeding [from baseline to week 96]

   Change to baseline in stool and rectal bleeding frequency at every study visit.

6. Fecal calprotectin and C-Reactive Proteine [baseline, week 24, week 48]

   Change to baseline in fecal calprotectin and C-Reactive Proteine levels at week 24, 48, 60, 72, 84 and 96.

7. Clinical response at week 48 [baseline, weeks 48 and 96]

   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.

8. miRNA-124 expression [baseline, week 24 and week 48]

   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.

9. Inflammatory Bowel Disease Questionnaire [baseline, week 24, week 48]

   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.

10. Histopathological evaluation of the effect of ABX464 50 mg on the rectal/sigmoidal infiltrate based on Gebeos score [week 48]

    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).

11. Histopathological evaluation of the effect of ABX464 50 mg on the rectal/sigmoidal infiltrate based on Nancy index scoring system [week 48]

    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.

12. Histopathological evaluation of the effect of ABX464 50 mg on the rectal/sigmoidal infiltrate based on the Robarts Histological index [week 48]

    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.

13. Incidence and description of Adverse Events [From baseline to week 52]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medizinische Universität Innsbruck	Innsbruck		Austria
2	Klinikum Klagenfurt am Wörthersee	Klagenfurt		Austria
3	Ordensklinikum Linz GmbH - Barmherzige Schwestern	Linz		Austria
4	AKH - Medizinische Universität Wien	Vienna		Austria
5	Gomel Regional Clinical Hospital	Gomel		Belarus
6	Minsk city diagnostic center	Minsk		Belarus
7	Regional Clinical Hospital	Minsk		Belarus
8	Vitebsk Regional Clinical Hospital	Vitebsk		Belarus
9	Vitebsk regoinal clinical specialized center	Vitebsk		Belarus
10	AZ Sint-Lucas	Brugge		Belgium
11	C. H. U. St-Pierre	Brussels		Belgium
12	University Hospitals Leuven - campus Gasthuisberg	Leuven		Belgium	3000
13	Brandon Medical Arts Clinic	Brandon		Canada
14	South Edmonton Gastroenterology	Edmonton		Canada
15	LHSC - Victoria Hospital	London		Canada
16	The Ottawa Hospital - General Campus	Ottawa		Canada
17	Mount Sinai Hospital	Toronto		Canada
18	Fakultni nemocnice u sv. Anny v Brne	Brno		Czechia
19	Hepato-Gastroenterologie HK s.r.o.	Hradec Kralove		Czechia
20	MUDr. GREGAR s.r.o.	Olomouc		Czechia
21	Fakultni nemocnice Ostrava	Ostrava-Kunčice		Czechia
22	Nemocnice Na Bulovce	Praha		Czechia
23	Thomayerova nemocnice	Praha		Czechia
24	Nemocnice Slany	Slany		Czechia
25	CHU Amiens - Hopital Sud	Amiens		France
26	CHU Besançon - Hôpital Jean Minjoz	Besançon		France
27	CHU Clermont Ferrand - Hôpital d'Estaing	Clermont-Ferrand		France
28	Hôpital Beaujon	Clichy		France
29	CHU de Grenoble - Hôpital Nord	Grenoble		France
30	Centre Hospitalier Départemental Les Oudairies	La Roche-sur-Yon		France
31	CHU Lille - Hôpital Claude Huriez	Lille		France
32	Hôpital Nord - CHU Marseille	Marseille		France
33	Hopital Saint Eloi	Montpellier		France
34	CHU Nantes - Hôtel Dieu	Nantes		France
35	CHU Nice - Hôpital de l'Archet 2	Nice		France
36	CHU Reims - Hôpital Robert Debré	Reims		France
37	CHU Rennes - Hôpital Pontchaillou	Rennes		France
38	CHU de Rouen - Hôpital Charles Nicolle	Rouen		France
39	CHU Saint Etienne - Hôpital Nord	Saint-Étienne		France
40	CHU Strasbourg - Hôpital Hautepierre	Strasbourg		France
41	Hopital Rangueil	Toulouse		France
42	Hôpital de Brabois Adultes	Vandœuvre-lès-Nancy		France
43	Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin		Germany
44	Florence-Nightingale-Krankenhaus-Diakonie Kaiserswerth	Düsseldorf		Germany
45	Klinikum der Johann Wolfgang Goethe-Universitaet	Frankfurt		Germany
46	Studiengesellschaft BSF Unternehmergesellschaft haftungsbeschraenkt	Halle		Germany
47	Universitaetsklinikum Halle (Saale)	Halle		Germany
48	Medizinische Hochschule Hannover	Hanover		Germany
49	Johanna-Etienne-Krankenhaus	Neuss		Germany
50	Tumorzentrum Nordthueringen MVZ GmbH	Nordhausen		Germany
51	Dr. Tasso Bieler	Riesa		Germany
52	Universitaetsklinikum Ulm	Ulm		Germany
53	DRC Gyogyszervizsgalo Kozpont Kft.	Balatonfured		Hungary
54	Obudai Egeszsegugyi Centrum Kft.	Budapest		Hungary
55	Pannonia Maganorvosi Centrum	Budapest		Hungary
56	Semmelweis Egyetem	Budapest		Hungary
57	Debreceni Egyetem	Debrecen		Hungary
58	Vasutegeszsegugyi Kft. - Debreceni Egeszsegugyi Kozpont	Debrecen		Hungary
59	Petz Aladar Megyei Oktato Korhaz	Győr		Hungary
60	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi	Bologna		Italy
61	Fondazione Poliambulanza Istituto Ospedaliero	Brescia		Italy
62	Azienda Ospedaliero Universitaria Mater Domini	Catanzaro		Italy
63	I.R.C.C.S Policlinico San Donato	Milano		Italy
64	Ospedale Sacro Cuore Don Calabria	Negrar		Italy
65	Azienda Ospedaliera di Padova	Padova		Italy
66	Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone	Palermo		Italy
67	Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello)	Pisa		Italy
68	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma		Italy
69	Istituto Clinico Humanitas	Rozzano		Italy
70	Szpital Uniwersytecki nr 2 im.dr J. Biziela	Bydgoszcz		Poland
71	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland
72	Centrum Medyczne Plejady	Kraków		Poland
73	Santa Familia Centrum Badan, Profilaktyki i Leczenia	Lodz		Poland
74	Wojskowy Szpital Kliniczny w Lublinie	Lublin		Poland
75	Trialmed CRS	Piotrkow Trybunalski		Poland
76	Centrum Medyczne Grunwald	Poznan		Poland
77	KO-MED Centra Kliniczne Pulawy	Pulawy		Poland
78	Gabinet Lekarski Bartosz Korczowski	Rzeszow		Poland
79	Centrum Zdrowia MDM	Warszawa		Poland
80	Nzoz Vivamed	Warszawa		Poland
81	Centrum Zdrowia Tuchow Sp. z o.o.	Wierzchosławice		Poland
82	Centrum Badan Klinicznych Piotr Napora Lekarze Spolka Partnerska	Wroclaw		Poland
83	Centrum Medyczne Oporow	Wroclaw		Poland
84	LexMedica	Wroclaw		Poland
85	Clinical Center " Dr Dragisa Misovic Dedinje"	Belgrad		Serbia
86	Clinical Center Bezanijska Kosa	Belgrad		Serbia
87	General Hospital Uzice	Užice		Serbia
88	Alian s.r.o.	Bardejov		Slovakia
89	Gastromedic, s.r.o.	Nové Zámky		Slovakia
90	Gastro I, s.r.o.	Prešov		Slovakia
91	Endomed, s.r.o.	Vranov Nad Topľou		Slovakia
92	Accout Center s.r.o.	Šahy		Slovakia
93	General Hospital Celje	Celje		Slovenia
94	University Medical Centre Maribor	Maribor		Slovenia
95	General Hospital Murska Sobota	Murska Sobota		Slovenia
96	Centro Médico Teknon	Barcelona		Spain
97	Hospital Universitario Reina Sofia	Córdoba		Spain
98	Hospital Universitario de Gran Canaria Dr. Negrin	Las Palmas De Gran Canaria		Spain
99	Hospital Quironsalud Malaga	Málaga		Spain
100	CNE Cherkasy Regional Hospital of Cherkasy Regional Council	Cherkasy		Ukraine
101	I.I.Mechnykov Dnipropetrovsk Regional Clinical Hospital	Dnipro		Ukraine
102	Central City Clinical Hospital Dept of Theraphy No. 2 SHEI Ivano-Frankivsk NMU	Ivano-Frankivs'k		Ukraine
103	CHI Kharkiv City Clinical Hospital #13	Kharkiv		Ukraine
104	CNE Prof. O.O. Shalimov Kharkiv City Clinical Hospital #2 of KCC	Kharkiv		Ukraine
105	Communal Non-commercial Enterprise of Kharkiv Regional Council Regional Clinical Hospital	Kharkiv		Ukraine
106	CI Kherson CCH	Kherson		Ukraine
107	Khmelnytska Regional Hospital	Khmelnytskyi		Ukraine
108	Communal Institution of Kyiv Regional Council Kyiv Regional Clinical Hospital	Kyiv		Ukraine
109	Lviv Regional Clinical Hospital D.Halytskyi Lviv NMU	Lviv		Ukraine
110	Ternopil University Hospital	Ternopil'		Ukraine
111	CCH #1 Vinnytsia M.I. Pyrogov NMU Ch of Propaedeutics of IM	Vinnytsia		Ukraine
112	M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU	Vinnytsia		Ukraine
113	MCIC MC LLC Health Clinic	Vinnytsia		Ukraine
114	CI City Clinical Hospital #6 Dept of Gastroenterology	Zaporizhzhia		Ukraine
115	CNCE "City Hospital 9" Zaporizhzhia CC	Zaporizhzhia		Ukraine
116	A. Novak Transcarpathian Regional Clinical Hospital	Úzhgorod		Ukraine
117	Fairfield General Hospital	Bury		United Kingdom
118	Guy's Hospital	London		United Kingdom
119	University College London Hospitals	London		United Kingdom
120	Nottingham University Hospitals Queen's Medical Centre	Nottingham		United Kingdom

Sponsors and Collaborators

• Abivax S.A.

Investigators

• Principal Investigator: Severine VERMEIRE, MD, Universitaire Ziekenhuizen Leuven

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abivax S.A.
• ClinicalTrials.gov Identifier: NCT04023396
• Other Study ID Numbers: ABX464-104
• First Posted: Jul 17, 2019
• Last Update Posted: Dec 22, 2021
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Abivax S.A.: moderate to severe ulcerative colitis
• Additional relevant MeSH terms: Colitis; Colitis, Ulcerative; Ulcer

Study Results

No Results Posted as of Dec 22, 2021