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

A Randomized, Double Blind, Placebo Controlled, Parallel Group, Multiple Dose, Induction Study to Evaluate the Safety, Tolerability and Optimal Dose of ABX464 Compared With Placebo 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

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

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: ABX464 25mg; Drug: ABX464 50mg; Drug: ABX464 100mg; Drug: Placebo

Detailed Description

This phase IIb 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: 25mg q.d of ABX464, 50mg q.d of ABX464, 100mg q.d of ABX464, or matching placebo and will be treated for 16 weeks.

• Study Type: Interventional
• Enrollment (Actual): 254
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
    • Medizinische Universität Innsbruck
  • Klagenfurt, Austria
    • Klinikum Klagenfurt am Wörthersee
  • Linz, Austria
    • Ordensklinikum Linz GmbH - Barmherzige Schwestern
  • Vienna, Austria
    • AKH - Medizinische Universität Wien
• Belarus
  • Gomel, Belarus
    • Gomel Regional Clinical Hospital
  • Minsk, Belarus
    • Minsk city diagnostic center
  • Minsk, Belarus
    • Regional Clinical Hospital
  • Vitebsk, Belarus
    • Vitebsk Regional Clinical Hospital
  • Vitebsk, Belarus
    • Vitebsk regoinal clinical specialized center
• Belgium
  • Brugge, Belgium
    • AZ Sint-Lucas
  • Brussels, Belgium
    • C. H. U. St-Pierre
  • Edegem, Belgium
    • UZA
  • Gent, Belgium
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium
    • UZ Leuven
• Canada
  • Brandon, Canada
    • Brandon Medical Arts Clinic
  • Edmonton, Canada
    • South Edmonton Gastroenterology
  • London, Canada
    • LHSC - Victoria Hospital
  • Ottawa, Canada
    • The Ottawa Hospital - General Campus
  • Saskatoon, Canada
    • Allen Whey Khye Lim Professional Corporation
  • Toronto, Canada
    • Mount Sinai Hospital
• Czechia
  • Brno, Czechia
    • Fakultni nemocnice u sv. Anny v Brne
  • Hradec Kralove, Czechia
    • Hepato-Gastroenterologie HK s.r.o.
  • Olomouc, Czechia
    • MUDr. Gregar s.r.o.
  • Ostrava-Kunčice, Czechia
    • Fakultni Nemocnice Ostrava
  • Praha, Czechia
    • Thomayerova nemocnice
  • Praha, Czechia
    • Nemocnice Na Bulovce
  • Slany, Czechia
    • Nemocnice Slany
• France
  • Amiens, France
    • Chu Amiens - Hopital Sud
  • Besançon, France
    • CHU Besançon - Hôpital Jean Minjoz
  • Clermont-Ferrand, France
    • CHU Clermont Ferrand - Hopital d'Estaing
  • Clichy, France
    • Hopital Beaujon
  • Grenoble, France
    • CHU de Grenoble - Hôpital Nord
  • La Roche-sur-Yon, France
    • Centre Hospitalier Départemental Les Oudairies
  • Lille, France
    • CHU Lille - Hôpital Claude Huriez
  • Marseille, France
    • Hôpital Nord - CHU Marseille
  • Montpellier, France
    • Hopital Saint Eloi
  • Nantes, France
    • CHU Nantes - Hôtel Dieu
  • Nice, France
    • CHU Nice - Hôpital de l'Archet 2
  • Reims, France
    • CHU Reims - Hôpital Robert Debré
  • Rennes, France
    • CHU Rennes - Hôpital Pontchaillou
  • Rouen, France
    • CHU de Rouen - Hôpital Charles Nicolle
  • Saint-Étienne, France
    • CHU Saint Etienne - Hôpital Nord
  • Strasbourg, France
    • CHU Strasbourg - Hopital Hautepierre
  • Toulouse, France
    • Hopital Rangueil
  • Vandœuvre-lès-Nancy, France
    • Hôpital de Brabois Adultes
• Germany
  • Berlin, Germany
    • Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
  • Düsseldorf, Germany
    • Florence-Nightingale-Krankenhaus-Diakonie Kaiserswerth
  • Frankfurt, Germany
    • Klinikum der Johann Wolfgang Goethe-Universitaet
  • Halle, Germany
    • Studiengesellschaft BSF Unternehmergesellschaft haftungsbeschraenkt
  • Halle, Germany
    • Universitaetsklinikum Halle (Saale)
  • Hanover, Germany
    • Medizinische Hochschule Hannover
  • Neuss, Germany
    • Johanna-Etienne-Krankenhaus
  • Nordhausen, Germany
    • Tumorzentrum Nordthueringen MVZ GmbH
  • Riesa, Germany
    • Dr. Tasso Bieler
  • Ulm, Germany
    • Universitaetsklinikum Ulm
• Hungary
  • Balatonfured, Hungary
    • DRC Gyogyszervizsgalo Kozpont Kft.
  • Budapest, Hungary
    • Semmelweis Egyetem
  • Budapest, Hungary
    • Óbudai Egészségügyi Centrum Kft.
  • Budapest, Hungary
    • Pannonia Maganorvosi Centrum
  • Debrecen, Hungary
    • Debreceni Egyetem
  • Debrecen, Hungary
    • Vasutegeszsegugyi Kft. - Debreceni Egeszsegugyi Kozpont
  • Győr, Hungary
    • Petz Aladar Megyei Oktato Korhaz
• Italy
  • Bologna, Italy
    • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
  • Brescia, Italy
    • Fondazione Poliambulanza Istituto Ospedaliero
  • Catanzaro, Italy
    • Azienda Ospedaliero Universitaria Mater Domini
  • Milano, Italy
    • I.R.C.C.S Policlinico San Donato
  • Negrar, Italy
    • Ospedale Sacro Cuore Don Calabria
  • Padova, Italy
    • Azienda Ospedaliera di Padova
  • Palermo, Italy
    • Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
  • Pisa, Italy
    • Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello)
  • Roma, Italy
    • Fondazione Policlinico Universitario Agostino Gemelli Irccs
  • Rozzano, Italy
    • Istituto Clinico Humanitas
• Poland
  • Bydgoszcz, Poland
    • Szpital Uniwersytecki nr 2 im.dr J. Biziela
  • Gdansk, Poland
    • Uniwersyteckie Centrum Kliniczne
  • Kraków, Poland
    • Centrum Medyczne Plejady
  • Lodz, Poland
    • Santa Familia Centrum Badan, Profilaktyki I Leczenia
  • Lublin, Poland
    • Wojskowy Szpital Kliniczny w Lublinie
  • Piotrkow Trybunalski, Poland
    • Trialmed CRS
  • Poznan, Poland
    • Centrum Medyczne Grunwald
  • Pulawy, Poland
    • KO-MED Centra Kliniczne Pulawy
  • Rzeszow, Poland
    • Gabinet Lekarski Bartosz Korczowski
  • Warszawa, Poland
    • Centrum Zdrowia MDM
  • Warszawa, Poland
    • NZOZ Vivamed
  • Wierzchosławice, Poland
    • Centrum Zdrowia Tuchow Sp. z o.o.
  • Wroclaw, Poland
    • Lexmedica
  • Wroclaw, Poland
    • Centrum Medyczne Oporow
  • Wroclaw, Poland
    • Centrum Badan Klinicznych Piotr Napora Lekarze Spolka Partnerska
• Serbia
  • Belgrad, Serbia
    • Clinical Center " Dr Dragisa Misovic Dedinje"
  • Belgrad, Serbia
    • Clinical Center Bezanijska Kosa
  • Belgrade, Serbia
    • Clinical Center Zvezdara
  • Užice, Serbia
    • General Hospital Uzice
  • Zrenjanin, Serbia
    • General Hospital "Djordje Joanovic"
• Slovakia
  • Bardejov, Slovakia
    • ALIAN s.r.o.
  • Bratislava, Slovakia
    • Cliniq s.r.o.
  • Nové Zámky, Slovakia
    • GASTROMEDIC, s.r.o.
  • Prešov, Slovakia
    • Gastro I, s.r.o.
  • Vranov Nad Topľou, Slovakia
    • Endomed, s.r.o.
  • Šahy, Slovakia
    • Accout Center s.r.o.
• Slovenia
  • Celje, Slovenia
    • General Hospital Celje
  • Maribor, Slovenia
    • University Medical Centre Maribor
  • Murska Sobota, Slovenia
    • General Hospital Murska Sobota
• Spain
  • Barcelona, Spain
    • Centro Medico Teknon
  • Córdoba, Spain
    • Hospital Universitario Reina Sofia
  • Las Palmas De Gran Canaria, Spain
    • Hospital Universitario de Gran Canaria Dr. Negrin
  • Málaga, Spain
    • Hospital Quironsalud Malaga
• Ukraine
  • Cherkasy, Ukraine
    • CNE Cherkasy Regional Hospital of Cherkasy Regional Council
  • Dnipro, Ukraine
    • I.I.Mechnykov Dnipropetrovsk Regional Clinical Hospital
  • Ivano-Frankivs'k, Ukraine
    • Central City Clinical Hospital Dept of Theraphy No. 2 SHEI Ivano-Frankivsk NMU
  • Kharkiv, 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
  • Kherson, Ukraine
    • CI Kherson CCH
  • Khmelnytskyi, Ukraine
    • Khmelnytska Regional Hospital
  • Kyiv, Ukraine
    • Communal Institution of Kyiv Regional Council Kyiv Regional Clinical Hospital
  • Lviv, Ukraine
    • Lviv Regional Clinical Hospital D.Halytskyi Lviv NMU
  • Ternopil', Ukraine
    • Ternopil University Hospital
  • Vinnytsia, 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
  • Zaporizhzhia, Ukraine
    • CI City Clinical Hospital #6 Dept of Gastroenterology
  • Zaporizhzhia, Ukraine
    • CNCE "City Hospital 9" Zaporizhzhia CC
  • Úzhgorod, Ukraine
    • A. Novak Transcarpathian Regional Clinical Hospital
• United Kingdom
  • Bury, United Kingdom
    • Fairfield General Hospital
  • London, United Kingdom
    • Guy's Hospital
  • London, United Kingdom
    • University College London Hospitals
  • Nottingham, United Kingdom
    • Nottingham University Hospitals Queen's Medical Centre
• United States
  • California
    • San Diego, California, United States, 92103
      • UCSD Health System
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Atlanta Center for Gastroenterology, P.C
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research, LLC
    • San Antonio, Texas, United States, 78212
      • Southern Star Research Institute, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABX464; ABX464 will be administrated orally (Capsules) and daily for 16 weeks	Drug: ABX464 25mg; ABX464 25mg (One capsule of ABX464 25 mg + One capsule of placebo) once daily for 16 weeks; Drug: ABX464 50mg; ABX464 50mg (One capsule of ABX464 50 mg + One capsule of placebo) once daily for 16 weeks; Drug: ABX464 100mg; ABX464 100mg (two capsules of ABX464 50 mg) once daily for 16 weeks
Placebo Comparator: Matching Placebo; Matching placebo will be adminstrated orally (Capsules) and daily for 16 weeks	Drug: Placebo; Two capsules of placebo once daily for 16 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Mayo Score	Reduction from baseline in Modified Mayo Score	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission	Clinical remission, based on the Mayo Scoring system, is defined as stool frequency subscore = 0 or 1 and rectal bleeding subscore = 0 and endoscopy subscore = 0 or 1 (modified to exclude friability).	Week 8 and Week 16
Clinical response	Clinical Response is defined as a reduction in Mayo Score of at least 2 points and greater than or equal to 30 percent from baseline with an accompanying decrease in rectal bleeding sub-score of greater than or equal to 1 point or absolute rectal bleeding sub-score of less than or equal to 1 point.	Week 8 and Week 16
Endoscopic Improvement	Endoscopic improvement is defined as a Mayo endoscopic sub score of ≤1 (excluding friability)	Week 8 and Week 16
Mucosal healing	Mucosal healing is defined as both endoscopic remission and histological remission (Geboes score < 2.0).	Week 8 and Week 16
Stool and rectal bleeding frequency	Assessment of Reduction relative to baseline in stool and rectal bleeding frequency	Every visit
Partial Modified Mayo Score	Change from baseline	Every visit
Modified Mayo Score	Change from baseline	Week 16
Fecal calprotectin	Reduction from baseline in fecal calproctectin	Week 8 and Week 16
C Reactive Protein	Reduction from baseline in CRP	Week 8 and Week 16
miR-124 expression	Increase in miR-124 expression in Total Blood and rectal tissue	Week 8 and Week 16
IBDQ	Scores and changes from baseline i	Week 8 and Week 16
Inflammatory Infiltrate	Inflammatory Infiltrate assessment in rectal/colon biopsies	Week 8 and Week 16
IL-6, TNFα, IL-1b, IL-10 plasma concentrations	Change relative to baseline	Every visit
ABX464 and ABX464-N-Glu	Serum concentration	Every visit (Except D57)
Endoscopy Remission	Mayo endoscopic sub score of 0	Week 8 and Week 16
Number and rate of all adverse events, causally-related adverse events, SAE and causally-related SAEs classified by severity		Every visit
Incidence of treatment-emergent serious adverse event		Every visit
Incidence of adverse events leading to investigational medicinal product discontinuation		Every visit
Number of clinically-significant laboratory abnormalities		Every visit

Collaborators and Investigators

• Sponsor: Abivax S.A.
• Investigators: Principal Investigator: Severine Vermeire, MD, Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2019
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): April 16, 2021

Study Registration Dates

• First Submitted: November 29, 2018
• First Submitted That Met QC Criteria: November 29, 2018
• First Posted (Actual): November 30, 2018

Study Record Updates

• Last Update Posted (Actual): August 2, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Phase 2b; Dose Ranging; ABX464; Refractory patients
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: ABX464-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No