Dose-Ranging Phase 2b Study of ABX464 in Moderate to Severe Ulcerative Colitis
- Conditions
- Ulcerative Colitis
- Interventions
- Drug: PlaceboDrug: ABX464 25mgDrug: ABX464 50mgDrug: ABX464 100mg
- Registration Number
- NCT03760003
- Lead Sponsor
- Abivax S.A.
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 254
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Men or women age 18 - 75 years;
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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.
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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;
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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;
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Patients are able and willing to comply with study visits and procedures as per protocol;
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Patients should understand, sign and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures are performed;
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Patients should be affiliated to a social security regimen (for French sites only);
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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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ABX464 ABX464 100mg ABX464 will be administrated orally (Capsules) and daily for 16 weeks ABX464 ABX464 50mg ABX464 will be administrated orally (Capsules) and daily for 16 weeks Matching Placebo Placebo Matching placebo will be adminstrated orally (Capsules) and daily for 16 weeks ABX464 ABX464 25mg ABX464 will be administrated orally (Capsules) and daily for 16 weeks
- Primary Outcome Measures
Name Time Method Modified Mayo Score Week 8 Reduction from baseline in Modified Mayo Score
- Secondary Outcome Measures
Name Time Method Mucosal healing Week 8 and Week 16 Mucosal healing is defined as both endoscopic remission and histological remission (Geboes score \< 2.0).
Endoscopic Improvement Week 8 and Week 16 Endoscopic improvement is defined as a Mayo endoscopic sub score of ≤1 (excluding friability)
Stool and rectal bleeding frequency Every visit Assessment of Reduction relative to baseline in stool and rectal bleeding frequency
Clinical remission Week 8 and Week 16 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).
Clinical response Week 8 and Week 16 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.
IBDQ Week 8 and Week 16 Scores and changes from baseline i
Partial Modified Mayo Score Every visit Change from baseline
Fecal calprotectin Week 8 and Week 16 Reduction from baseline in fecal calproctectin
C Reactive Protein Week 8 and Week 16 Reduction from baseline in CRP
Modified Mayo Score Week 16 Change from baseline
Inflammatory Infiltrate Week 8 and Week 16 Inflammatory Infiltrate assessment in rectal/colon biopsies
IL-6, TNFα, IL-1b, IL-10 plasma concentrations Every visit Change relative to baseline
Number of clinically-significant laboratory abnormalities Every visit miR-124 expression Week 8 and Week 16 Increase in miR-124 expression in Total Blood and rectal tissue
Incidence of adverse events leading to investigational medicinal product discontinuation Every visit ABX464 and ABX464-N-Glu Every visit (Except D57) Serum concentration
Number and rate of all adverse events, causally-related adverse events, SAE and causally-related SAEs classified by severity Every visit Endoscopy Remission Week 8 and Week 16 Mayo endoscopic sub score of 0
Incidence of treatment-emergent serious adverse event Every visit
Trial Locations
- Locations (130)
Atlanta Center for Gastroenterology, P.C
🇺🇸Decatur, Georgia, United States
UCSD Health System
🇺🇸San Diego, California, United States
Central Texas Clinical Research, LLC
🇺🇸Austin, Texas, United States
Klinikum Klagenfurt am Wörthersee
🇦🇹Klagenfurt, Austria
AKH - Medizinische Universität Wien
🇦🇹Vienna, Austria
Gomel Regional Clinical Hospital
🇧🇾Gomel, Belarus
Regional Clinical Hospital
🇧🇾Minsk, Belarus
C. H. U. St-Pierre
🇧🇪Brussels, Belgium
UZA
🇧🇪Edegem, Belgium
Brandon Medical Arts Clinic
🇨🇦Brandon, Canada
LHSC - Victoria Hospital
🇨🇦London, Canada
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Canada
South Edmonton Gastroenterology
🇨🇦Edmonton, Canada
Mount Sinai Hospital
🇨🇦Toronto, Canada
Allen Whey Khye Lim Professional Corporation
🇨🇦Saskatoon, Canada
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-Kunčice, Czechia
Nemocnice Na Bulovce
🇨🇿Praha, Czechia
Nemocnice Slany
🇨🇿Slany, Czechia
CHU Amiens - Hopital Sud
🇫🇷Amiens, France
Thomayerova nemocnice
🇨🇿Praha, Czechia
CHU Besançon - Hôpital Jean Minjoz
🇫🇷Besançon, France
Hôpital Beaujon
🇫🇷Clichy, France
CHU de Grenoble - Hôpital Nord
🇫🇷Grenoble, France
Centre Hospitalier Départemental Les Oudairies
🇫🇷La Roche-sur-Yon, France
Hôpital Nord - CHU Marseille
🇫🇷Marseille, France
Hopital Saint Eloi
🇫🇷Montpellier, France
CHU Lille - Hôpital Claude Huriez
🇫🇷Lille, France
CHU Nantes - Hôtel Dieu
🇫🇷Nantes, France
CHU Nice - Hôpital de l'Archet 2
🇫🇷Nice, France
CHU Rennes - Hôpital Pontchaillou
🇫🇷Rennes, France
CHU Reims - Hôpital Robert Debré
🇫🇷Reims, France
CHU de Rouen - Hôpital Charles Nicolle
🇫🇷Rouen, France
CHU Saint Etienne - Hôpital Nord
🇫🇷Saint-Étienne, France
Hopital Rangueil
🇫🇷Toulouse, France
CHU Strasbourg - Hôpital Hautepierre
🇫🇷Strasbourg, France
Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
🇩🇪Berlin, Germany
Studiengesellschaft BSF Unternehmergesellschaft haftungsbeschraenkt
🇩🇪Halle, Germany
Florence-Nightingale-Krankenhaus-Diakonie Kaiserswerth
🇩🇪Düsseldorf, Germany
Klinikum der Johann Wolfgang Goethe-Universitaet
🇩🇪Frankfurt, Germany
Universitaetsklinikum Halle (Saale)
🇩🇪Halle, Germany
Medizinische Hochschule Hannover
🇩🇪Hanover, Germany
Johanna-Etienne-Krankenhaus
🇩🇪Neuss, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
Tumorzentrum Nordthueringen MVZ GmbH
🇩🇪Nordhausen, Germany
Dr. Tasso Bieler
🇩🇪Riesa, Germany
DRC Gyogyszervizsgalo Kozpont Kft.
🇭🇺Balatonfured, Hungary
Obudai Egeszsegugyi Centrum Kft.
🇭🇺Budapest, Hungary
Pannonia Maganorvosi Centrum
🇭🇺Budapest, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Petz Aladar Megyei Oktato Korhaz
🇭🇺Győr, Hungary
Debreceni Egyetem
🇭🇺Debrecen, Hungary
Szpital Uniwersytecki nr 2 im.dr J. Biziela
🇵🇱Bydgoszcz, Poland
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
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 Badan Klinicznych Piotr Napora Lekarze Spolka Partnerska
🇵🇱Wroclaw, Poland
Clinical Center Zvezdara
🇷🇸Belgrade, Serbia
Centrum Medyczne Oporow
🇵🇱Wroclaw, Poland
LexMedica
🇵🇱Wroclaw, Poland
Clinical Center " Dr Dragisa Misovic Dedinje"
🇷🇸Belgrad, Serbia
Clinical Center Bezanijska Kosa
🇷🇸Belgrad, Serbia
General Hospital Uzice
🇷🇸Užice, Serbia
Alian s.r.o.
🇸🇰Bardejov, Slovakia
Endomed, s.r.o.
🇸🇰Vranov Nad Topľou, Slovakia
Gastromedic, s.r.o.
🇸🇰Nové Zámky, Slovakia
Accout Center s.r.o.
🇸🇰Šahy, Slovakia
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
General Hospital Murska Sobota
🇸🇮Murska Sobota, Slovenia
Centro Médico Teknon
🇪🇸Barcelona, Spain
Hospital Quironsalud Malaga
🇪🇸Málaga, Spain
Hospital Universitario de Gran Canaria Dr. Negrin
🇪🇸Las Palmas De Gran Canaria, Spain
I.I.Mechnykov Dnipropetrovsk Regional Clinical Hospital
🇺🇦Dnipro, Ukraine
CI Kherson CCH
🇺🇦Kherson, 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
Khmelnytska Regional Hospital
🇺🇦Khmelnytskyi, Ukraine
Ternopil University Hospital
🇺🇦Ternopil', Ukraine
Communal Institution of Kyiv Regional Council Kyiv Regional Clinical Hospital
🇺🇦Kyiv, Ukraine
MCIC MC LLC Health Clinic
🇺🇦Vinnytsia, Ukraine
CI City Clinical Hospital #6 Dept of Gastroenterology
🇺🇦Zaporizhzhia, Ukraine
A. Novak Transcarpathian Regional Clinical Hospital
🇺🇦Úzhgorod, Ukraine
Fairfield General Hospital
🇬🇧Bury, United Kingdom
University College London Hospitals
🇬🇧London, United Kingdom
Nottingham University Hospitals Queen's Medical Centre
🇬🇧Nottingham, United Kingdom
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Austria
Ordensklinikum Linz GmbH - Barmherzige Schwestern
🇦🇹Linz, Austria
Vitebsk Regional Clinical Hospital
🇧🇾Vitebsk, Belarus
Vitebsk regoinal clinical specialized center
🇧🇾Vitebsk, Belarus
Vasutegeszsegugyi Kft. - Debreceni Egeszsegugyi Kozpont
🇭🇺Debrecen, Hungary
CCH #1 Vinnytsia M.I. Pyrogov NMU Ch of Propaedeutics of IM
🇺🇦Vinnytsia, Ukraine
Minsk city diagnostic center
🇧🇾Minsk, Belarus
AZ Sint-Lucas
🇧🇪Brugge, Belgium
Cliniq s.r.o.
🇸🇰Bratislava, Slovakia
Lviv Regional Clinical Hospital D.Halytskyi Lviv NMU
🇺🇦Lviv, Ukraine
UZ Leuven
🇧🇪Leuven, Belgium
Centrum Zdrowia Tuchow Sp. z o.o.
🇵🇱Wierzchosławice, Poland
General Hospital "Djordje Joanovic"
🇷🇸Zrenjanin, Serbia
Gastro I, s.r.o.
🇸🇰Prešov, Slovakia
University Medical Centre Maribor
🇸🇮Maribor, Slovenia
CNE Cherkasy Regional Hospital of Cherkasy Regional Council
🇺🇦Cherkasy, 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
M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU
🇺🇦Vinnytsia, Ukraine
CNCE "City Hospital 9" Zaporizhzhia CC
🇺🇦Zaporizhzhia, Ukraine
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
General Hospital Celje
🇸🇮Celje, Slovenia
CHU Clermont Ferrand - Hôpital d'Estaing
🇫🇷Clermont-Ferrand, France
Hôpital de Brabois Adultes
🇫🇷Vandœuvre-lès-Nancy, France
Southern Star Research Institute, LLC
🇺🇸San Antonio, Texas, United States
Guy's Hospital
🇬🇧London, United Kingdom