Clinical trial NCT06456593: Efficacy and Safety of Obefazimod in Subjects With Moderately to Severely Active Crohn's Disease
Official title: A Phase 2b, Multicenter, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Obefazimod in Subjects With Moderately to Severely Active Crohn's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Moderately to Severely Active Crohn Disease
Keywords: Crohn Disease
Lead sponsor: Abivax S.A.
Sponsor class: INDUSTRY
First posted: 2024-06-13
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study has 3 treatment phases, a 12-Week Induction Phase, a 40-Week Maintenance Phase, and a 48-Week Extension Phase.

The objective is to evaluate the efficacy and safety of obefazimod compared to placebo as induction and maintenance therapy in subjects with moderately to severely active CD after inadequate response (no response, loss of response, or intolerance) to conventional therapies and/or advanced therapies.

The primary objective for the 48-Week Extension Phase is to evaluate the safety and tolerability of obefazimod compared with placebo in subjects who are enrolled in the Extension Phase.


Eligibility criteria: Inclusion Criteria:

1. Male or female (at birth) 18 to 75 years old and able to understand, sign, and date the written voluntary informed consent at the visit prior to any protocol-specified procedures
2. Able and willing to comply with study visits and procedures as per protocol.
3. Confirmed and documented diagnosis of CD based on endoscopy and histology reports.
4. Moderately to severely active CD as defined by 220 ≤ CDAI ≤ 450 and SES-CD ≥ 6 for ileo-colonic or colonic disease or SES-CD ≥ 4 for isolated ileal disease (per central reading).
5. Documented inadequate response (defined as lack of response or loss of response or intolerance) to at least one of the following treatments: corticosteroids (CS), immunosuppressants (IS), biologic or biosimilar therapies, or janus kinase (JAK) (note: failure to only 5-aminosalicylic acid \[5-ASA\] is not accepted)
6. Women of childbearing potential (WOCBP) and male subjects with WOCBP partner must agree to comply with contraception requirements as stated in section 4.5 (contraception) of this protocol.
7. Subject should be affiliated to a health insurance policy whenever required by a participating country or state.
8. Subject is able and willing to comply with usual public recommendations for sun protection.

Exclusion Criteria:

Subjects who meet any of the following exclusion criteria will be excluded from the study:

1. WOCBP subject who is pregnant or breast-feeding at screening, or intends to become pregnant during the study; or male subject with WOCBP partner who intends to be pregnant during the study.
2. Current diagnosis of ulcerative colitis (UC) or indeterminate colitis
3. CD without ileal and/or colonic involvement
4. Untreated active external or perianal fistula or abscess. Stable fistula without abscess and with minimal or low drainage may be enrolled. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks before screening colonoscopy or 8 weeks before screening colonoscopy for intra-abdominal abscesses, if no additional surgery is anticipated.
5. Symptomatic bowel stricture and/or stenosis not passable in endoscopy
6. Related to CD surgery:

   1. Current stoma or ileoanal pouch
   2. More than 2 missing complete segments of the following 5 segments: terminal ileum, right colon, transverse colon, left colon, and sigmoid and rectum
   3. Combined previous small bowel resections \> 100 cm
   4. Surgical bowel resection within the past 3 months prior to baseline
   5. Any other manifestation that might require surgery while enrolled in the study
7. Related to CD treatments:

   1. Subject who is currently treated with prohibited concomitant therapies for CD as described in the study protocol
   2. Subject who has previously received natalizumab (or any other α4β1 integrin agonist)
   3. Subject who has failed more than three advanced therapies for the treatment of CD, or two different mechanisms of action for advanced therapies of CD
8. History of, or active, malignancy including nonmelanoma skin cancer (subjects with a 5-year disease-free survival are eligible)
9. History of colonic cancer or colonic low grade or high grade dysplasia adenomatous polyps, and/or at the screening endoscopy, evidence of low grade or high grade dysplasia adenomatous polyps (fully removed or not)
10. Subject with history of, or diagnosed with, the following during screening: primary sclerosing cholangitis, autoimmune hepatitis, or primary biliary cirrhosis
11. Serious illness requiring hospitalization (not related to CD) within 4 weeks prior to screening
12. Subject with the following infectious conditions:

    1. Chronic or recurrent Grade 3 or Grade 4 infection within the last 2 months prior to screening or history of opportunistic infection while not on immunosuppressive therapy
    2. Herpes zoster reactivation within the last 2 months prior to screening
    3. Active infection at screening or any major episode of infection that required hospitalization or treatment with IV antibiotics within 1 month of screening or during screening (fungal infection of nail beds is allowed)
    4. Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) that required treatment per local medical practice or positive test for Clostridioides difficile (C. difficile) toxin at screening.
    5. Subject with human immunodeficiency virus (HIV) infection
    6. Acute or chronic hepatitis B infection at screening (positive for hepatitis B surface antigen \[HbsAg\] or negative for HbsAg and positive for anti-hepatitis B core antibody in conjunction with detectable hepatitis B virus \[HBV\] deoxyribonucleic acid \[DNA\], or detectable HBV DNA).
    7. Acute or chronic hepatitis C virus (HCV) infection as defined by positive for hepatitis C antibody (subjects successfully treated and without recurrence ≥ 1 year with no detectable HCV RNA \[assessed centrally\] are eligible)
    8. Active tuberculosis (TB) or untreated latent TB (For subjects with positive or intermediate QuantiFERON test)
13. Subject with uncontrolled ischemic heart disease and/or a history of congestive heart failure
14. Subject with a known family or personal history of congenital or acquired long QT syndrome, or subjects with a marked baseline prolongation of QT/ heart rate-corrected QT (QTc) interval
15. Subject with a history of torsade de pointe (TdP)
16. Acute or chronic clinically relevant pulmonary, hepatic, or renal functional abnormality, encephalopathy, neuropathy or unstable central nervous system pathology such as seizure disorder, or any other clinically significant medical problems.
17. Subjects who received live vaccine within 3 months prior to screening and/or subject who is planning to receive such a vaccine during the study duration
18. Acute or chronic pancreatitis
19. Subject with the following hematological and biochemical laboratory parameters obtained during the screening period:

    1. Hemoglobin ≤ 8.0 g/dL1
    2. Absolute neutrophil count \< 750/mm3
    3. Platelets \< 100,000 /mm3
    4. eGFR \< 60 mL/min/1.73 m2
    5. Total serum bilirubin \> 1.5 x ULN (except if related to pre-existing and documented Gilbert syndrome)
    6. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 2 x ULN
20. Subject who does not meet the washout period requirements prior to the screening endoscopy as described in the prohibited medication section of the study protocol
21. Use of any investigational or nonregistered product within 3 months or within 5 halflives preceding baseline, whichever is longer, and during the study.
22. Subjects previously treated with obefazimod or with a known hypersensitivity to the active substance or to any of the excipients
23. Illicit drug or alcohol abuse or dependence
24. Subject who is committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
25. Any condition, which in the opinion of the investigator, could compromise the subject's safety or adherence to the study protocol

Primary outcomes:
measure: Induction and maintenance Phase Efficacy- Crohn's Disease Activity Index (CDAI)
timeFrame: Week 12 and week 52
measure: Maintenance Phase Efficacy - Simple Endoscopic Score for Crohn's disease (SES-CD)
timeFrame: Week 52
measure: Maintenance Phase Efficacy - Endoscopic response
timeFrame: Week 52
measure: Maintenance Phase Efficacy - SES-CD ulcer subscore > 1
timeFrame: Week 52
measure: Maintenance Phase Efficacy - CDAI clinical remission
timeFrame: Week 52
measure: Maintenance Phase Efficacy - PRO-2 clinical remission
timeFrame: Week 52
measure: Maintenance Phase Efficacy - CDAI clinical response
timeFrame: Week 52
measure: Maintenance Phase Efficacy - PRO-2 clinical response
timeFrame: Week 52
measure: Maintenance Phase Efficacy - CDAI clinical response and endoscopic response
timeFrame: Week 52
measure: Maintenance Phase Efficacy - endoscopic remission
timeFrame: Week 52
measure: Extension Phase Safety- Adverse events
timeFrame: Weeks 64, 76, 88,100 and EOS
measure: Extension Phase Safety - Hematology and coagulation
timeFrame: Weeks 64, 76, 88,100 and EOS
measure: Extension Phase Safety - Biochemistry
timeFrame: Weeks 64, 76, 88,100 and EOS
Secondary outcomes:
measure: Induction Phase Efficacy - SES-CD
timeFrame: Week 12
measure: Induction Phase Efficacy - Endoscopic response
timeFrame: Week 12
measure: Induction Phase Efficacy-SES-CD ulcer subscore > 1
timeFrame: Week 12
measure: Induction Phase Efficacy-CDAI clinical remission
timeFrame: Week 12
measure: Induction Phase Efficacy-PRO-2 clinical remission
timeFrame: Week 12
measure: Induction Phase Efficacy-CDAI clinical response
timeFrame: Week 12
measure: Induction Phase Efficacy-PRO-2 clinical response
timeFrame: Week 12
measure: Induction Phase Efficacy-CDAI clinical response and endoscopic response
timeFrame: Week 12
measure: Induction Phase Efficacy - endoscopic remission
timeFrame: Week 12
Other outcomes:
Locations:
city: Fairhope
country: United States
facility: IMC Gulf Coast Gastroenterology, PC
state: Alabama
city: Scottsdale
country: United States
facility: Scottsdale Gastroenterology Specialists
state: Arizona
city: Sun City
country: United States
facility: GI Alliance -Gurnee
state: Arizona
city: Irvine
country: United States
facility: Hoag Hospital
state: California
city: Murrieta
country: United States
facility: United Medical Doctors
state: California
city: Colorado Springs
country: United States
facility: Peak Gastroenterology Associates
state: Colorado
city: Brandon
country: United States
facility: Clinical Research Of Brandon, LLC
state: Florida
city: Clearwater
country: United States
facility: West Central Gastroenterology d/b/a Gastro Florida
state: Florida
city: Lakeland
country: United States
facility: Auzmer Research
state: Florida
city: Miami Lakes
country: United States
facility: Wellness Clinical Research
state: Florida
city: Miami
country: United States
facility: Research Associates of South Florida, LLC
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute, Inc.
state: Florida
city: Ocala
country: United States
facility: Sarkis Clinical Trials - Parent
state: Florida
city: Orlando
country: United States
facility: Orlando Health, Inc.
state: Florida
city: Tampa
country: United States
facility: GCP Clinical Research, LLC
state: Florida
city: Temple Terrace
country: United States
facility: Theia Clinical Research Centers, LLC
state: Florida
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Health Care
state: Iowa
city: New Bedford
country: United States
facility: Lucida Clinical Trials, LLC
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts, Worcester
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Columbus Center
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Hilliard
country: United States
facility: OSU Inflammatory Bowel Disease Center
state: Ohio
city: Harrisburg
country: United States
facility: Susquehanna Research Group, LLC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
city: Uniontown
country: United States
facility: Frontier Clinical Research, LLC
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Medical Center, LLC
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Central Texas Clinical Research, LLC
state: Texas
city: Baytown
country: United States
facility: Inquest Clinical Research
state: Texas
city: Bellaire
country: United States
facility: Novel Research, LLC
state: Texas
city: Cedar Park
country: United States
facility: GI Alliance
state: Texas
city: Dallas
country: United States
facility: Baylor University Hospital
state: Texas
city: Garland
country: United States
facility: GI Alliance - Garland
state: Texas
city: Harlingen
country: United States
facility: Texas Digestive Specialists
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Mansfield
country: United States
facility: GI Alliance - Gurnee
state: Texas
city: San Antonio
country: United States
facility: Southern Star Research Institute, LLC
state: Texas
city: Tyler
country: United States
facility: Tyler Research Institute, LLC
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: Richmond VA Medical Center
state: Virginia
city: Roanoke
country: United States
facility: Gastroenterology Consultants of Southwest Virginia.
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Bruxelles
country: Belgium
facility: Hopital Universitaire de Bruxelles - Hopital Erasme
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Tournai
country: Belgium
facility: Centre Wallonie Picarde
city: Yvoir
country: Belgium
facility: CHU UCL Namur
city: Brno
country: Czechia
facility: SurGal Clinic s.r.o.
city: Brno
country: Czechia
facility: Vojenska nemocnice Brno
city: Hradec Králové
country: Czechia
facility: Hepato-Gastroenterologie HK s.r.o.
city: Olomouc
country: Czechia
facility: PreventaMed s.r.o.
city: Praha
country: Czechia
facility: ISCARE a.s.
city: Slaný
country: Czechia
facility: Nemocnice Slany
city: Amiens
country: France
facility: CHU Amiens
city: Besançon
country: France
facility: CHU Besançon - Hôpital Jean Minjoz
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand - Hopital d'Estaing
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Dijon
country: France
facility: CHU Dijon - Hôpital Bocage Central
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Michallon
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier Départemental Vendée - Les Oudairies
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre
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: Neuilly-sur-Seine
country: France
facility: Institut des MICI
city: Nice
country: France
facility: CHU Nice - Hôpital de l'Archet 2
city: Pessac
country: France
facility: CHU Bordeaux - Hôpital Haut-Lévêque
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Saint-Étienne
country: France
facility: CHU Saint Etienne - Hôpital Nord
city: Toulouse
country: France
facility: Hopital Rangueil
city: Vandœuvre-lès-Nancy
country: France
facility: Hôpital de Brabois
city: Berlin
country: Germany
facility: Charite-Campus Benjamin Franklin Medizin.Klin.I
city: Berlin
country: Germany
facility: Krankenhaus Waldfriede e. V.
city: Brandenburg an der Havel
country: Germany
facility: Universitaetsklinikum Brandenburg an der Havel
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
city: Frankfurt am Main
country: Germany
facility: Universitaetsklinikum Frankfurt Goethe-Universitaet
city: Hamburg
country: Germany
facility: Hamburgisches Forschungsinstitut fuer Chronisch Entzuendliche Darmerkrankungen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein - Campus Kiel
city: Ludwigshafen
country: Germany
facility: St. Marienkrankenhaus
city: Muenchen
country: Germany
facility: LMU - Campus Grosshadern
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
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: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Békéscsaba
country: Hungary
facility: Bekes Varmegyei Kozponti Korhaz
city: Gyöngyös
country: Hungary
facility: Gyongyosi Bugat Pal Korhaz
city: Szekszárd
country: Hungary
facility: Clinfan Szolgaltato Kft.
city: Székesfehérvár
country: Hungary
facility: Fejer Varmegyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Universitaria Renato Dulbecco di Catanzaro
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore Don Calabria
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Roma
country: Italy
facility: Università Campus Bio-Medico di Roma
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Sofferenza
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, Locatie AMC
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud UMC
city: Tilburg
country: Netherlands
facility: ETZ Elisabeth
city: Uden
country: Netherlands
facility: Bernhoven Uden
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Medis
city: Bydgoszcz
country: Poland
facility: NZOZ Centrum Medyczne KERmed
city: Kielce
country: Poland
facility: Polimedica Centrum Badań, Profilaktyki I Leczenia
city: Knurów
country: Poland
facility: Mz Badania Slowik Zymla Sp J
city: Kraków
country: Poland
facility: Centrum Medyczne Plejady
city: Leczna
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej w Lecznej
city: Nowy Targ
country: Poland
facility: ALLMEDICA sp. z o. o.
city: Opole
country: Poland
facility: Twoja Przychodnia Opolskie Centrum Medyczne
city: Piotrków Trybunalski
country: Poland
facility: Trialmed CRS
city: Poznan
country: Poland
facility: SOLUMED Centrum Medyczne
city: Poznań
country: Poland
facility: NSZOZ Termedica - Centrum Badan Klinicznych
city: Późna
country: Poland
facility: Twoja Przychodnia PCM
city: Rzeszów
country: Poland
facility: Gabinet Lekarski Bartosz Korczowski
city: Sosnowiec
country: Poland
facility: Kiepury Clinic MAŁGORZATA JARNOT SPECJALISTYCZNA PRAKTYKA GINEKOLOGICZNO-POŁOŻNICZA
city: Szczecin
country: Poland
facility: Twoja Przychodnia-Szczecinskie Centrum Medyczne Sp. z o. o.
city: Warszawa
country: Poland
facility: Centrum Zdrowia MDM
city: Warszawa
country: Poland
facility: Medical Network Spolka z o.o
city: Warszawa
country: Poland
facility: NZOZ VIVAMED Jadwiga Miecz
city: Wrocław
country: Poland
facility: Melita Medical Sp. Z O. O.
city: Zamość
country: Poland
facility: ETG Zamosc
city: Łódź
country: Poland
facility: AMICARE spółka z ograniczoną odpowiedzialnością spółka komandytowa
city: Świdnica
country: Poland
facility: DC-MED
city: Bucuresti
country: Romania
facility: S.C Delta Health Care S.R.L
city: Bucuresti
country: Romania
facility: SC Centrul Medical Medicum SRL, Specialitatea Gastroenterologie
city: Bucuresti
country: Romania
facility: Spitalul Clinic Colentina
city: Oradea
country: Romania
facility: S.C Pelican Impex S.R.L
city: Ploieşti
country: Romania
facility: Valahia Medical SRL
city: Banská Bystrica
country: Slovakia
facility: Fakultna nemocnica s poliklinikou F.D. Roosevelta
city: Bratislava
country: Slovakia
facility: Cliniq s.r.o.
city: Košice
country: Slovakia
facility: Endomed, s.r.o.
city: Nitra
country: Slovakia
facility: KM Management spol. s r.o.
city: Prešov
country: Slovakia
facility: Gastro I, s.r.o.
city: Rimavská Sobota
country: Slovakia
facility: Svet zdravia a.s.
city: Barcelona
country: Spain
facility: Centro Medico Teknon
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Fuenlabrada
country: Spain
facility: Hospital Universitario de Fuenlabrada
city: Huelva
country: Spain
facility: Hospital General Juan Ramon Jimenez
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Dr. Negrin
city: Santiago De Compostela
country: Spain
facility: Clinica Gaias - Santiago
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
References: