Clinical trial NCT06257706: VECTORS - A Study to Evaluate Transmural Healing as a Treatment Target in Crohn's Disease
Official title: An Interventional Study to Evaluate Treating to a Target of Transmural Healing in Patients With Moderately to Severely Active Crohn's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Moderately to Severely Active Crohn's Disease
Crohn Disease
Disease Crohn
Lead sponsor: Alimentiv Inc.
Sponsor class: OTHER
Collaborators: name: Takeda
First posted: 2024-02-14
Enrollment: 304
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is an interventional, randomized, parallel-group, multicenter, controlled study. A total of approximately 304 participants with moderately-to-severely active CD from multiple international sites will be enrolled into this study. All qualified participants will be randomly assigned in a 1:1 ratio to one of 2 different treatment target groups: Group 1 will be treated over 48 weeks to achieve a target of corticosteroid-free IUS-based outcomes + clinical remission + biomarker remission. Group 2 will be treated over 48 weeks to achieve a target of corticosteroid-free clinical remission + biomarker remission. Randomization will be stratified by the following baseline factors: prior exposure to an approved biologic/small molecule advanced therapy for CD (yes or no), disease location (ileal or colonic), and disease duration (≤ 2 years or \>2 years, based on the date of diagnosis).
Primary purpose: TREATMENT

Brief summary: Transmural healing (TMH) is recognized as a potentially important measure of Crohn's disease (CD) activity but not a formal target. Observational studies suggest that TMH may be associated with better long-term outcomes. The study will evaluate TMH using noninvasive intestinal ultrasound (IUS), a patient-friendly technique that can be performed routinely in clinical practice. The aim of the study is to determine if treating to a target of corticosteroid-free (CS-free) IUS outcomes + clinical symptoms + biomarkers is superior to a target of clinical symptoms + biomarkers alone in achieving CS-free endoscopic remission measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD).

Qualified participants will be randomly assigned in a 1:1 ratio to one of 2 different target treatment groups.

Group 1: Participants will be treated over 48 weeks to achieve a target of corticosteroid-free IUS-based outcomes + clinical remission + biomarker remission. At Week 22 and 30, the IUS-based component of the target will be IUS response and at Week 38, the final treatment target will be TMH. Group 2: Participants will be treated over 48 weeks to achieve a target of corticosteroid-free clinical remission + biomarker remission.


Eligibility criteria: Inclusion Criteria:

Participants must meet all of the following criteria for enrolment into the study:

1. Adults aged 18 to 80 years, inclusive, at the time of consent;
2. Moderately-to-severely active CD at baseline defined by a CDAI score of 220 to 450 inclusive and SES-CD, excluding the presence of narrowing component, ≥6 (or ≥4 for participants with isolated ileal disease);
3. CRP of ≥5 mg/L and/or FCal ≥250 μg/g at Screening;
4. BWT on IUS of \>4.0 mm in the ileum or any colonic segment (excluding the rectum);
5. Biologic-naïve or have previous exposure to no more than 1 advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD. Note: only approximately 15% to 30% of the enrolled population will have had prior exposure to an advanced therapeutic;
6. Participants may continue stable dose (initiated at least 4 weeks prior to Screening) of 5-ASA for CD;
7. Persons of childbearing potential must have a negative serum pregnancy test prior to randomization and must use a highly effective method of contraception throughout the study.

   Females unable to bear children must have documentation of such in the source records;
8. Able to participate fully in all aspects of this clinical trial;
9. Written informed consent must be obtained and documented.

Exclusion Criteria:

Participants who exhibit any of the following conditions are to be excluded from the study:

1. Current or previous treatment with vedolizumab, etrolizumab, or natalizumab;
2. Previously exposed to 2 or more compounds of an advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD;
3. Change to oral corticosteroid therapy dosing within 2 weeks prior to randomization or a corticosteroid dose of \>40 mg of prednisone or equivalent at randomization;
4. Only have inflammation proximal to the terminal ileum that cannot be reached by ileocolonoscopy;
5. Have a CD complication, such as symptomatic strictures in the small bowel with \>3 cm prestenotic dilatation on any imaging modality, requiring procedural intervention;
6. Previous extensive colonic resection or missing \>2 segments out of 5 (terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum), ileorectal anastomosis, or a proctocolectomy;
7. Ostomy or ileoanal pouch;
8. Short bowel syndrome;
9. Fibrotic only stricture in the ileum or colon without evidence of active inflammation (in the investigator's judgment), including any impassable stenosis;
10. Abscess \>2 cm, detected incidentally by IUS, but participants with draining fistulas are not excluded;
11. Serious underlying disease other than CD that, in the opinion of the investigator, may interfere with the participant's ability to participate fully in the study or would compromise participant safety;
12. Positive stool test for Clostridioides difficile infection (as demonstrated by positive toxin);
13. Known HIV or hepatitis B or C infection. If a negative test result is available in the 12 months prior to randomization, retesting is not required;
14. Known active or latent tuberculosis (TB); if a negative test result is available in the 12 months prior to randomization, confirmatory testing (per standard of care) is not required before randomization;
15. Other systemic or opportunistic infection (including cytomegalovirus), any other clinically significant extraintestinal infection, or recurring infection within 6 months of randomization;
16. Has active cerebral/meningeal disease, signs, symptoms, or any history of progressive multifocal leukoencephalopathy (PML) prior to randomization;
17. Hypersensitivity, allergy, or intolerance to any excipient of vedolizumab or any other contraindication to vedolizumab;
18. Active severe infection such as sepsis, cytomegalovirus, listeriosis, or opportunistic infection;
19. Unwillingness to withhold protocol-prohibited medications during the trial;
20. Concurrent or previous participation in another clinical trial and received any investigational therapy within 30 days or 5 half-lives (whichever is longer) prior to randomization;
21. History of alcohol or drug abuse that in the opinion of the investigator may interfere with the participant's ability to comply with the study procedures;
22. Prior enrolment in the current study and had received study treatment;
23. Pregnant, lactating, or intending to become pregnant/impregnate a partner before, during, or within 18 weeks after the last dose; or intending to donate ova or sperm during such time period;
24. Vaccination with a live or live-attenuated vaccine within 4 weeks prior to randomization, or planned vaccination with a live or live-attenuated vaccine during participation in the study;
25. Any person performing mandatory military service, deprived of liberty, in a residential care setting, or any person who, due to a judicial decision, cannot take part in clinical studies;
26. The person is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling).

Primary outcomes:
measure: Percentage of participants with Corticosteroid-free Endoscopic remission in group 1 and group 2 at week 48
timeFrame: week 48
Secondary outcomes:
measure: Percentage of participants with Corticosteroid-free Transmural healing (TMH)+Endoscopic remission+Clinical remission in group 1 and group 2 at week 48
timeFrame: week 48
measure: Percentage of participants with Corticosteroid-free IUS response+Endoscopic remission+Clinical Remission in group 1 and group 2 at week 48
timeFrame: week 48
measure: Percentage of participants with Corticosteroid-free Endoscopic remission+Clinical Remission in group 1 and group 2 at week 48
timeFrame: week 48
measure: Percentage of participants with Corticosteroid-free endoscopic response+Clinical response in group 1 and group 2 at week 48
timeFrame: week 48
measure: Percentage of participants with Corticosteroid-free clinical remission in group 1 and group 2 at Week 14, Week 22 and Week 48.
timeFrame: week 14, week 22 and week 48
measure: Percentage of participants with Corticosteroid-free Clinical Response in group 1 and group 2 at week 14, week 22 and week 48
timeFrame: week 14, week 22 and week 48
measure: Crohn's Disease Activity Index(CDAI) total score and corresponding change from baseline during follow-up (Week 6, Week 14, Week 22, Week 30, Week 38, Week 48, Week 64, Week 80, Week 96) in group 1 and group 2
timeFrame: week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96
measure: Percentage of participants with Corticosteroid-free endoscopic response in group 1 and group 2 at week 48
timeFrame: week 48
measure: SES-CD total score and corresponding change from baseline to Week 48 in group 1 and group 2
timeFrame: week 48
measure: Percentage of participants with Transmural healing (TMH) in group 1 and group 2 at week 48
timeFrame: week 48
measure: Percentage of participants with Intestinal Ultrasound (IUS) response in group 1 and group 2 at Week 48
timeFrame: week 48
measure: Bowel Wall Thickness (BWT) measured by Intestinal Ultrasound (IUS) in mm and corresponding change from baseline at Week 48 in group 1 and group 2.
timeFrame: week 48
measure: Color Doppler signal (CDS) and corresponding change from baseline at Week 48 in group 1 and group 2.
timeFrame: week 48
measure: International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) (per segment as well as total) and corresponding change from baseline at Week 48 in group 1 and group 2
timeFrame: week 48
measure: Percentage of participants with Transmural healing (TMH) at week 14, week 22, week 30, week 38, and week 48 in group 1
timeFrame: week 14, week 22, week 30, week 38, week 48
measure: Percentage of participants with Intestinal Ultrasound (IUS) response at week 14, week 22, week 30, week 38, and week 48 in group 1
timeFrame: week 14, week 22, week 30, week 38, week 48
measure: Bowel Wall Thickness (BWT) measured by Intestinal Ultrasound (IUS) in mm and corresponding change from baseline at week 14, week 22, week 30, week 38, and week 48 in group 1
timeFrame: week 14, week 22, week 30, week 38, week 48
measure: Color Doppler signal (CDS) and corresponding change from baseline at week 14, week 22, week 30, week 38, and week 48 in group 1
timeFrame: week 14, week 22, week 30, week 38, week 48
measure: International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) (per segment as well as total) and corresponding change from baseline at week 14, week 22, week 30, week 38, and week 48 in group 1
timeFrame: week 14, week 22, week 30, week 38, week 48
measure: Percentage of participants with Histologic remission at week 48 in group 1 and group 2
timeFrame: week 48
measure: Percentage of participants with Histologic response at week 48 in group 1 and group 2
timeFrame: week 48
measure: Percentage of patients with Biomarker remission at week 48, week 64, week 80 and week 96 in group 1 and group 2
timeFrame: week 48, week 64, week 80, week 96
measure: Percentage of patients with Biomarker response at week 48, week 64, week 80 and week 96 in group 1 and group 2
timeFrame: week 48, week 64, week 80, week 96
measure: Percentage of participants with C-reactive protein (CRP) response during follow-up (Week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2
timeFrame: week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96
measure: Percentage of participants with fecal calprotectin (FCal) response during follow-up (Week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2
timeFrame: week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96
measure: Changes in C-reactive protein (CRP) from baseline during follow-up (Week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2
timeFrame: week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96
measure: Changes in fecal calprotectin (FCal) from baseline during follow-up (Week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2
timeFrame: week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96
measure: 2-item Patient-Reported Outcome (PRO-2) score and corresponding changes from baseline during follow-up (Weeks 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2
timeFrame: week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96
measure: Symptoms and Impacts Questionnaire for CD (SIQ-CD) score and corresponding changes from baseline during follow-up (Weeks 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2
timeFrame: week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96
measure: Urgency Numerical Rating Score (NRS) and corresponding changes from baseline during follow-up (Weeks 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2
timeFrame: week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96
measure: Inflammatory Bowel Disease Questionnaire (IBDQ) score and corresponding changes from baseline during follow-up (Weeks 30, week 48 and week 96) in group 1 and group 2
timeFrame: week 30, week 48, week 96
measure: Time to CD-related complication from randomization through Week 96 in group 1 and group 2
timeFrame: from randomization through Week 96
measure: Time to each component of CD-related complication in group 1 and group 2
timeFrame: from randomization through Week 96
measure: Percentage of participants who switched to an alternate biologic (yes/no) by Week 48 and Week 96
timeFrame: week 48, week 96
measure: Exposure-adjusted incidence rates of serious adverse events (SAEs), all adverse events (AEs), and AEs of special interest (AESIs) in group 1 and group 2
timeFrame: up to week 96
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: TLC Clinical Research Inc - Los Angeles
state: California
city: Liberty
country: United States
facility: BVL Research- Missouri
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center Investigational Pharmacy
state: New Hampshire
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Misericordiae Ltd
state: Queensland
city: Adelaide
country: Australia
facility: Calvary Adelaide Hospital
state: South Australia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Epping
country: Australia
facility: Northern Hospital Epping
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Harry Perkins institute of Medical Research - Fiona Stanley Hospital
state: Western Australia
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
state: Western Australia
city: Sint-Niklaas
country: Belgium
facility: VITAZ - AZ Nikolaas
state: Antwerpen
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis Bonheiden
state: Antwerp
city: Ghent
country: Belgium
facility: University Hospital Ghent
state: East Flanders
city: Leuven
country: Belgium
facility: UZ Leuven-University Hospital Gasthuisberg
state: Flemish Brabant
city: Roeselare
country: Belgium
facility: AZ Delta - Rumbeke Campus
state: West Flanders
city: Brussels
country: Belgium
facility: ULB Hopital Erasme
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta, Dept of Medicine, Division of Gastroenterology
state: Alberta
city: Bridgewater
country: Canada
facility: Viable Clinical Research - Bridgewater
state: Nova Scotia
city: London
country: Canada
facility: LHSC - University Campus
state: Ontario
city: London
country: Canada
facility: LHSC - Victoria Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Immune and Digestive Health Institute Inc. (TIDHI)
state: Ontario
city: Brno
country: Czechia
facility: Vojenska nemocnice Brno
state: South Moravian
city: Brno
country: Czechia
facility: Fakultni Nemocnice Brno
state: South Moravian
city: Copenhagen NV
country: Denmark
facility: Bispebjerg Hospital
state: Capital
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
state: Capital
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital
state: Central Denmark
city: Randers
country: Denmark
facility: Randers Regional Hospital
state: Central Denmark
city: Herlev
country: Denmark
facility: Herlev Hospital
state: Hovedstaden
city: Hillerod
country: Denmark
facility: Nordsjaellands Hospital - Hillerod
state: Hovedstaden
city: Koge
country: Denmark
facility: Sjaellands Universitets hospitall Koge
state: Zealand
city: Svendborg
country: Denmark
facility: Svendborg Hospital
city: Pierre-Bénite
country: France
facility: Hopital Lyon Sud
state: Auvergne-Rhone-Alpes
city: Marseille
country: France
facility: APHM
state: Provence-Alpes-Cote d'Azur
city: Neuilly sur Seine
country: France
facility: Groupe Hospitalier Prive Ambroise Pare - Hartmann
city: Augsburg
country: Germany
facility: Universitatsklinikum Augsburg
state: Bavaria
city: Frankfurt am Main
country: Germany
facility: Universitatsklinkum Frankfurt - Goethe Universitat
state: Hesse
city: Luneburg
country: Germany
facility: Klinikum Luneburg
state: Lower Saxony
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein (UKSH)- Campus Kiel
state: Schleswig-Holstein
city: Freiburg
country: Germany
facility: Universitats Klinikum Freiburg
city: San Giovanni Rotondo
country: Italy
facility: Ospedale Casa Sollievo della Sofferenza IRCCS
state: Foggia
city: Milano
country: Italy
facility: Ospedale Luigi Sacco
state: Lombardia
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.I.
state: Milan
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
state: Rome
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
state: Gelderland
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - VU Medisch Centrum
state: North Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum (MC)
state: South Holland
city: Tilburg
country: Netherlands
facility: ETZ - St. Elisabeth Hospital
city: Leczna
country: Poland
facility: Oddzial Gastroenterologiczny SP ZOZ w Lecznej
state: Gmina Leczna
city: Poznań
country: Poland
facility: SOLUMED Centrum Medyczne
state: Greater Poland
city: Torun
country: Poland
facility: GASTROMED - Kopon, Zmudzinski I Wspolnicy Sp.j.
state: Kuyavian-Pomeranian
city: Wroclaw
country: Poland
facility: Melita Medical Sp Zoo
state: Lower Silesian
city: Warsaw
country: Poland
facility: WIP Warsaw IBD Point Profesor Kierkus
state: Masovia
city: Warszawa
country: Poland
facility: Bodyclinic Sp.z.o.o. Sp.K
state: Masovia
city: Rzeszów
country: Poland
facility: Centrum Medyczne Medyk
state: Podkarpackie
city: Katowice
country: Poland
facility: Vita Longa Sp. z o.o.
state: Silesian
city: Szczecin
country: Poland
facility: Sonomed Sp. z o.o. - Centrum Medyczne
state: West Pomerianian
city: Opole
country: Poland
facility: Twoja Przychodnia-Centrum Medyczne Opole
city: Wrocław
country: Poland
facility: EuroMediCare (EMC) Instytut Medyczny SA
city: Lisboa
country: Portugal
facility: Hospital da Luz Lisboa
city: Lisbon
country: Portugal
facility: LisbonCentro Hospitalar Lisboa Norte, EPE- Hospital de Santa Maria
city: Loures
country: Portugal
facility: Hospital Beatriz Angelo
city: Viseu
country: Portugal
facility: Centro Hospitalar de Tondela Viseu - Sao Teotonio Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust - QMC
state: East Midlands
city: Harrow
country: United Kingdom
facility: London North West University Healthcare NHS Trust - Northwick Park Hospital
state: Middlesex
city: London
country: United Kingdom
facility: Barts Health NHS Trust - The Royal London Hospital
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Kings College Hospital NHS Foundation Trust
Study officials:
affiliation: Alimentiv Inc.
name: Vipul Jairath, MD
role: PRINCIPAL_INVESTIGATOR
References: