Comparison of Vedolizumab treatment to Adalimumab dose intensification in Crohn’s disease patients with loss of response or biomarker activity to Adalimumab on first line with therapeutic drug concentration: A randomized, multicentre, controlled VEDIAN trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Saint Etienne

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

27 May 2024 → ongoing

Decision date (initial)

2024-01-05

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

TAKEDA FRANCE S.A.S

External identifiers

EU CT number

2023-508154-25-00

ClinicalTrials.gov

NCT06180382

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluate the efficacy, in terms of clinical remission and biomarkers at week 24, of a therapeutic strategy using vedolizumab compared to a therapeutic strategy using optimized doses of adalimumab (ADA) in patients with CD experiencing secondary loss of response and/or presenting high biomarker activity and/or signs of activity on imaging (MRI or intestinal ultrasound or ileocolonoscopy or video capsule) under a standard maintenance dose of adalimumab treatment.

Secondary objectives 9

1. To evaluate the impact of a therapeutic strategy with Vedolizumab compared to a therapeutic strategy with Adalimumab (ADA) dose optimization on : Deep remission at W24 without treatment failure
2. To evaluate the impact of a therapeutic strategy with Vedolizumab compared to a therapeutic strategy with Adalimumab (ADA) dose optimization on : Treatment failure at W24 and W52
3. To evaluate the impact of a therapeutic strategy with Vedolizumab compared to a therapeutic strategy with Adalimumab (ADA) dose optimization on : Percentage of adverse events at W24 and W52
4. To evaluate the impact of a therapeutic strategy with Vedolizumab compared to a therapeutic strategy with Adalimumab (ADA) dose optimization on : Symptomatic remission at W24
5. To evaluate the impact of a therapeutic strategy with Vedolizumab compared to a therapeutic strategy with Adalimumab (ADA) dose optimization on : Evolution of IBDQ-32 quality-of-life score at W24
6. To evaluate the impact of a therapeutic strategy with Vedolizumab compared to a therapeutic strategy with Adalimumab (ADA) dose optimization on : clinical and biomarker remission rates at W12 and W52
7. To analyze CDST score for prediction of clinical remission and biomarkers at inclusion in each treatment arm.
8. To evaluate the impact of a therapeutic strategy with Vedolizumab compared to a therapeutic strategy with Adalimumab (ADA) dose optimization on : Mucosal remission healing rates at S24 and S52
9. Compare the efficacy of each strategy based on serum ADA levels at inclusion, defined in three groups: pharmacodynamic failure, pharmacokinetic failure, or immunogenic failure. Compare the efficacy of each strategy based on serum ADA levels at inclusion, defined in three groups: pharmacodynamic failure, pharmacokinetic failure, or immunogenic failure.

Conditions and MedDRA coding

Crohn's disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Major patient and having given consent to participate in the study
2. Patients with Crohn's disease who responded primarily to the originator or biosimilar adalimumab and have lost response to adalimumab (40 mg every two weeks)
3. Patient affiliated to or entitled under a social security scheme
4. If the subject is receiving oral corticosteroids other than budesonide or beclometasone dipropionate, the dose must be ≤ 20 mg/day of prednisone or its equivalent and have been stable for at least 2 weeks. The use of corticosteroids is prohibited after week 12.

Exclusion criteria 20

1. Pregnant woman
2. Patients with exclusive anoperineal Crohn's disease
3. Crohn's disease patient with transient or permanent stoma
4. Patients on intravenous corticosteroid therapy
5. Previous or current use of vedolizumab or ustekinumab for Crohn's disease
6. Concomitant use of immunomodulators
7. History of cancer
8. History of human immunodeficiency virus (HIV), immunodeficiency syndrome, central nervous system (CNS) demyelinating disease (including myelitis), neurological symptoms suggestive of demyelinating disease, chronic recurrent infection, active tuberculosis (received or untreated), severe infections such as sepsis and opportunistic infections.
9. Patient with ileoanal pouchitis or ileorectal anastomosis
10. Patient with short small bowel syndrome as determined by investigator
11. Patients receiving enteral nutrition
12. Patients receiving total parenteral nutrition (TPN).
13. Participation in a therapeutic study
14. Patient under legal protection or unable to give consent
15. Hemorrhagic rectocolitis or indeterminate colitis
16. Patient treated with a concomitant immunosuppressive agent at the time of inclusion. The patient may have been treated with an immunosuppressive agent, but this must have been discontinued at least 4 weeks prior to the screening visit.
17. Patient treated with an optimized dose of adalimumab
18. Primary non-responder to Adalimumab
19. Patient previously treated with ustekinumab before adalimumab
20. Severe relapse defined by CDAI > 330

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary objective will be to compare the proportion of clinical and biomarker remission (composite score) in the two groups of CD patients by 24 weeks after inclusion (ADA optimized versus Vedolizumab as second line).

Secondary endpoints 10

1. Compare deep remission defined as clinical remission (clinical activity score < 150 with fecal calprotectin < 250 mcg/g stools and CRP < 5mg/L and either CDEIS <3 using ileocolonoscopy or Lewis score < 135 in the small bowel using VCE or no disease activity on MRE (defined by segmental Maria score < 7) or no bowel thickness on US according to the previous tools used at inclusion at W24.
2. Compare treatment failure at W24 or W52 in the 2 groups
3. Compare the percentage of adverse events in both arms at W52
4. Symptomatic remission at W24 is a composite criterion measured by PRO2 defined as: Stool frequency (SF) < 3 with abdominal pain score (AP) < 2 at W24; AND absence of therapeutic failure between inclusion and W24.
5. Compare evolution of IBDQ-32 in the two groups of patients between inclusion and W24
6. Compare rates of clinical and biomarker remission at W12
7. Compare rates of clinical and biomarker remission at W52
8. Mucosal remission at week 24 will be defined by: • A CDEIS score < 3 at week 24 using ileocolonoscopy; • OR a Lewis score < 135 at week 24 in the small intestine using VCE (video capsule endoscopy); • OR no ulceration using VCE at week 24; • OR no activity on MRI at week 24 (defined by a segmental Maria score < 7); • OR no intestinal thickening on ultrasound at week 24 (< 3 mm with no other signs of activity).
9. Analyze the CDST (clinical decision support tool) score for prediction of remission under vedolizumab and adalimumab optimization.
10. Pharmacodynamic failure: Therapeutic blood ADA level (> 7.5 µg/mL) Pharmacokinetic failure: Subtherapeutic blood ADA level (< 7.5 µg/mL) Immunogenic failure (undetectable blood ADA level with presence of anti-ADA antibodies >50 ng/mL).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Saint Etienne

Sponsor organisation

Centre Hospitalier Universitaire De Saint Etienne

Address

Avenue Albert Raimond

City

Saint Priest En Jarez

Postcode

42270

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Saint Etienne

Contact name

Pr Xavier ROBLIN

Public contact point

Organisation

Centre Hospitalier Universitaire De Saint Etienne

Contact name

Pr Xavier ROBLIN

Locations

1 EU/EEA country · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications