Stopping anti-TNF treatment in Crohn's and Colitis patients in remission

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Skane

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

5 May 2017 → ongoing

Decision date (initial)

2024-09-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-513299-17-00

EudraCT number

2016-000235-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

The aim is to identify clinical and biological markers that offer guidance as to which patients successfully may discontinue maintenance anti-TNF treatment, and which patients on the contrary need to continue treatment over an extended period of time in order to remain in remission.

Conditions and MedDRA coding

Ulcerative colitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. For patients with ulcerative colitis: • Diagnosis: Ulcerative colitis • Age 18-80 years. • Male or female. • IFX or ADA treatment since >12 months; last 3 doses at the same dose and interval. If the patient is on a biosimilar-infliximab the patient must have received at least 3 doses, and at the same dose and interval. • SCCAI score of ≤3. • Endoscopic Baron score of 0-1. The most inflamed part in the rectum/ sigmoid colon is evaluated. A minimum of 40 cm of the colon should be examined.
2. For patients with Crohn's disease: • Diagnosis: Crohn's disease • Age 18-80 years. • Male or female. • IFX or ADA treatment since >12 months; last 3 doses at the same dose and interval. If the patient is on a biosimilar-infliximab the patient must have received at least 3 doses, and at the same dose and interval. • Simplified HBI (sHBI; abdominal palpation excluded) score of ≤4. • Simplified Endoscopic Score for CD (SES-CD) of ≤4 and no ulcer ≥5 mm other than a potential anastomotic ulcer (ie apthous ulcers allowed). • F-calprotectin <200 mg/kg (PhiCal) or <350 mg/kg (Buhlmann).

Exclusion criteria 4

1. Pregnancy
2. Corticosteroid (rectal or systemic) or rectal 5-ASA treatment during the last 6 months.
3. For patients with ulcerative colitis: Colonic resection.
4. For patients with Crohn's disease: Documented engagement/inflammation of the small bowel proximally of a level of 50 cm from the ileocecal valve. Any examination modality is accepted, and a current/new small intestinal examination is not required. A limited number of small (<5 mm) lesions on capsule endoscopy allowed. Colonic surgery with removal of more than half of the transverse colon.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients that relapses, as defined by symptomatic scoring in combination with endoscopy, at 12 and 24 months after discontinuation of anti-TNF treatment with identification of factors at study-start that correlate positively or negatively with the event of relapse.

Secondary endpoints 17

1. Endoscopic scores at 12 and 24 months among those who relapsed compared to those who remained in remission.
2. Fecal calprotectin levels at 12 and 24 months among those who relapsed compared to those who remained in remission.
3. Fecal calprotectin levels at study start among ulcerative colitis patients who relapsed compared to those who remained in remission.
4. The rate of relapse among ulcerative colitis patients with the following fecal calprotectin level ranges (<30 mg/kg for Calpro [C] and <60 mg/kg for Buhlmann [B]; 30-99 mg/kg C and 60-199 mg/kg B; 100-299 mg/kg C and 200-599 mg/kg B; ≥300 mg/kg C and ≥600 mg/kg B.
5. The optimal fecal calprotectin level cut-off with regards to sensitivity and specificity for relapse, for ulcerative colitis and Crohn's disease patients, respectively.
6. Trough concentrations of infliximab and adalimumab among those who relapsed compared to those who remained in remission.
7. The rate of relapse among those with undetectable infliximab or adalimumab trough concentrations, those with 0.5-2.9 ug/ml, 3.0-7.0 ug/ml, >7.0 ug/ml for infliximab, and ≥10.0 ug/ml for adalimumab.
8. The optimal trough concentration cut-off with regards to sensitivity and specificity for relapse, for infliximab and adalimumab, respectively.
9. Area under the infliximab or adalimumab concentration curve during the last therapy cycle among those who relapsed compared to those who remained in remission.
10. Presence of anti-drug antibodies among those who relapsed compared to those who remained in remission.
11. The rate of relapse among those with anti-drug antibodies versus those without.
12. Time to relapse among those who relapse, comparing ADA versus IFX treated and UC versus CD.
13. The level of gut microbiota dysbiosis among those who relapsed compared to those who remained in remission.
14. The rate of relapse among those with a dysbiosis score of 1, 2-3, and 4-5, respectively.
15. Correlation analyses of genes showing high versus low expression in mucosal biopsies and blood samples, with the event of relapse.
16. Correlation analyses of gene-variants with the event of relapse.
17. Additional factors that will be correlated with relapse rates: Endoscopic scores; corticosteroid use between 12 and 6 months before baseline; previous anti-TNF treatment; dose intensification of anti-TNF treatment; mono- versus concomitant immunomodulatortreatment; previously maximal inflammatory extent (Montreal classification); disease duration; extraintestinal manifestations; gender; smoking; hemoglobin; white blood cell count; platelet count; CRP; and histology/immunohistochemistry.

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Skane

Sponsor organisation

Region Skane

Address

Dockplatsen 26, Malmo S:t Petri Malmo S:t Petri

City

Malmo

Postcode

211 74

Country

Sweden

Scientific contact point

Organisation

Region Skane

Contact name

Jan Marsal

Public contact point

Organisation

Region Skane

Contact name

Jan Marsal

Locations

1 EU/EEA country · 4 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 12 files

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

Application history

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