TDM-based Infliximab Treatment for Active Perianal Fistulizing Crohn's Disease

Phase 4

Recruiting

• Conditions: Crohn Disease; Infliximab; Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease Score; Therapeutic Drug Monitoring; Perianal Fistula Due to Crohn's Disease
• Interventions: Drug: TDM-based infliximab intravenous therapy; Drug: Standard infliximab intravenous therapy

• Registration Number: NCT06051253
• Lead Sponsor: Asan Medical Center

Brief Summary

This study will compare the efficacy and safety of TDM (therapeutic drug monitoring)-based infliximab (CT-P13, RemsimaTM) intravenous therapy compared with the standard infliximab (RemsimaTM) intravenous therapy for patients with active perianal fistulzing Crohn's disease.

Detailed Description

The TDM-based group: At week 0,2, and 6, infliximab (RemsimaTM) is intravenously administered at a dose of 5 mg/kg. From week 14 to 46 (at week 14, 22, 30, 38, and 46), infliximab dose can be increased to 10 mg/kg, targeting trough level (TL) of infliximab 10 mcg/mL or over (If TL is 10 mcg/mL or over under treatment with 5 mg/kg infliximab, 5 mg/kg of infliximab is continued. If TL is lower than 10 mcg/mL, infliximab dose is increased to 10 mg/kg). Once infliximab dose was increased to 10 mg/kg, the next doses are fixed to 10 mg/kg.

The standard group: Infliximab (RemsimaTM) is intravenously administered at a dose of 5 mg/kg at week 0, 2, 6, 14, 22, 30, 38, and 46. Therapeutic dose monitoring (TDM, checking trough levels of infliximab) is performed at week 14, 22, 30, 38, and 46, but TDM results are not reflected in determining doses of infliximab.

The co-primary endpoints of the study will be 1) Clinical remission (both week 50 and week 54), 2) Changes of MAGNIFI-CD (Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease) score compared with the baseline score (week 54)

Study Timeline

• Study First Submitted: 2023-09-10
• Study First Submitted QC: 2023-09-20
• Study First Posted: 2023-09-22
• Study Start: 2023-11-01
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-11
• Last Update Posted: 2024-05-14
• Primary Completion: 2026-06-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 86

Inclusion Criteria

1. Age: 19-80 years
2. Subjects diagnosed with perianal fistulizing Crohn's disease based on clinical, endoscopic, histological, and radiologic findings, etc.
3. Subjects naive to both biological drugs (anti-TNFs, anti-integrin, anti-IL12/23, etc.) and investigational new drugs
4. Subjects with at least one draining perianal fistula
5. Subjects not responding to two or more conventional treatments (antibiotics, drainage, immunosuppressants, etc.)
6. Women with a childbearing potential: Those who agree to follow contraception during study drug administration and for at least 6 months from the last dosing of the study medication

Exclusion Criteria

1. In cases where written informed consents cannot be provided by the study subjects or the subjects' legally acceptable representative
2. Subject with a probability of receiving bowel surgery within 12 weeks after baseline, decided by investigators
3. Subjects with temporary or permanent stoma
4. Subjects with short bowel syndrome
5. Subjects not eligible due to significant bowel strictures or intra-abdominal abscesses
6. Subjects who received bowel surgery within 6 months of baseline or subjects who were admitted due to complications associated with bowel strictures or intra-abdominal abscesses within 3 months of baseline
7. Subjects with enterovaginal fistula, enterocutaneous fistula, or enteroenteric fistula
8. Subjects previously exposed to biologics (anti-TNFs, anti-integrin, anti-IL12/23, etc.) or investigational new drugs
9. Subjects with a history of hypersensitivity to monoclonal antibody
10. Subjects requiring corticosteroid therapy. However, if oral corticosteroid dose lower or equivalent to prednisolone 20 mg/day before baseline is given and tapering of oral corticoseroid from baseline is planned, that subjects can be included in the study. Oral corticoseroid is tapered at a schedule of prednisolone 5 mg/7 days (example: if the subject was on oral prednisolone 20 mg/day before baseline, oral prednisolone is tapered as follows: 15 mg/day x 7 days -> 10 mg/day x 7 days -> 5 mg/day x 7 days -> stopping of prednisolone)
11. Subjects with active tuberculosis. However, if the subject has a history of tuberculosis, which was cured with standard anti-tuberculosis therapy according to the standard anti-tuberculosis treatment guidelines, that subject can be included
12. Subjects with latent tuberculosis: Subjects determined to be positive for latent tuberculosis by the pulmonology specialist after history taking, physical examination, chest X-ray, and interferon gamma release assay during the screening period. However, even if positive for latent tuberculosis, if 4 week-treatment for latent tuberculosis is completed and if further treatment for latent tuberculosis is planned to be completed, that subject can be included
13. Subjects positive for HBsAg. In cases of HBsAg (-), but with IgG Anti-HBc (+), real time quantitative PCR for HBV DNA is required. If HBV DNA is 10 IU/mL or over, that subject should be excluded
14. Subjects positive for anti-HCV antibody
15. Subjects with a history of infection with HIV or subject positive for HIV Ag
16. Subjects positive for Clostridioides difficile toxin assay or Clostridioides difficile culture assay
17. Subjects with a heart disease of NYHA Class III/IV
18. Subjects with current or previous demyelinating disease
19. Subject with a history of malignancy (excluding skin basal cell carcinoma, skin squamous cell carcinoma, and uterine cervix cancer) within 5 years or with a history of dysplasia of colon or small bowel within 5 years.
20. Subjects with symptoms or signs of active infection or with a history of treatment for infection within 8 weeks
21. Subjects with a history of organ transplantation
22. Pregnant or lactating women
23. Non-Korean ethnicity according to a family tree
24. Subjects decided to be not eligible for the study by investigators

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TDM-based group	TDM-based infliximab intravenous therapy	At week 0,2, and 6, infliximab (CT-P13, RemsimaTM) is intravenously administered at a dose of 5 mg/kg. From week 14 to 46 (at week 14, 22, 30, 38, and 46), infliximab dose can be increased to 10 mg/kg, targeting trough level (TL) of infliximab 10 mcg/mL or over (If TL is 10 mcg/mL or over under treatment with 5 mg/kg infliximab, 5 mg/kg of infliximab is continued. If TL is lower than 10 mcg/mL, infliximab dose is increased to 10 mg/kg). Once infliximab dose was increased to 10 mg/kg, the next doses are fixed to 10 mg/kg.
Standard group	Standard infliximab intravenous therapy	Infliximab (CT-P13, RemsimaTM) is intravenously administered at a dose of 5 mg/kg at week 0, 2, 6, 14, 22, 30, 38, and 46. Therapeutic dose monitoring (TDM, checking trough levels of infliximab) is performed at week 14, 22, 30, 38, and 46, but TDM results are not reflected in determining doses of infliximab.

Primary Outcome Measures

Name	Time	Method
Proportion of participants in clinical remission	Both week 50 and 54	Clinical remission is defined as no draining perianal fistula on gentle finger compression by a surgeon, without a seton. To be classified as clinical remission, participants should show no draining perianal fistula on gentle finger compression by a surgeon, without a seton at both week 50 and week 54.
Change of the MAGNIFI-CD (Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease) score	Week 54	MAGNIFI-CD = 3 x Number of fistula tract (3 levels) + 2 x Hyperintensity of primary tract on post-contrast T1-weighted images (2 levels) + 2 x Dominant feature (3 levels) + 2 x Fistula length (3 levels) + 2 x Extension (3 levels) + 1 x Inflammatory mass (6 levels).; Range of values: 0 \~ 25 High values mean more active perianal fistula

Secondary Outcome Measures

Name	Time	Method
Biochemical remission	Week 54	The proportion of patients with biochemical remission (CRP \[C-reactive protein\] \< 0.6 mg/dL)
Proportion of participants in clinical response	Week 54	Clinical response is defined as 50% or more decrease of the number of draining fistula or of draining amount on gentle finger compression by a surgeon, without a seton.
The median level of infliximab	Week 22, 30, 38, 46 and 54	Infliximab level is measured by the the Quantum Blue® Infliximab assay measure and is expressed as mcg/mL. In each group, infliximab trough levels of week 22, 30, 38, 46 and 54 are summarized and median value with interquartile ranges are calculated. Between two groups, those median values are compared.
Change of IBDQ (Inflammatory Bowel Disease Questionnaire) score	Week 54	The IBDQ (Inflammatory Bowel Disease Questionnaire) gives a possible score range of 32 to 224, where a higher score indicates better health-related quality of life. IBDQ is measured at week 14 and week 54.
The proportion of patients with safety issues (adverse events)	Week 54	Comparing the proportions of patients having any adverse events, serious adverse events, serious infections, and all types of adverse events
The proportion of patients with MAGNIFI-CD (Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease) score of 0	Week 54	MAGNIFI-CD = 3 x Number of fistula tract (3 levels) + 2 x Hyperintensity of primary tract on post-contrast T1-weighted images (2 levels) + 2 x Dominant feature (3 levels) + 2 x Fistula length (3 levels) + 2 x Extension (3 levels) + 1 x Inflammatory mass (6 levels).; Range of values: 0 \~ 25 High values mean more active perianal fistula

Trial Locations

Locations (1)

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of