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

May 11, 2024 updated by: Byong Duk Ye, Asan Medical Center

Efficacy of Infliximab Treatment Based on TDM (Therapeutic Drug Monitoring) in Adult Patients With Active Perianal Fistulizing Crohn's Disease

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

86

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TDM-based group
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.
Drug: TDM-based infliximab intravenous therapy
Infliximab (CT-P13, RemsimaTM) is intravenously given as an induction therapy at a dose of 5 mg/kg at week 0, 2, and 6. 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.
Other Names:
  • TDM-based infliximab (CT-P13, RemsimaTM) intravenous therapy
Active Comparator: Standard group
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.
Drug: 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.
Other Names:
  • Standard infliximab (CT-P13, RemsimaTM) intravenous therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of the MAGNIFI-CD (Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease) score
Time Frame: 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
Week 54
Proportion of participants in clinical remission
Time Frame: 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.
Both week 50 and 54

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The proportion of patients with MAGNIFI-CD (Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease) score of 0
Time Frame: 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
Week 54
Biochemical remission
Time Frame: Week 54
The proportion of patients with biochemical remission (CRP [C-reactive protein] < 0.6 mg/dL)
Week 54
The median level of infliximab
Time Frame: 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.
Week 22, 30, 38, 46 and 54
Change of IBDQ (Inflammatory Bowel Disease Questionnaire) score
Time Frame: 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.
Week 54
Proportion of participants in clinical response
Time Frame: 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.
Week 54
The proportion of patients with safety issues (adverse events)
Time Frame: Week 54
Comparing the proportions of patients having any adverse events, serious adverse events, serious infections, and all types of adverse events
Week 54

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asan Medical Center

Investigators

  • Principal Investigator: Byong Duk Ye, MD, PhD, Asan Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2023

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

September 10, 2023

First Submitted That Met QC Criteria

September 20, 2023

First Posted (Actual)

September 22, 2023

Study Record Updates

Last Update Posted (Actual)

May 14, 2024

Last Update Submitted That Met QC Criteria

May 11, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20220573

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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