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

Sponsor
Asan Medical Center (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT06051253
Collaborator
(none)
86
Enrollment
2
Arms
44.9
Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: TDM-based infliximab intravenous therapy
  • Drug: Standard infliximab intravenous therapy
 Phase 4

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 Design

Study Type:
Interventional
Anticipated Enrollment :
86 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Efficacy of Infliximab Treatment Based on TDM (Therapeutic Drug Monitoring) in Adult Patients With Active Perianal Fistulizing Crohn's Disease
Anticipated Study Start Date :
Oct 2, 2023
Anticipated Primary Completion Date :
Jun 30, 2026
Anticipated Study Completion Date :
Jun 30, 2027

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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

    1. 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.

    2. 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

    3. Biochemical remission [Week 54]

      The proportion of patients with biochemical remission (CRP [C-reactive protein] < 0.6 mg/dL)

    4. 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.

    5. 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.

    6. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    19 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    • 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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Asan Medical Center

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Byong Duk Ye, Professor, Asan Medical Center
    ClinicalTrials.gov Identifier:
    NCT06051253
    Other Study ID Numbers:
    • 20220573
    First Posted:
    Sep 22, 2023
    Last Update Posted:
    Sep 28, 2023
    Last Verified:
    Sep 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Crohn Disease
    Fistula
    Infliximab

    Study Results

    No Results Posted as of Sep 28, 2023