Clinical trial NCT06051253: TDM-based Infliximab Treatment for Active Perianal Fistulizing Crohn's Disease
Official title: Efficacy of Infliximab Treatment Based on TDM (Therapeutic Drug Monitoring) in Adult Patients With Active Perianal Fistulizing Crohn's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Crohn Disease
Infliximab
Perianal Fistula Due to Crohn's Disease
Therapeutic Drug Monitoring
Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease Score
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2023-09-22
Enrollment: 86
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

Eligibility criteria: * 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

Primary outcomes:
measure: Proportion of participants in clinical remission
timeFrame: Both week 50 and 54
measure: Change of the MAGNIFI-CD (Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease) score
timeFrame: Week 54
Secondary outcomes:
measure: Proportion of participants in clinical response
timeFrame: Week 54
measure: The proportion of patients with MAGNIFI-CD (Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease) score of 0
timeFrame: Week 54
measure: Biochemical remission
timeFrame: Week 54
measure: The median level of infliximab
timeFrame: Week 22, 30, 38, 46 and 54
measure: Change of IBDQ (Inflammatory Bowel Disease Questionnaire) score
timeFrame: Week 54
measure: The proportion of patients with safety issues (adverse events)
timeFrame: Week 54
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Byong Duk Ye, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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