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

NCT06051253 | Recruiting Phase 4

• 1 other identifier: 20220573
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• Proportion of participants in clinical remission

  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

• Change of the MAGNIFI-CD (Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease) score

  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

Secondary Outcomes (6)

• Proportion of participants in clinical response

  Week 54

• The proportion of patients with MAGNIFI-CD (Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease) score of 0

  Week 54

• Biochemical remission

  Week 54

• The median level of infliximab

  Week 22, 30, 38, 46 and 54

• Change of IBDQ (Inflammatory Bowel Disease Questionnaire) score

  Week 54

Study Arms (2)

TDM-based group

EXPERIMENTAL

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

Standard group

ACTIVE COMPARATOR

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

Interventions

TDM-based infliximab intravenous therapy DRUG

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.

Also known as: TDM-based infliximab (CT-P13, RemsimaTM) intravenous therapy

TDM-based group

Standard infliximab intravenous therapy DRUG

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.

Also known as: Standard infliximab (CT-P13, RemsimaTM) intravenous therapy

Standard group

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 19-80 years
• Subjects diagnosed with perianal fistulizing Crohn's disease based on clinical, endoscopic, histological, and radiologic findings, etc.
• Subjects naive to both biological drugs (anti-TNFs, anti-integrin, anti-IL12/23, etc.) and investigational new drugs
• Subjects with at least one draining perianal fistula
• Subjects not responding to two or more conventional treatments (antibiotics, drainage, immunosuppressants, etc.)
• 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

You may not qualify if:

• In cases where written informed consents cannot be provided by the study subjects or the subjects' legally acceptable representative
• Subject with a probability of receiving bowel surgery within 12 weeks after baseline, decided by investigators
• Subjects with temporary or permanent stoma
• Subjects with short bowel syndrome
• Subjects not eligible due to significant bowel strictures or intra-abdominal abscesses
• 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
• Subjects with enterovaginal fistula, enterocutaneous fistula, or enteroenteric fistula
• Subjects previously exposed to biologics (anti-TNFs, anti-integrin, anti-IL12/23, etc.) or investigational new drugs
• Subjects with a history of hypersensitivity to monoclonal antibody
• 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)
• 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
• 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
• 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
• Subjects positive for anti-HCV antibody
• Subjects with a history of infection with HIV or subject positive for HIV Ag

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Related Publications (19)

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• Schwartz DA, Loftus EV Jr, Tremaine WJ, Panaccione R, Harmsen WS, Zinsmeister AR, Sandborn WJ. The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota. Gastroenterology. 2002 Apr;122(4):875-80. doi: 10.1053/gast.2002.32362.

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• Cheon JH, Kim YS, Ye BD, Lee KM, Kim YH, Kim JS, Han DS, Kim WH. Crohn's Disease Clinical Network and Cohort (CONNECT) Study: The First Step Toward Nationwide Multicenter Research of Crohn's Disease in Korea. Intest Res. 2014 Jul;12(3):173-5. doi: 10.5217/ir.2014.12.3.173. No abstract available.

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• Klag T, Goetz M, Stange EF, Wehkamp J. Medical Therapy of Perianal Crohn's Disease. Viszeralmedizin. 2015 Aug;31(4):265-72. doi: 10.1159/000434664. Epub 2015 Jul 29.

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• Park EJ, Song KH, Baik SH, Park JJ, Kang J, Lee KY, Goo JI, Kim NK. The efficacy of infliximab combined with surgical treatment of fistulizing perianal Crohn's disease: Comparative analysis according to fistula subtypes. Asian J Surg. 2018 Sep;41(5):438-447. doi: 10.1016/j.asjsur.2017.06.005. Epub 2017 Aug 26.

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  PMID: 14985485 BACKGROUND

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• Papamichael K, Rakowsky S, Rivera C, Cheifetz AS, Osterman MT. Association Between Serum Infliximab Trough Concentrations During Maintenance Therapy and Biochemical, Endoscopic, and Histologic Remission in Crohn's Disease. Inflamm Bowel Dis. 2018 Sep 15;24(10):2266-2271. doi: 10.1093/ibd/izy132.

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MeSH Terms

Conditions

Crohn Disease

Interventions

CT-P13

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Byong Duk Ye, MD, PhD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Byong Duk Ye, MD, PhD

CONTACT

82-2-3010-3181; bdye@amc.seoul.kr

Eun Ja Youn, RN

CONTACT

82-2-3010-8298; eunja.soul@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 10, 2023
• First Posted: September 22, 2023
• Study Start: November 1, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 14, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)