Efficacy and Safety of Formulation Switching Between SC Infliximab and IV Infliximab in Patients With CD

NCT06064864 | Recruiting

• 1 other identifier: 20220644
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this prospective, multicenter, open-label, randomized controlled, non-inferiority trial is to test efficacy and safety of formulation switching between subcutaneous (SC) infliximab and intravenous (IV) infliximab in patients with moderately to severely active Crohn's disease (CD). The primary endpoint of this study is deep remission at week 54. The main questions this study aims to answer are: Question-1) Is maintenance therapy with SC infliximab (120mg every 2 weeks) non-inferior to IV infliximab (5mg/kg every 8 weeks) in terms of deep remission at week 54? Question-2) Is maintenance therapy with SC infliximab (120mg every 2 weeks) non-inferior to IV infliximab (10mg/kg every 8 weeks) in terms of deep remission at week 54?

Conditions

Crohn's Disease

Keywords

Crohn's disease; Infliximab; Biosimilar; Remsima; Subcutaneous; Intravenous

Outcome Measures

Primary Outcomes (1)

• Deep remission rate of Arm 3 compared with Arm 2

  Deep remission: all of these 3 criteria (1) CDAI (Crohn's disease activity index) \<150, (2) SES-CD (Simple Endoscopic Score for Crohn's disease) ≤2, (3) No systemic corticosteroids use for at least 8 weeks before evaluation. CDAI can range from 0 to 600 and a higher value mean more clinically active disease. SES-CD is scored for 5 segments (ileum, right colon, transverse colon, left colon, and rectum) for (1) ulcer size, (2) % of ulcerated surface, (3) % of affected surface, and (4) the presence of stenosis. A higher value means a high endoscopic disease activity. The non-inferiority of Arm 3 compared with Arm 2 will be test and the non-inferiority margin will be set as "-20%".

  Week 54

Secondary Outcomes (9)

• Deep remission rate of Arm 3 compared with Arm 1

  Week 54

• Corticosteroid-free endoscopic remission rate of each arm

  Week 54

• Corticosteroid-free complete mucosal healing rate of each arm

  Week 54

• Corticosteroid-free clinical response (CDAI-70) rate of each arm

  Week 54

• Corticosteroid-free clinical response (CDAI-100) rate of each arm

  Week 54

Other Outcomes (2)

• Exploratory outcomes: trough level of infliximab to reach deep remission

  Week 30

• Exploratory outcomes: trough level of infliximab to reach clinical remission

  Week 30

Study Arms (3)

Non-response to SC infliximab at week 30 and switched to infliximab IV 10 mg/kg every 8 weeks

EXPERIMENTAL

Patients with moderately to severely active Crohn's disease will be given IV (intravenous) infliximab 5 mg/kg at week 0 and 2. Then, they will be treated with SC (subcutaneous) infliximab every 2 weeks from week 6. At week 30. patients will be allocated to one of 3 arms according to their response to SC infliximab. \[Arm 1\] Non-responders at week 30: Switched to infliximab IV 10 mg/kg every 8 weeks

Drug: Infliximab-Dyyb

Response to SC infliximab at week 30 and then, switched to infliximab IV 5 mg/kg every 8 weeks

EXPERIMENTAL

Patients with moderately to severely active Crohn's disease will be given IV (intravenous) infliximab 5 mg/kg at week 0 and 2. Then, they will be treated with SC (subcutaneous) infliximab every 2 weeks from week 6. At week 30. patients will be allocated to one of 3 arms according to their response to SC infliximab. \[Arm 2\] Response to SC infliximab at week 30 and then, randomly allocated to infliximab IV 5 mg/kg every 8 weeks

Drug: Infliximab-Dyyb

Response to SC infliximab at week 30 and then, continued infliximab SC 120 mg every 2 weeks

ACTIVE COMPARATOR

Patients with moderately to severely active Crohn's disease will be given IV (intravenous) infliximab 5 mg/kg at week 0 and 2. Then, they will be treated with SC (subcutaneous) infliximab every 2 weeks from week 6. At week 30. patients will be allocated to one of 3 arms according to their response to SC infliximab. \[Arm 3\] Response to SC infliximab at week 30 and then, randomly allocated to infliximab SC 120 mg every 2 weeks

Drug: Infliximab-Dyyb

Interventions

Infliximab-Dyyb DRUG

Continued infliximab SC 120 mg every other week, if response to SC infliximab at week 30

Also known as: Infliximab

Non-response to SC infliximab at week 30 and switched to infliximab IV 10 mg/kg every 8 weeks; Response to SC infliximab at week 30 and then, continued infliximab SC 120 mg every 2 weeks; Response to SC infliximab at week 30 and then, switched to infliximab IV 5 mg/kg every 8 weeks

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• Moderate to severe Crohn's disease (Crohn's disease activity index 220 to 450)
• Ileocolonic Crohn's disease (CD) with Simple Endoscopic Score for Crohn Disease ≥6 or ileal or colonic CD with with Simple Endoscopic Score for Crohn Disease ≥4 and ulcer score ≥1 in at least one segment
• Fecal calprotectin ≥250 µg/g or C-reactive protein≥0.5 mg/dL
• Patients who have never been to exposed to any biologic agent
• Patients who are non-responsive or intolerance to conventional therapy (corticosteroids, immunomodulators, or antibiotics, etc.) or contraindicated to conventional therapy
• Patients who gave a voluntary informed consent

You may not qualify if:

• Patients who have a history of hypersensitivity to humanized proteins
• Patients ever treated with corticosteroids within 8 weeks of screening date
• a) Symptomatic intestinal stricture, b) Symptomatic anal stricture, c) Untreated intra-abdominal abscess, d) Untreated perianal abscess, e) Abdominal surgery within 6 months, f) Patients who are expected to require intestinal surgeries during study period
• \- However, the following patients can be included: from baseline, 4 weeks or more after proper drainage of perianal abscess and from baseline, 8 weeks or more after proper drainage of intra-abdominal abscess
• Active tuberculosis. However, the following patients can be included: Patients who were diagnosed with tuberculosis, but were properly treated with anti-tuberculosis therapy according to the standard guidelines and who were confirmed to be cured.
• Latent tuberculosis infection (LTBI): Patients confirmed as having latent tuberculosis through medical history, physical examination, chest X-ray, PPD (Purified Protein Derivative) skin test or interferon gamma release assay (IGRA) by a pulmonology specialist. However, patients with LTBI who finished proper treatment for LTBI for 4 weks and who are going to complete LTBI treatment.
• HBsAg (Hepatitis B virus surface antigen)-positivity. Patients with negative HBsAg, but positive IgG anti-HBc (Immunoglobulin G anti-Hepatitis B core antibody) should be tested for HBV (hepatitis B virus) DNA real time quantitative PCR (polymerase chain reaction). If HBV DNA real time quantitative PCR ≥10 IU/mL should be excluded.
• Anti-HCV (hepatitis C virus) antibody-positivity
• History of HIV (human immunodeficiency virus) infection of positivity for anti-HIV
• Heart disease of NYHA (New York Heart Association) Class III/IV
• Active infection
• Malignancy (excluding skin basal cell carcinoma, skin squamous cell carcinoma, and uterine cervix cancer) or history of colonic or small bowel dysplasia within 5 years
• Pregnancy or lactating woman
• Patients who are not applying proper contraceptive measures and patients who do not have a plan for proper contraceptive measures for at least 6 months after the last dose of infliximab (oral, parenteral, or implantable hormonal contraceptives, diaphragm, condom, intra-uterine device, or abstinence are accepted as proper contraceptive methods.
• Patients who are decided to be not proper to be enrolled into the study by investigators.

Sponsors & Collaborators

• Asan Medical Center: lead
• Seoul National University Hospital: collaborator
• Severance Hospital: collaborator
• Kyung Hee University Hospital: collaborator
• Kyungpook National University Hospital: collaborator
• Samsung Medical Center: collaborator

Study Sites (1)

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Related Publications (3)

• Ye BD, Pesegova M, Alexeeva O, Osipenko M, Lahat A, Dorofeyev A, Fishman S, Levchenko O, Cheon JH, Scribano ML, Mateescu RB, Lee KM, Eun CS, Lee SJ, Lee SY, Kim H, Schreiber S, Fowler H, Cheung R, Kim YH. Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study. Lancet. 2019 Apr 27;393(10182):1699-1707. doi: 10.1016/S0140-6736(18)32196-2. Epub 2019 Mar 28.

  PMID: 30929895 BACKGROUND

• Schreiber S, Ben-Horin S, Leszczyszyn J, Dudkowiak R, Lahat A, Gawdis-Wojnarska B, Pukitis A, Horynski M, Farkas K, Kierkus J, Kowalski M, Lee SJ, Kim SH, Suh JH, Kim MR, Lee SG, Ye BD, Reinisch W. Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease. Gastroenterology. 2021 Jun;160(7):2340-2353. doi: 10.1053/j.gastro.2021.02.068. Epub 2021 Mar 5.

  PMID: 33676969 BACKGROUND

• Colombel JF, Rutgeerts PJ, Sandborn WJ, Yang M, Camez A, Pollack PF, Thakkar RB, Robinson AM, Chen N, Mulani PM, Chao J. Adalimumab induces deep remission in patients with Crohn's disease. Clin Gastroenterol Hepatol. 2014 Mar;12(3):414-22.e5. doi: 10.1016/j.cgh.2013.06.019. Epub 2013 Jul 12.

  PMID: 23856361 BACKGROUND

MeSH Terms

Conditions

Crohn Disease

Interventions

Infliximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: In this study, CD (Crohn's disease) patients who achieved clinical response at week 30 after to Remsima (CT-P13, a biosimilar of infliximab) SC (subcutaneous formulation) will be randomly (1:1) assigned to intravenous infliximab (Remsima) group (Arm 2) or to continued infliximab (Remsima) SC group (Arm 3). The primary endpoint of the study is the non-inferiority of Arm 3 compared with Arm 2 in terms of deep remission rate at week 54. Non-responder at week 30 will be allocated to Arm 1 (intravenous infliximab \[Remsima\] 10 mg/kg) and the secondary endpoint is the non-inferiority of Arm 3 compared with Arm 1 in terms of deep remission rate at week 54. Through this study, the investigators aim to provide the clinical evidence for selecting the most optimal formulation of infliximab according to therapeutic response among Korean patients with CD.

Study Record Dates

• First Submitted: September 10, 2023
• First Posted: October 3, 2023
• Study Start: October 9, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 14, 2024

Record last verified: 2024-05

Locations

KR (1)