Stefan Schreiber1, Shomron Ben-Horin2, Jaroslaw Leszczyszyn3, Robert Dudkowiak4, Adi Lahat2, Beata Gawdis-Wojnarska5, Aldis Pukitis6, Marek Horynski7, Katalin Farkas8, Jaroslaw Kierkus9, Maciej Kowalski10, Sang Joon Lee11, Sung Hyun Kim12, Jee Hye Suh12, Mi Rim Kim12, Seul Gi Lee13, Byong Duk Ye14, Walter Reinisch15. 1. Department for Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany. 2. Gastroenterology Department, Chaim Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Hashomer, Israel. 3. Department of Gastroenterology, Melita Medical, Wroclaw, Poland. 4. Department of Gastroenterology, Melita Medical, Wroclaw, Poland; Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland. 5. Department of Gastroenterology, Twoja Przychodnia-Szczecińskie Centrum Medyczne, Szczecin, Poland. 6. Center of Gastroenterology, Hepatology and Nutrition, Pauls Stradins Clinical University Hospital, Riga, Latvia. 7. Endoskopia sp. z o.o., Sopot, Poland. 8. Department of Clinical Pharmacology, Szent Imre Egyetemi Oktatókórház, Budapest, Hungary. 9. Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland. 10. Gastroenterology Department, Centrum Diagnostyczno-Lecznicze Barska sp. z o.o., Wloclawek, Poland. 11. Clinical Development Division, Celltrion, Inc., Incheon, Republic of Korea. 12. Clinical Planning Department, Celltrion, Inc., Incheon, Republic of Korea. 13. Biometrics Department, Celltrion, Inc., Incheon, Republic of Korea. 14. Department of Gastroenterology and Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. Electronic address: bdye@amc.seoul.kr. 15. Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. Electronic address: walter.reinisch@meduniwien.ac.at.
Abstract
BACKGROUND & AIMS: This study compared pharmacokinetics, symptomatic and endoscopic efficacy, safety, and immunogenicity of a subcutaneous formulation of the infliximab biosimilar CT-P13 (CT-P13 SC) vs intravenous CT-P13 (CT-P13 IV) in patients with inflammatory bowel disease (IBD). METHODS: This randomized, multicenter, open-label, parallel-group, phase 1 study enrolled tumor necrosis factor inhibitor-naïve patients with active ulcerative colitis (total Mayo score 6-12 points with endoscopic subscore ≥2) or Crohn's disease (Crohn's Disease Activity Index 220-450 points) at 50 centers. After CT-P13 IV induction at Week (W) 0/W2, patients were randomized (1:1) to receive CT-P13 SC every 2 weeks (q2w) from W6 to W54 or CT-P13 IV every 8 weeks from W6 to W22. At W30, all patients receiving CT-P13 IV switched to CT-P13 SC q2w until W54. The primary endpoint was noninferiority of CT-P13 SC to CT-P13 IV for observed predose CT-P13 concentration at W22 (Ctrough,W22), concluded if the lower bound of the 2-sided 90% confidence interval (CI) for the ratio of geometric least-squares means exceeded 80%. RESULTS: Overall, 66 and 65 patients were randomized to CT-P13 SC and CT-P13 IV, respectively. The primary endpoint of noninferiority was met with a geometric least-squares means ratio for Ctrough,W22 of 1154.17% (90% CI 786.37-1694.00; n = 59 [CT-P13 SC]; n = 57 [CT-P13 IV]). W30/W54 clinical remission rates were comparable between arms. Other efficacy, safety, and immunogenicity assessments were also broadly comparable between arms, including after switching. CONCLUSIONS: The pharmacokinetic noninferiority of CT-P13 SC to CT-P13 IV, and the comparable efficacy, safety, and immunogenicity profiles, support the potential suitability of CT-P13 SC treatment in IBD. ClinicalTrials.gov ID: NCT02883452.
BACKGROUND & AIMS: This study compared pharmacokinetics, symptomatic and endoscopic efficacy, safety, and immunogenicity of a subcutaneous formulation of the infliximab biosimilar CT-P13 (CT-P13 SC) vs intravenous CT-P13 (CT-P13 IV) in patients with inflammatory bowel disease (IBD). METHODS: This randomized, multicenter, open-label, parallel-group, phase 1 study enrolled tumor necrosis factor inhibitor-naïve patients with active ulcerative colitis (total Mayo score 6-12 points with endoscopic subscore ≥2) or Crohn's disease (Crohn's Disease Activity Index 220-450 points) at 50 centers. After CT-P13 IV induction at Week (W) 0/W2, patients were randomized (1:1) to receive CT-P13 SC every 2 weeks (q2w) from W6 to W54 or CT-P13 IV every 8 weeks from W6 to W22. At W30, all patients receiving CT-P13 IV switched to CT-P13 SC q2w until W54. The primary endpoint was noninferiority of CT-P13 SC to CT-P13 IV for observed predose CT-P13 concentration at W22 (Ctrough,W22), concluded if the lower bound of the 2-sided 90% confidence interval (CI) for the ratio of geometric least-squares means exceeded 80%. RESULTS: Overall, 66 and 65 patients were randomized to CT-P13 SC and CT-P13 IV, respectively. The primary endpoint of noninferiority was met with a geometric least-squares means ratio for Ctrough,W22 of 1154.17% (90% CI 786.37-1694.00; n = 59 [CT-P13 SC]; n = 57 [CT-P13 IV]). W30/W54 clinical remission rates were comparable between arms. Other efficacy, safety, and immunogenicity assessments were also broadly comparable between arms, including after switching. CONCLUSIONS: The pharmacokinetic noninferiority of CT-P13 SC to CT-P13 IV, and the comparable efficacy, safety, and immunogenicity profiles, support the potential suitability of CT-P13 SC treatment in IBD. ClinicalTrials.gov ID: NCT02883452.
Authors: Aditi Kumar; Alexander Cole; Jonathan Segal; Philip Smith; Jimmy K Limdi Journal: Therap Adv Gastroenterol Date: 2022-02-17 Impact factor: 4.409
Authors: Jurij Hanzel; Laura H Bukkems; Krisztina B Gecse; Geert R D'Haens; Ron A A Mathôt Journal: Aliment Pharmacol Ther Date: 2021-09-24 Impact factor: 9.524