Study design
SBS-IF, Crohn’s disease, SBS
STERILE, REMISSION
Two open-label, multicenter phase III clinical trials of teduglutide in adult patients with SBS-IF and their extension study were conducted in Japan: TED-C14-004 (ClinicalTrials.gov identifier NCT02340819) involved short-term (24 weeks) and long-term (up to 30 months) treatment with teduglutide; SHP633-306 (ClinicalTrials.gov identifier NCT03663582) involved only short-term (24 weeks) treatment with teduglutide; and SHP633-307 (ClinicalTrials.gov identifier NCT03596164) was a long-term extension study that enrolled patients who completed TED-C14-004 or SHP633-306.TED-C14-004 was conducted between December 2014 and November 2018, and SHP633-306 was conducted between July 2018 and August 2019. SHP633-307 is ongoing at the time of this analysis, so February 2020 was used as the interim data cut-off point. The studies were conducted in accordance with the principles of the World Medical Association Declaration of Helsinki and applicable laws and standards of good clinical practice in Japan. Upon approval of the study protocol from institutional review boards or ethics committees, written informed consent from patients was obtained prior to their involvement in any study activities. The inclusion and exclusion criteria, dose of teduglutide, and treatment duration used for studies TED-C14-004 and SHP633-306 were based on those used in the pivotal multinational STEPS-1 study [Patients who entered TED-C14-004 or SHP633-306 had to be ≥ 16 years old, have SBS as a result of major intestinal resection, and have been dependent on PS ≥ 3 times per week for ≥ 12 months before enrollment, with a < 10% change in weekly PS volume for ≥ 4 consecutive weeks before the start of treatment with teduglutide. Patients with a history of Crohn’s disease could participate if they had been in clinical remission (inactive Crohn’s disease demonstrated by clinical assessment) for ≥ 12 weeks before teduglutide dosing. Key exclusion criteria included use of native GLP-2 or human growth hormone in the 6 months before study start or any prior use of teduglutide. To be eligible for SHP633-307, patients had to have completed SHP633-306 or had ongoing participation in TED-C14-004 at the time of study closure.An overview of the study designs for TED-C14-004, SHP633-306, and SHP633-307 is given in Fig. In TED-C14-004, there was no training for patients or caregivers on how to administer teduglutide at home. However, for SHP633-306 and SHP633-307, patients or caregivers were provided a detailed training manual and a quick reference guide. The first dose was administered by a study physician, who then observed the patient or caregiver administering teduglutide at least twice in compliance with an administration checklist prior to patients or caregivers administering the drug unsupervised. To ensure teduglutide continued to be administered correctly and safely at home, the study physician supervised administration at select study visits during the treatment period. To facilitate the preparation and administration of teduglutide, a vial adaptor was also implemented in SHP633-306 and SHP633-307 for reconstitution of lyophilized teduglutide with sterile water for injection and drawing of the reconstituted drug into a dosing syringe with a safety lock.Study design of TED-C14-004, SHP633-306