Study Design
proptosis
ADVERSE EVENTS, EVENTS, PROPTOSIS
The trial is a randomized, double-masked, placebo-controlled, parallel-group, multicenter, phase 4 trial, conducted at 11 sites in the United States. Patients were screened within 4 weeks prior to the Baseline Visit.The study comprised a 24-week masked period. Patients were randomized in a 2:1 ratio without stratification to receive 8 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) or placebo once every 3 weeks. Infusions were scheduled on Day 1 (baseline) and Weeks 3, 6, 9, 12, 15, 18, and 21 (with a final visit at Week 24) (Supplemental Figure S1 (A randomization schedule was performed by the contract research organization using the electronic data capture (EDC) system. The patients, investigators, trial site personnel (excluding the formulating pharmacists) and data assessors were masked to assigned treatment until study end.Unless there were infusion-associated events, the first 2 infusions of the double-masked periods were to be administered over 90 minutes, but not less than 80 minutes, and subsequent infusions over approximately 60 minutes but not less than 50 minutes. Patients were monitored for adverse events (AEs) during and for 60 minutes post infusion for the first 3 infusions, and for up to 30 minutes after subsequent infusions.At the end of the double-masked treatment period (Week 24), teprotumumab or placebo patients who were nonresponders (< 2-mm reduction in proptosis in the study eye) could enter an open-label period and receive 8 infusions of teprotumumab once every 3 weeks. Results from the masked period are reported here. The trial was approved by the U.S. Food and Drug Administration (FDA) and by the institutional review board or independent ethics committee at each trial site. The trial was conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. All patients provided written informed consent.Horizon Therapeutics sponsored the trial. All authors made the decision to submit the manuscript for publication.