Trial design
fasting TG, TG, SHTG, T2DM
HYPERTENSION, POLAND
The ENTRIGUE trial was a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 trial designed to assess the efficacy, safety, and tolerability of pegozafermin administered subcutaneously QW or Q2W in participants with SHTG. Participants with screening fasting TG ≥ 500 mg dlParticipants were enrolled into one of the following two cohorts: (1) main study cohort (could not be on concurrent fibrate therapy) or (2) fibrate expansion cohort. The fibrate expansion cohort was initiated as a protocol amendment (v2.0) after the start of the study to evaluate pegozafermin in participants on stable fibrate therapy, as these medications are commonly used to treat SHTG. The main study cohort was randomized 1:1:1:1:1 to one of the four doses of pegozafermin (9 mg QW, 18 mg QW, 27 mg QW or 36 mg Q2W) or placebo, and the fibrate cohort was randomized 1:1 to either pegozafermin 27 mg QW or placebo QW for 8 weeks (Extended Data Fig. Participants were required to fast for 12–14 h and abstain from alcohol for 48 h before each lipid assessment throughout the study. Following a lifestyle stabilization period (4 weeks if on stable approved LMT; up to 6 weeks if washing out ineligible LMT), a ~2-week qualification period occurred consisting of two fasting TG assessments at least 1 week apart. If mean TG levels from these two laboratory evaluations were not within the inclusion range, an additional third assessment was collected at least 1 week apart from the previous assessment. The mean TG value from the last two assessments served as TG qualification for the study and was the basis for participant TG stratification at randomization. Exclusion criteria included uncontrolled or recent diagnosis of hypertension, uncontrolled or recent diagnosis of T2DM within 6 months of screening, HbA1c ≥ 9.5%, BMI > 45 kg mThe trial was conducted at 50 clinical sites in the United States, Hungary, Poland and the Czech Republic from September 2020 to June 2022 (