IntroductionAcquired hypothalamic obesity (HO), caused by hypothalamic injury, is characterized by hyperphagia (i.e., insatiable hunger and abnormal food-seeking behaviors), reduced energy expenditure, and accelerated and sustained weight gain, all of which substantially impact quality of life. In the Phase 3, randomized, double-blind, placebo-controlled TRANSCEND trial (ClinicalTrials.gov identifier: NCT05774756), setmelanotide demonstrated significant improvements compared with placebo in body mass index, hunger, symptoms of hyperphagia, and quality of life in participants with acquired HO. This substudy further characterizes changes in hunger, weight, energy level, and physical activity with setmelanotide and assesses the perceived meaningfulness of such benefits to patients and their caregivers.MethodsIn-depth, 75-min qualitative interviews were conducted from July 2024 to January 2025 with eligible and consented English-speaking TRANSCEND trial participants or their caregivers in the United States. Interviews followed a semistructured interview guide tailored to facilitate discussion about participant experiences or caregiver observations regarding changes in weight, hunger, and energy level before and during trial participation. Interview participants were also asked to describe the perceived meaningfulness of any changes experienced. Interviews were audio recorded and transcribed; thematic analysis was conducted using ATLAS.ti (https://atlasti.com/).ResultsOf the 30 interview participants, 14 were trial participants (4 adolescents and 10 adults) and 16 were caregivers of participants aged n = 8) and ≥ 12 years (n = 8); 23 received setmelanotide and 7 received placebo. All interview participants reported insatiable hunger and accelerated and sustained weight gain after hypothalamic injury but before starting the trial; 29 of 30 interview participants reported reduced energy level. Consistently, trial participants who received setmelanotide and their caregivers reported beneficial changes in hunger, weight, energy level, and physical activity, and indicated these changes were meaningful, while in placebo-treated participants, no such changes were observed.ConclusionThese findings support the Phase 3 TRANSCEND efficacy outcomes pertaining to weight, hunger, energy levels, and quality of life and that the impactful changes with setmelanotide in patients with acquired HO and their caregivers extend beyond body mass index and weight reduction.Clinical trial registrationClinicalTrials.gov, identifier NCT05774756.
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