Dataset Information

Quality of life improvements following one year of setmelanotide in children and adult patients with Bardet-Biedl syndrome: phase 3 trial results.

ABSTRACT:

Background

Bardet-Biedl syndrome is a rare genetic disease associated with hyperphagia and early-onset, severe obesity. There is limited evidence on how hyperphagia and obesity affect health-related quality of life in patients with Bardet-Biedl syndrome, and on how management of these symptoms may influence disease burden. This analysis evaluated changes in health-related quality of life in adults and children with Bardet-Biedl syndrome in a Phase 3 trial following 1 year of setmelanotide treatment (ClinicalTrials.gov identifier: NCT03746522).

Methods

Patients with Bardet-Biedl syndrome and obesity received 52 weeks of treatment with setmelanotide and completed various self-reported health-related quality of life measures. Patients aged < 18 years or their caregiver completed the Pediatric Quality of Life Inventory (PedsQL; meaningful improvement, 4.4-point change); adults aged ≥ 18 years completed the Impact of Weight on Quality of Life Questionnaire-Lite (IWQOL-Lite; meaningful improvement range, 7.7-12-point change). Descriptive outcomes were reported in patients with data both at active treatment baseline and after 52 weeks of treatment.

Results

Twenty patients (< 18 years, n = 9; ≥ 18 years, n = 11) reported health-related quality of life at baseline and 52 weeks. For children and adolescents, PedsQL score mean change from baseline after 52 weeks was + 11.2; all patients with PedsQL impairment at baseline (n = 4) experienced clinically meaningful improvement. In adults, IWQOL-Lite score mean change from baseline was + 12.0. Of adults with IWQOL-Lite impairment at baseline (n = 8), 62.5% experienced clinically meaningful improvement. In adults, IWQOL-Lite score was significantly correlated with changes in percent body weight (P = 0.0037) and body mass index (P = 0.0098).

Conclusions

After 1 year of setmelanotide, patients reported clinically meaningful improvements across multiple health-related quality of life measures. This study highlights the need to address the impaired health-related quality of life in Bardet-Biedl syndrome, and supports utility of setmelanotide for reducing this burden. Trial Registration NCT03746522. Registered November 19, 2018, https://clinicaltrials.gov/ct2/show/NCT03746522 .

SUBMITTER: Forsythe E

PROVIDER: S-EPMC9841937 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Quality of life improvements following one year of setmelanotide in children and adult patients with Bardet-Biedl syndrome: phase 3 trial results.

Forsythe Elizabeth E Haws Robert M RM Argente Jesús J Beales Philip P Martos-Moreno Gabriel Á GÁ Dollfus Hélène H Chirila Costel C Gnanasakthy Ari A Buckley Brieana C BC Mallya Usha G UG Clément Karine K Haqq Andrea M AM

Orphanet journal of rare diseases 20230116 1

<h4>Background</h4>Bardet-Biedl syndrome is a rare genetic disease associated with hyperphagia and early-onset, severe obesity. There is limited evidence on how hyperphagia and obesity affect health-related quality of life in patients with Bardet-Biedl syndrome, and on how management of these symptoms may influence disease burden. This analysis evaluated changes in health-related quality of life in adults and children with Bardet-Biedl syndrome in a Phase 3 trial following 1 year of setmelanotid ...[more]

PMID: 36647077

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Project description:Abstract Objective Bardet-Biedl syndrome (BBS) is a rare genetic disease characterized by hyperphagia (pathologic insatiable hunger) and early-onset, severe obesity believed to be driven by impaired signaling in the melanocortin-4 receptor (MC4R) pathway. In a Phase 2 and a pivotal Phase 3 trial, treatment with the MC4R agonist setmelanotide produced beneficial reductions in weight, body mass index (BMI), BMI Z score, and hunger in patients with BBS at ∼1 year. The current analysis is the first to assess the continued long-term efficacy of setmelanotide administration in patients with BBS over ∼2 years. Methods Patients with BBS aged ≥6 years were eligible for this observational long-term extension (LTE) trial (NCT03651765) if they completed an index trial in which they received setmelanotide and demonstrated clinical benefit and acceptable safety as determined by the investigator. Patients received up to ∼12 months of setmelanotide as part of the index trial and began the LTE immediately following completion of the index trial. Study visits occurred approximately every 3 months in the LTE trial. Study objectives included evaluating changes in body weight and assessing safety and tolerability. The current analysis reports outcomes after ∼1 year of additional setmelanotide administration during the LTE trial, relative to index trial baseline. Results As of October 29, 2021, 54 patients with BBS enrolled the index trial, including 28 patients <18 years old and 26 patients ≥18 years old. Among patients who entered the LTE trial, 30 and 19 received at least 18 and 24 months of treatment, respectively. At their enrollment in their index trial, participants’ baseline mean (standard deviation [SD]) BMI was 42.2 (9.2) kg/m2, body weight in patients ≥18 years old was 132.3 (20.9) kg, and BMI Z score in patients <18 years old was 3.5 (0.76). Across age groups, after 18 and 24 months of treatment, mean (SD) percent change in BMI was −9.5% (10.5%; n=30) and −14.3% (11.6%; n=19), respectively. Mean (SD) percent change in body weight in those ≥18 years old after 18 and 24 months was −8.6% (10.3%; n=15) and −14.9% (10.4%; n=6), respectively. The mean (SD) change in BMI Z score in patients <18 years old after 18 and 24 months was −0.83 (0.50; n=13) and −0.72 (0.54; n=12), respectively. No new safety signals were observed during long-term setmelanotide administration. One patient discontinued because of an adverse event (hallucination; unlikely to be related to setmelanotide). Conclusions Clinically beneficial effects of setmelanotide on body weight-related measures continued to be observed in patients with BBS for up to 2 years. Only 1 patient discontinued the LTE trial due to an adverse event, suggesting setmelanotide continued to have clinical benefit and was generally well tolerated. These data support the long-term use of setmelanotide in patients with BBS. Presentation: No date and time listed

Project description:IntroductionBardet-Biedl syndrome (BBS) is a rare genetic disease associated with hyperphagia, a pathologic insatiable hunger, due to impaired signaling in the melanocortin-4 receptor (MC4R) pathway. The impact of hyperphagia on the lives of patients with BBS and their families has not been fully characterized.MethodsPatients with BBS or their caregivers who participated in clinical trials of the MC4R agonist setmelanotide (NCT03013543 and NCT03746522) were included in this qualitative study. Telephone interviews were conducted using a semistructured interview guide to explore patient experience and caregiver observations of hyperphagia before and during setmelanotide treatment.ResultsNineteen interviews (8 patients, 11 caregivers) were conducted. The term "hunger" (rather than "hyperphagia") was used in interviews to ensure common terminology. Before setmelanotide treatment, all participants described their (or their child's) hunger as all-consuming, leading to an obsessive focus on food. Nine participants recalled intense, continuous hunger, and most participants (5 patients, 10 caregivers) reported lack of control with eating. Negative impacts on patients' lives included difficulties with concentration, emotional and physical manifestations, and impaired relationships. All participants experienced or observed improvements in hunger and health outcomes during treatment, the most meaningful of which included weight loss and decrease in obsessive focus on food and food-seeking behaviors. All participants reported improvements in either physical and/or emotional well-being and being satisfied with setmelanotide.ConclusionsHyperphagia and resulting food-seeking behaviors have notable negative impacts on quality of life in patients with BBS and caregivers. Setmelanotide improved hyperphagia, reduced body weight and obsessive focus on food, and facilitated improvements in physical and emotional well-being for both patients and caregivers.Trial registrationNCT03013543 and NCT03746522.

Dataset Information

Quality of life improvements following one year of setmelanotide in children and adult patients with Bardet-Biedl syndrome: phase 3 trial results.

Background

Methods

Results

Conclusions

Publications

Quality of life improvements following one year of setmelanotide in children and adult patients with Bardet-Biedl syndrome: phase 3 trial results.

Similar Datasets

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