What side effects are associated with this type of intervention?

Common treatments for obesity include lifestyle interventions, pharmacotherapy, and bariatric surgery. Pharmacotherapy options such as GLP-1 receptor agonists (e.g., semaglutide) can cause gastrointestinal side effects like nausea, vomiting, and diarrhea. MC4R agonists like Setmelanotide, currently under investigation, may have side effects including injection site reactions, hyperpigmentation, and gastrointestinal issues. Other anti-obesity medications, such as orlistat, can cause gastrointestinal discomfort and steatorrhea. Phentermine-topiramate may lead to increased heart rate, insomnia, and mood changes. It is important to discuss these potential side effects with a healthcare provider to determine the most appropriate treatment.

What prior FDA approvals exist?

The FDA has approved several medications for the treatment of obesity, including phentermine-topiramate, liraglutide, and orlistat. These drugs work through various mechanisms such as appetite suppression and inhibition of fat absorption. Setmelanotide, an MC4R agonist, is being studied for its potential in treating obesity related to specific genetic variants in the melanocortin-4 receptor pathway. While Setmelanotide is still under investigation, it represents a targeted approach that differs from the broader mechanisms of currently approved treatments.

What other types of research exist?

Promising novel alternatives to Setmelanotide for obesity treatment in 2024 include GLP-1 receptor agonists such as semaglutide and tirzepatide, which have shown significant weight loss in clinical trials. Additionally, combination therapies like GLP-1 receptor agonists with SGLT2 inhibitors are being explored for enhanced efficacy in weight management.

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Melanocortin-4 Receptor Agonist

Setmelanotide for Obesity

Phase 2

Waitlist Available

Research Sponsored by Rhythm Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have a pre-identified genetic variant in an established MC4R pathway gene that contributes to obesity

Age 6 to 65 years, inclusive

Must not have

Patients previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide

Patients with the following genetic variants: biallelic Bardet-Biedl Syndrome (BBS); biallelic Alström Syndrome 1 (ALMS1); homozygous, heterozygous, or compound heterozygous variants in MC4R, POMC, PCSK1, LEPR, nuclear receptor coactivator 1 (NCOA1; steroid receptor coactivator-1 [SRC1]) or SRC homology 2 B adapter protein 1 (SH2B1) genes as well as 16p11.2 chromosomal deletions that include the SH2B1 gene

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, week 16

Summary

This trial tests setmelanotide, a medication to help control weight, in obese patients with specific genetic defects. These patients have issues that make typical treatments less effective. Setmelanotide helps reduce hunger and increase energy use. It has been approved in the USA for weight management.

Who is the study for?

This trial is for people aged 6-65 with severe obesity linked to specific genetic changes in the MC4R pathway. Participants must understand the study, use effective birth control, and have a BMI ≥40 kg/m2 (adults) or ≥97th percentile for their age/gender (children). Excluded are those with certain other genetic conditions, recent bariatric surgery, significant health issues like liver disease or melanoma risk, psychiatric disorders, or recent weight loss treatments.

What is being tested?

The DAYBREAK study tests Setmelanotide's effectiveness on obesity due to MC4R pathway gene variants. It starts with an open-label phase where everyone gets Setmelanotide followed by a blind phase where participants randomly receive either Setmelanotide or a placebo without knowing which one they're getting.

What are the potential side effects?

While not specified here, potential side effects of Setmelanotide may include reactions at the injection site, increased pigmentation of skin or hair, nausea and possibly others based on its action in regulating appetite and energy expenditure.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a genetic variant linked to obesity.

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I am between 6 and 65 years old.

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I often feel an uncontrollable urge to eat.

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I am considered obese based on my BMI.

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I (or my guardian) understand the study and can consent.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have never participated in a study or taken setmelanotide before.

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I have specific genetic conditions related to obesity.

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I or my close family have had melanoma, or I have a history of albinism.

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I have serious skin changes related to melanoma or almost-melanoma.

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I do not have severe lung, heart, or cancer-related health issues that could affect the study.

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I have a history of serious liver disease.

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My kidney function is low, with a GFR under 30 mL/min.

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I have a genetic condition linked to obesity.

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I am currently breastfeeding.

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I've lost more than 2% of my weight in the last 3 months due to diet, exercise, or weight loss supplements.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, week 16

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, week 16

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, week 16 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1

Secondary study objectives

Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype

Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype

Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype

+6 more

Side effects data

From 2022 Phase 4 trial • 77 Patients • NCT05046132

46%

Nausea

39%

Injection site pain

29%

Vomiting

25%

Injection site erythema

21%

Ephelides

21%

Decreased appetite

18%

Skin hyperpigmentation

14%

Injection site swelling

14%

Headache

14%

Erection increased

11%

Injection site pruritus

11%

Fatigue

Abdominal pain

Constipation

Pancreatitis acute

Hepatitis acute

Asthenia

Chills

Injection site induration

Medical device site dermatitis

Aphthous ulcer

Change of bowel habit

Chapped lips

Diarrhoea

Gingival discolouration

Hyperaesthesia teeth

Pruritus

Rash

Cough

Dry throat

Dyspnoea

Rhinorrhoea

Muscle spasms

Pain in extremity

Palpitations

Skin abrasion

Blood creatine phosphokinase increased

Abnormal dreams

100%

80%

60%

40%

20%

Study treatment Arm

Group 1: Setmelanotide 2 mg

Group 1: Setmelanotide 3 mg

Group 2: Moxifloxacin 400mg

Group 1: Setmelanotide 5 mg

Group 1: Setmelanotide 7 mg

Group 2: Placebo

Group 3: Placebo

Group 3: Moxifloxacin 400mg

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Stage 2: Setmelanotide (Double-Blind)Experimental Treatment1 Intervention

Participants from Stage 1 who were eligible for Stage 2 received once daily SC injection of setmelanotide 3.0 mg from Week 16 to Week 40 in a double-blind treatment Stage (Stage 2).

Group II: Stage 1: Setmelanotide (Open-Label)Experimental Treatment1 Intervention

Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 milligrams (mg) once daily for approximately 2 weeks, then increased to 3.0 mg once daily. Participants \<12 years of age started on setmelanotide 1.0 mg once daily for approximately 1 week, then increased to 2.0 mg once daily for approximately 1 week, then increased to 3.0 mg once daily.

Group III: Stage 2: Placebo (Double-Blind)Placebo Group1 Intervention

Participants from Stage 1 who were eligible for Stage 2 received once daily SC injection of matching placebo 3.0 mg from Week 16 to Week 40 in a double-blind treatment Stage (Stage 2).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Setmelanotide

2017

Completed Phase 4

~800

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for obesity include lifestyle interventions, pharmacotherapy, and bariatric surgery. Lifestyle interventions focus on diet and exercise to create a calorie deficit. Pharmacotherapy includes drugs like orlistat, which inhibits fat absorption, and GLP-1 agonists like semaglutide, which enhance satiety and reduce appetite. Setmelanotide, an MC4R agonist, works by activating the melanocortin-4 receptor pathway, which plays a crucial role in regulating hunger and energy expenditure. This is particularly important for obesity patients with specific genetic mutations affecting this pathway, as it directly addresses the underlying cause of their weight gain, offering a more targeted and potentially effective treatment option.