Setmelanotide for Hypothalamic Obesity

Not currently recruiting at 35 trial locations

Overseen By Physician Inquiry Clinical Trials

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Rhythm Pharmaceuticals, Inc.

Disqualifiers: Prader-Willi, ROHHADNET, Severe psychiatric, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new drug, Setmelanotide, for reducing weight and hunger in people with hypothalamic obesity (HO), a condition often caused by brain injury affecting the hypothalamus. Participants will receive either Setmelanotide or a placebo (a substance with no active drug) through daily injections for one year. Individuals who have experienced significant weight gain due to hypothalamic injury and meet specific criteria, such as a high BMI (body mass index), may qualify. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on hormone replacement therapy, your dose must have been stable for at least 2 months before joining the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that setmelanotide has been tested for safety in people with hypothalamic obesity. In one study, most patients tolerated setmelanotide well, experiencing mild side effects like skin darkening and nausea, while serious side effects were rare. Another study found similar results, confirming that setmelanotide is safe for most people when used as directed. As this treatment is in a late-stage trial, extensive safety information is already available. However, discussing potential risks with a healthcare provider remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Hypothalamic Obesity?

Unlike the standard treatments for hypothalamic obesity, which often focus on lifestyle changes and medications targeting appetite suppression, Setmelanotide works differently by specifically targeting the melanocortin-4 receptor (MC4R) pathway. This pathway is crucial for regulating hunger and energy expenditure, making Setmelanotide a promising option for addressing the underlying cause of obesity in those with hypothalamic dysfunction. Researchers are excited about Setmelanotide because it offers a targeted approach that could potentially lead to more effective weight management for patients who struggle to see results with existing therapies.

What evidence suggests that Setmelanotide might be an effective treatment for Hypothalamic Obesity?

Research has shown that setmelanotide, which participants in this trial may receive, can aid weight loss in individuals with acquired hypothalamic obesity (HO). Studies have found that patients taking setmelanotide experienced significant reductions in their body mass index (BMI), a measure of body fat based on height and weight. Additionally, setmelanotide helps control hunger and improves overall quality of life for these patients. The treatment activates a pathway in the brain that regulates appetite and energy use. This promising evidence suggests that setmelanotide could be a helpful option for managing weight in people with HO. ^{1 2 3 6 7}

Who Is on the Research Team?

David Meeker, MD

Principal Investigator

Rhythm Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

This trial is for people aged 4 and older with acquired Hypothalamic Obesity, marked by weight gain after hypothalamic injury. Adults must have a BMI of ≥30 kg/m2, while children need a BMI in the top 95th percentile. Participants should agree to use effective contraception during and post-trial.

Inclusion Criteria

I have been diagnosed with hypothalamic obesity.

Agree to use a highly effective form of contraception throughout the study and for 90 days after the study

I am at least 4 years old.

Exclusion Criteria

I do not have severe mental health issues or thoughts of harming myself.

I or my close family have a history of skin cancer or melanoma.

I have lost more than 2% of my weight in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a daily injection of either setmelanotide or placebo for 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Setmelanotide

Trial Overview The study tests Setmelanotide's effectiveness on weight reduction, hunger control, and life quality in HO patients compared to placebo. It involves daily injections and assessments over up to 60 weeks.

How Is the Trial Designed?

Group I: Setemelanotide Experimental Treatment 1 Intervention

Randomized 2:1 (Setmelanotide: Placebo)

Group II: Placebo Placebo Group 1 Intervention

Randomized 2:1 (Setmelanotide: Placebo)

Setmelanotide is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Imcivree for:

• Chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS).

Approved in European Union as Imcivree for:

• Chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS).

Approved in Canada as Imcivree for:

• Chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS).

Who Is Running the Clinical Trial?

Rhythm Pharmaceuticals, Inc.

Lead Sponsor

Trials

31

Recruited

10,400+

Published Research Related to This Trial

Setmelanotide, a melanocortin-4 receptor agonist, led to significant weight loss of 30 kg (36% of body weight) in a 5-year-old child with obesity due to POMC deficiency after 12 months of treatment, demonstrating its efficacy in managing genetic obesity.

The treatment not only improved the child's hyperphagia and metabolic status but also positively impacted the quality of life for the parents, highlighting the broader benefits of early intervention with setmelanotide in young children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial Effects of Setmelanotide in a 5-Year-Old Boy With POMC Deficiency and on His Caregivers. Dubern, B., Lourdelle, A., Clément, K.[2023]

Setmelanotide is an FDA-approved injectable drug that significantly aids in weight loss, showing at least a 10% decrease in body weight after one year in patients with specific genetic forms of obesity, based on data from multiple clinical trials.

Common side effects include injection site reactions, skin hyperpigmentation, nausea, headache, and diarrhea, indicating that while effective, patients may experience notable adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Setmelanotide: A Novel Targeted Treatment for Monogenic Obesity. Pressley, H., Cornelio, CK., Adams, EN.[2023]

Setmelanotide is an MC4 receptor agonist approved in the USA for chronic weight management in patients aged 6 and older with obesity due to POMC, PCSK1, or LEPR deficiencies, highlighting its targeted efficacy for specific genetic causes of obesity.

The drug has also received PRIME designation from the European Medicines Agency, indicating its potential for treating obesity and hunger control in various rare genetic disorders linked to the MC4 receptor pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Setmelanotide: First Approval. Markham, A.[2021]

Setmelanotide, a melanocortin-4 receptor activator, has led to significant weight loss in two patients with pro-opiomelanocortin deficiency, a rare condition causing severe obesity.

While setmelanotide shows promise for treating obesity, caution is advised due to its potential effects on other melanocortin receptors, which could lead to unintended consequences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Precision Medicines: Curing POMC Deficiency. Müller, TD., Tschöp, MH., O'Rahilly, S.[2022]

Setmelanotide is a potent MC4R agonist that effectively promotes weight loss in obese individuals with MC4R deficiency, as demonstrated in a 28-day Phase 1b clinical trial.

The drug showed greater efficacy in patients with POMC defects compared to those with MC4R mutations, indicating that while Setmelanotide can aid weight loss in MC4R deficiency, further research is needed to determine its effectiveness across different genetic backgrounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency. Collet, TH., Dubern, B., Mokrosinski, J., et al.[2022]

Setmelanotide significantly aids in weight loss for patients with severe obesity linked to MC4R deficiency, with an average weight loss of 6.91% over a mean follow-up of 52 weeks among 328 patients.

While effective for weight loss, setmelanotide is associated with an increased risk of skin hyperpigmentation, indicating a need for monitoring side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Setmelanotide, a Melanocortin-4 Receptor Agonist, for Obese Patients: A Systematic Review and Meta-Analysis. Ferraz Barbosa, B., Aquino de Moraes, FC., Bordignon Barbosa, C., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04725240

Open-Label Study of Setmelanotide in Hypothalamic Obesity Documented increase in BMI (change from pre-surgery baseline in BMI z-score ≥0.2 for participants <18 years of age or BMI >5% for participants >18 years of age) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12544244/

OR11-01 Efficacy And Safety Of Setmelanotide In Acquired ... OR11-01 Efficacy And Safety Of Setmelanotide In Acquired Hypothalamic Obesity: Results ... We present results of an international Phase 3 trial ...

3. ir.rhythmtx.com ir.rhythmtx.com/news-releases/news-release-details/rhythm-pharmaceuticals-presents-data-mc4r-agonists-setmelanotide

Rhythm Pharmaceuticals Presents Data on MC4R Agonists ... Presentations highlight clinically meaningful reductions in BMI in patients with acquired hypothalamic obesity –. - Full data from Phase 3 ...

4. gastroenterologyadvisor.com gastroenterologyadvisor.com/news/setmelanotide-under-review-for-acquired-hypothalamic-obesity/

Setmelanotide Under Review for Acquired Hypothalamic ... The FDA has accepted the supplemental New Drug Application for setmelanotide in the treatment of acquired hypothalamic obesity.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05774756

A Trial of Setmelanotide in Acquired Hypothalamic Obesity The goal of this trial is to learn how well Setmelanotide works to improve weight reduction, hunger, and quality of life in patients 4 years of age and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38697184/

Setmelanotide for the treatment of acquired hypothalamic ... Interpretation: These findings support setmelanotide as a novel effective treatment of hypothalamic obesity. Funding: Rhythm Pharmaceuticals. 2024 Elsevier Ltd.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04725240

Open-Label Study of Setmelanotide in Hypothalamic Obesity The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.