Setmelanotide for Hypothalamic Obesity

Recruiting at 33 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

120 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Setmelanotide for treating hypothalamic obesity?

Setmelanotide has been shown to cause significant weight loss and reduce appetite in patients with genetic forms of obesity, such as those with POMC, PCSK1, and LEPR deficiencies. In clinical trials, patients experienced at least a 10% decrease in body weight after one year, and a case study reported a 36% weight loss in a child with POMC deficiency. ^{1 2 3 4 5}

Is setmelanotide safe for humans?

Setmelanotide has been tested in clinical trials and is generally considered safe, but common side effects include reactions at the injection site, skin darkening, nausea, headache, and diarrhea. In some cases, it may also cause temporary spontaneous erections. ^{1 2 3 6 7}

How is the drug setmelanotide unique for treating hypothalamic obesity?

Setmelanotide is unique because it targets the melanocortin-4 receptor, which is involved in regulating hunger and body weight, making it effective for genetic forms of obesity where this pathway is disrupted. It is administered as a daily injection and is the first FDA-approved drug for specific genetic obesity conditions, offering a novel approach compared to other treatments. ^{1 2 3 5 7}

What is the purpose of this trial?

This trial tests if Setmelanotide, an injection, can help reduce weight and hunger in patients aged 4 and older with acquired Hypothalamic Obesity. The medication works by targeting brain pathways that control hunger and energy use. Setmelanotide has been approved for treating obesity in rare genetic conditions and is being developed for other obesity-related disorders.

Research Team

David Meeker, MD

Principal Investigator

Rhythm Pharmaceuticals, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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, 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 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]

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, 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Setmelanotide: First Approval. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Setmelanotide: A Novel Targeted Treatment for Monogenic Obesity. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Beneficial Effects of Setmelanotide in a 5-Year-Old Boy With POMC Deficiency and on His Caregivers. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Setmelanotide, a Melanocortin-4 Receptor Agonist, for Obese Patients: A Systematic Review and Meta-Analysis. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subtype-4 receptor agonist. [2005]

7. United States pubmed.ncbi.nlm.nih.gov

Metabolic Precision Medicines: Curing POMC Deficiency. [2022]