A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial: Multiple Independent Sub-studies of Setmelanotide in Patients with POMC/PCSK1, LEPR, NCOA1 (SRC1), or SH2B1 Gene Variants in the Melanocortin-4 Receptor Pathway
Our bodies rely on natural chemical signals to tell our brains when we are full. Some people have rare changes in specific genes, such as POMC, LEPR, or SH2B1, that disrupt these signals. This can lead to constant, intense hunger and severe weight gain that diet and exercise alone cannot fix. This Phase 3 clinical study is testing an injection medicine called setmelanotide (also known as IMCIVREE). Researchers are comparing it to a dummy treatment (placebo) to see if it helps adults manage their weight and curb severe hunger over 52 weeks. Half of the participants will receive the real medicine and half will receive the placebo. Doctors will track weight, waist size, hunger levels, and daily quality of life to see if setmelanotide is safe, effective, and well tolerated.
At a glance
What is this study about?
For most people, hunger is a simple message: your body needs food, and once you eat, the feeling fades. But for some individuals, the brain's hunger switch never quite turns off. This happens because of rare changes in certain genes that control how the body senses fullness. People with these genetic differences often feel extreme, unrelenting hunger and experience rapid, severe weight gain, regardless of how hard they try to diet.
This trial is looking at whether a medicine called setmelanotide can help restore that missing fullness signal. The drug works by copying a natural chemical messenger in the brain that tells you when you have eaten enough. By activating this pathway, doctors hope the medicine will help calm constant hunger and make it easier for people to reach a healthier weight.
Finding treatments that target the biological cause of this condition is vital. Severe obesity can cause joint pain, heart problems, and emotional distress. If successful, this research could offer a life-changing medical option for people whose weight issues are driven by their genetics, helping them gain better control over their health and quality of life.
Key takeaways
- Tests a daily injection medicine designed to reduce constant hunger and support weight loss.
- Aimed at adults aged 18 and older with specific, rare genetic changes affecting appetite signals.
- Involves a 52-week treatment period comparing the active drug against an inactive placebo.
- Requires regular clinic visits to monitor weight, waist measurements, and overall safety.
- Participation is entirely voluntary, and you can withdraw at any point.
Who may be eligible?
This trial is designed for adults aged 18 and older who have specific, confirmed changes in genes that control hunger and body weight (such as POMC, PCSK1, LEPR, NCOA1, or SH2B1). Both men and women can take part.
Because this study targets very specific genetic causes of weight gain, not everyone with weight challenges will be eligible. Participants will need to have genetic test results showing these exact variations, or be willing to undergo genetic testing as part of the screening process.
People with certain other serious health conditions or those taking specific medications that could interfere with the study drug may not be able to join. The study team will review each person's full medical history to make sure taking part is safe for them.
Could this study suit you?
Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.
- I am aged 18 or older.
- I experience constant, severe hunger and struggle with my body weight.
- I have had a genetic test (or am open to having one) for hunger-related genes like POMC, LEPR, or SH2B1.
- I am comfortable giving myself (or having someone give me) a daily injection under the skin.
- I can attend regular hospital or clinic appointments over a 52-week period.
What does participation involve?
Taking part in this study lasts for at least 52 weeks (about one year). Participants will be randomly chosen to receive either the study medicine (setmelanotide) or a placebo, which looks identical but contains no active drug. Neither you nor the study team will know which one you are receiving during the trial.
The medicine is given once a day as a small injection just under the skin, usually in the belly or thigh. You or a family member will be trained on how to do these injections at home. Throughout the year, you will need to attend regular clinic appointments for health checks.
At these visits, the study team will measure your weight, height, and waist size. They will take blood and urine samples and ask you to fill in questionnaires about your hunger levels, general wellbeing, and daily activities. The study team will closely monitor your progress and support you at every step.
Potential risks and benefits
Locations (5)
- —UnverifiedFrance
- —UnverifiedGermany
- —UnverifiedNetherlands
- —UnverifiedGreece
- —UnverifiedSpain
Common questions
What is a placebo?
A placebo is a dummy treatment that looks just like the real medicine but has no active ingredients. It helps scientists see if the changes seen are truly caused by the drug.
Will I have to pay for the treatment?
No. The study medicine, tests, and medical visits related to the trial are provided free of charge, and travel expenses are often covered.
How is the medicine given?
It is given as a daily injection just beneath the skin using a very fine needle, similar to how insulin is taken for diabetes.
Can I keep seeing my regular GP?
Yes. Your regular GP will be kept informed of your care, and you should continue to see them for any unrelated health concerns.
What happens if I want to stop?
You can leave the study whenever you choose. Your normal healthcare will continue as usual and your relationship with your doctors will not change.
How to find out more
Always speak to your GP or specialist before deciding to take part in a study.
Interested in taking part?
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