A Study of RM-718 in Healthy Subjects and Patients With MC4R Pathway Impairment

Prior treatment

• Cigarette smoking or dependence on caffeine, alcohol or drugs; unable or unwilling to abstain completely from caffeine, alcohol and related substances for 24 hours prior to and after study visits.
• Participation in any clinical trial with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first trial dose.
• Weight loss \>2% in the previous 3 months for patients aged ≥18 years or \>2% reduction in BMI for patients aged 12 to \<18 years and/or anti-obesity medications for the treatment of obesity.
• Bariatric surgery or procedure within the last 2 years.
• Participation in any clinical trial with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first trial dose, or previous use of setmelanotide.
• Obesity attributable to other genetic or syndromic conditions (eg, PPL \[pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), leptin receptor (LEPR), collectively\], Bardet-Biedl syndrome \[BBS\]) prior to the hypothalamic injury.
  • Part D
• Weight loss \>2% in the previous 3 months for patients aged ≥18 years or \>2% reduction in BMI for patients aged 12 to \<18 years or therapies for the treatment of obesity or hyperphagia.
• Metabolic and bariatric surgery (MBS) or procedure within last 6 months.
• Participation in any clinical trial with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first trial dose, or previous use of setmelanotide.
  • Other protocol defined Inclusion/Exclusion criteria may apply.

Other illness

• Active or history of any significant medical condition such as and including renal, hepatic, pulmonary, gastrointestinal, cardiovascular, genitourinary, endocrine, immunologic, metabolic, neurologic or hematological disease.
• History of renal transplant, end stage renal disease.
• Diagnosis of severe psychiatric disorders.
• Current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease considered severe enough to interfere with the trial and/or confound the results.
• History of recent surgery (within 60 days of Screening).
• Diagnosis of Prader-Willi syndrome (PWS) or Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor syndrome (ROHHADNET).
• Diagnosis of severe psychiatric disorders; any suicidal ideation, attempt or behavior.
• Current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease considered severe enough to interfere with the trial and/or confound the results.
• History of renal transplant, end stage renal disease.
• Diagnosis of severe psychiatric disorders; any suicidal ideation, attempt or behavior.
• Current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease considered severe enough to interfere with the trial and/or confound the results.

Other

• Parts A and B
• Any clinically significant abnormalities on screening laboratories or physical examination as determined by the Investigator.
• Obesity due to genetic, syndromic, or endocrine etiologies.
• Pregnant and/or breastfeeding or desiring to become pregnant during this trial.
  • Part C
• Pregnant and/or breastfeeding or desiring to become pregnant during this trial.
• Pregnant and/or breastfeeding or desiring to become pregnant during this trial.

• Parts A and B:
• Male and female subjects in good health aged 18-55 years of age at Screening.
• Body mass index (BMI) ≥30 kg/m2.
• Subjects who are medically healthy with normal or clinically insignificant screening results.
• Subjects must use a highly effective form of contraception and follow the study contraception requirements.
• Ability to communicate well with the Investigator, understand and comply with the requirements of the trial, and understand English and sign the written informed consent.
  • Part C:
• Male and female patients with HO, aged 12-65 years of age at Screening.
• Patient has documented evidence of acquired HO defined as:
  • Diagnosis of craniopharyngioma or other brain lesion affecting the hypothalamic region and has undergone surgery, or chemotherapy, or radiation therapy involving the hypothalamus at least 6 months before Screening, OR
  • Documented injury to the hypothalamus at least 6 months before Screening for which surgery/radiation is not indicated.
• Weight gain associated with the hypothalamic injury either before or following therapy (surgery and/or following chemotherapy or radiotherapy), and a BMI of ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th percentile for age and sex for patients 12 to \<18 years of age.
• Patients must use a highly effective form of contraception and follow the study contraception requirements.
• Ability to communicate with the Investigator, understand and comply with the requirements of the trial, and understand and sign the written informed consent and assent (for patients aged \<18 years), and informed consent for a parent or guardian of any patient \<18.
  • Part D:
• Confirmed diagnosis of PWS as determined by the Investigator at the time of Screening.
• Age ≥12 to 65, inclusive, at the time of signing Informed Consent and/or Assent.
• BMI ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th Percentile for age and sex for patients \<18 years of age based on the US CDC criteria.
• Able to meet contraception requirements.