A Study of RM-718 in Healthy Subjects and in Patients With HO

The purpose of this study is to evaluate the safety, tolerability, and PK of RM-718 in healthy subjects with obesity and in patients with hypothalamic obesity (HO).

This is a first-in-human and first-in-patient, 3-part study that includes the evaluation of safety, tolerability, and PK of: single ascending doses (SAD) of RM-718 weekly (RM-718) in healthy subjects 18 to 55 years of age with obesity (Part A), multiple ascending doses (MAD) of RM-718 in healthy subjects 18 to 55 years of age with obesity (Part B), and MAD of RM-718 in patients 12 to 65 years of age with HO (Part C). Cohorts in Parts A and B are double-blind, placebo-controlled, and randomized 2:1 (4 subjects receive RM-718, 2 subjects receive placebo). Part C evaluates open-label dose escalation in patients 12 to 65 years of age with HO. Study participants will receive: 1 weekly dose of either RM-718 or placebo in Part A, 4 weekly doses of either RM-718 or placebo in Part B, and 16 weekly doses of open-label RM-718 in Part C. Study drug (RM-718 or placebo) doses are administered weekly via subcutaneous injection.

Eligibility Criteria:
Key Inclusion Criteria:

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.

Key Exclusion Criteria:

Parts A and B

* Any clinically significant abnormalities on screening laboratories or physical examination as determined by the Investigator.
* 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.
* Obesity due to genetic, syndromic, or endocrine etiologies.
* 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.
* 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.
* History of recent surgery (within 60 days of Screening).
* 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.
* Pregnant and/or breastfeeding or desiring to become pregnant during this trial.

Part C

* Diagnosis of Prader-Willi syndrome (PWS) or Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor syndrome (ROHHADNET).
* 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.
* 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.
* 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 participation in a trial with setmelanotide.
* Pregnant and/or breastfeeding or desiring to become pregnant during this trial.
* 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.

Other protocol defined Inclusion/Exclusion criteria may apply.