Evaluating RM-718 for treating hypothalamic obesity

A Study of RM-718 Weekly Formulation in Healthy Subjects With Obesity and in Patients With Obesity Due to MC4R Impairment

This study is testing a new drug called RM-718 to see if it can safely help people with hypothalamic obesity lose weight and improve their condition.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 12 Years to 65 Years
• Sex: All
• Sponsor: Rhythm Pharmaceuticals, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation
• Locations: 7 sites (Birmingham, Alabama and 6 other locations)
• Trial ID: NCT06239116 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety, tolerability, and pharmacokinetics of RM-718 in both healthy individuals with obesity and patients suffering from hypothalamic obesity (HO). The study is divided into three parts: the first two parts involve healthy subjects aged 18 to 55 receiving single and multiple ascending doses of RM-718 or placebo, while the third part focuses on patients aged 12 to 65 with HO receiving multiple doses of RM-718. The trial employs a double-blind, placebo-controlled design for the first two parts and an open-label approach for the third part, with doses administered weekly via subcutaneous injection.

Who should consider this trial

Good fit: Ideal candidates include healthy adults aged 18-55 with obesity or patients aged 12-65 with documented hypothalamic obesity.

Not a fit: Patients without hypothalamic obesity or those with other forms of obesity unrelated to hypothalamic dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with hypothalamic obesity, potentially improving their weight management and overall health.

How similar studies have performed: While this approach is novel in the context of hypothalamic obesity, similar studies targeting obesity through melanocortin receptor agonism have shown promise.

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.

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.

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.

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.
* 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.
* Pregnant and/or breastfeeding or desiring to become pregnant during this trial.

Other protocol defined Inclusion/Exclusion criteria may apply.

Where this trial is running

Birmingham, Alabama and 6 other locations

• UAB Pediatric Endocrinology (Part C and Part D) — Birmingham, Alabama, United States (Recruiting)
• Ann and Robert H. Lurie Children's Hospital of Chicago (Part C and Part D) — Chicago, Illinois, United States (Recruiting)
• Boston Children's Hospital (Part C only) — Boston, Massachusetts, United States (Recruiting)
• Brigham and Women's Hospital (Part C and Part D) — Boston, Massachusetts, United States (Recruiting)
• Vanderbilt University Medical Center (Part C only) — Nashville, Tennessee, United States (Recruiting)
• Worldwide Clinical Trials (Part A and Part B) — San Antonio, Texas, United States (Completed)
• University of Utah Pediatric Endocrine Clinic (Part C and Part D) — Salt Lake City, Utah, United States (Recruiting)

Study contacts

• Study coordinator: Rhythm Clinical Trials

Conditions Hypothalamic Obesity; Prader-Willi Syndrome; PWS; melanocortin 4 receptor; MC4R agonism; obesity