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

NCT06239116 | Recruiting Phase 1 FDA Drug

• 1 other identifier: RM-718-001
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 7

Brief Summary

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 MC4R Pathway Impairment

Conditions

Hypothalamic Obesity; Prader-Willi Syndrome; PWS

Keywords

melanocortin 4 receptor (MC4R); MC4R agonism; obesity

Outcome Measures

Primary Outcomes (1)

• Parts A, B, C, D: Safety and Tolerability Assessed by Number of Study Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  From Day 1 through the Safety-Follow-up call (up to Day 43 for all Part A cohorts, up to Day 70 for all Part B cohorts, up to Day 140 for Part C cohort, up to Day 210 for Part D cohort)

Secondary Outcomes (24)

• AUCtau measurement of RM-718

  up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).

• Cmax measurement of RM-718

  up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).

• Cmin measurement of RM-718

  up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).

• Tmax measurement of RM-718

  up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).

• Tmin measurement of RM-718

  up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).

Study Arms (17)

RM-718 (Cohort A1)

EXPERIMENTAL

Single dose of RM-718 (4) or placebo (2)

Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort A2)

EXPERIMENTAL

Single dose of RM-718 (4) or placebo (2)

Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort A3)

EXPERIMENTAL

Single dose of RM-718 (4) or placebo (2)

Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort A4)

EXPERIMENTAL

Single dose of RM-718 (4) or placebo (2)

Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort A5)

EXPERIMENTAL

Single dose of RM-718 (4) or placebo (2)

Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort A6)

EXPERIMENTAL

Single dose of RM-718 (4) or placebo (2)

Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort A7)

EXPERIMENTAL

Single dose of RM-718 (4) or placebo (2)

Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort A8)

EXPERIMENTAL

Single dose of RM-718 (4) or placebo (2)

Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort A9)

EXPERIMENTAL

Single dose of RM-718 (4) or placebo (2)

Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort B1)

EXPERIMENTAL

Multiple ascending doses of RM-718 (4) or placebo (2)

Drug: Part B: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort B2)

EXPERIMENTAL

Multiple ascending doses of RM-718 (4) or placebo (2)

Drug: Part B: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort B3)

EXPERIMENTAL

Multiple ascending doses of RM-718 (4) or placebo (2)

Drug: Part B: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort B4)

EXPERIMENTAL

Multiple ascending doses of RM-718 (4) or placebo (2)

Drug: Part B: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort B5)

EXPERIMENTAL

Multiple ascending doses of RM-718 (4) or placebo (2)

Drug: Part B: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort B6)

EXPERIMENTAL

Multiple ascending doses of RM-718 (4) or placebo (2)

Drug: Part B: RM-718 or placebo (matched to specific RM-718 dose cohort)

RM-718 (Cohort C1)

EXPERIMENTAL

Multiple ascending doses of RM-718 (30)

Drug: Part C: RM-718

RM-718 (Cohort D1)

EXPERIMENTAL

Multiple ascending doses of RM-718 (up to 30)

Drug: Part D: RM-718

Interventions

Part B: RM-718 or placebo (matched to specific RM-718 dose cohort) DRUG

Multiple ascending doses of RM-718 or placebo (matched to specific RM-718 Part B dose cohorts)

RM-718 (Cohort B1); RM-718 (Cohort B2); RM-718 (Cohort B3); RM-718 (Cohort B4); RM-718 (Cohort B5); RM-718 (Cohort B6)

Part C: RM-718 DRUG

Multiple ascending doses of RM-718

RM-718 (Cohort C1)

Part D: RM-718 DRUG

Multiple ascending doses of RM-718

RM-718 (Cohort D1)

Part A: RM-718 or placebo (matched to specific RM-718 dose cohort) DRUG

Single ascending dose of RM-718 or placebo (matched to specific RM-718 Part A dose cohort)

RM-718 (Cohort A1); RM-718 (Cohort A2); RM-718 (Cohort A3); RM-718 (Cohort A4); RM-718 (Cohort A5); RM-718 (Cohort A6); RM-718 (Cohort A7); RM-718 (Cohort A8); RM-718 (Cohort A9)

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rhythm Pharmaceuticals, Inc.: lead

Study Sites (7)

UAB Pediatric Endocrinology (Part C and Part D)

Birmingham, Alabama, 35233, United States

RECRUITING

Ann and Robert H. Lurie Children's Hospital of Chicago (Part C and Part D)

Chicago, Illinois, 60611, United States

RECRUITING

Boston Children's Hospital (Part C only)

Boston, Massachusetts, 021115, United States

RECRUITING

Brigham and Women's Hospital (Part C and Part D)

Boston, Massachusetts, 02115, United States

RECRUITING

Vanderbilt University Medical Center (Part C only)

Nashville, Tennessee, 37232, United States

RECRUITING

Worldwide Clinical Trials (Part A and Part B)

San Antonio, Texas, 78217, United States

COMPLETED

University of Utah Pediatric Endocrine Clinic (Part C and Part D)

Salt Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Conditions

Sexual Infantilism; Prader-Willi Syndrome; Obesity

Condition Hierarchy (Ancestors)

Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• David Meeker

  Rhythm Pharmaceuticals, Inc.

  STUDY CHAIR

Central Study Contacts

Rhythm Clinical Trials

CONTACT

(857) 264-4280; clinicaltrials@rhythmtx.com

Physician Inquiry Clinical Trials

CONTACT

(857) 264-4280; clinicaltrials@rhythmtx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Study Parts A and B are blinded. Study Parts C and D are open-label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2024
• First Posted: February 2, 2024
• Study Start: March 5, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)