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

A Study of RM-718 Weekly Formulation in Healthy Subjects With Obesity and in Patients With Hypothalamic Obesity (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).

Study Overview

• Status: Recruiting
• Conditions: Hypothalamic Obesity
• Intervention / Treatment: Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort); Drug: Part B: RM-718 or placebo (matched to specific RM-718 dose cohort); Drug: Part C: RM-718

Detailed Description

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 4 weekly doses of open-label RM-718 in Part C. Study drug (RM-718 or placebo) doses are administered weekly via subcutaneous injection.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Physician Inquiry Clinical Trials; Phone Number: (857) 264-4280; Email: clinicaltrials@rhythmtx.com
• Study Contact Backup: Name: Rhythm Clinical Trials; Phone Number: (857) 264-4280; Email: clinicaltrials@rhythmtx.com

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • Recruiting
      • Worldwide Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RM-718 (Cohort A1); Single dose of RM-718 (4) or placebo (2)	Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort); Single ascending dose of RM-718 or placebo (matched to specific RM-718 Part A dose cohort)
Experimental: RM-718 (Cohort A2); Single dose of RM-718 (4) or placebo (2)	Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort); Single ascending dose of RM-718 or placebo (matched to specific RM-718 Part A dose cohort)
Experimental: RM-718 (Cohort A3); Single dose of RM-718 (4) or placebo (2)	Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort); Single ascending dose of RM-718 or placebo (matched to specific RM-718 Part A dose cohort)
Experimental: RM-718 (Cohort A4); Single dose of RM-718 (4) or placebo (2)	Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort); Single ascending dose of RM-718 or placebo (matched to specific RM-718 Part A dose cohort)
Experimental: RM-718 (Cohort A5); Single dose of RM-718 (4) or placebo (2)	Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort); Single ascending dose of RM-718 or placebo (matched to specific RM-718 Part A dose cohort)
Experimental: RM-718 (Cohort A6); Single dose of RM-718 (4) or placebo (2)	Drug: Part A: RM-718 or placebo (matched to specific RM-718 dose cohort); Single ascending dose of RM-718 or placebo (matched to specific RM-718 Part A dose cohort)
Experimental: RM-718 (Cohort B1); Multiple doses of RM-718 (4) or placebo (2)	Drug: Part B: RM-718 or placebo (matched to specific RM-718 dose cohort); Multiple ascending doses of RM-718 or placebo (matched to specific RM-718 Part B dose cohorts)
Experimental: RM-718 (Cohort B2); Multiple ascending doses of RM-718 (4) or placebo (2)	Drug: Part B: RM-718 or placebo (matched to specific RM-718 dose cohort); Multiple ascending doses of RM-718 or placebo (matched to specific RM-718 Part B dose cohorts)
Experimental: RM-718 (Cohort B3); Multiple ascending doses of RM-718 (4) or placebo (2)	Drug: Part B: RM-718 or placebo (matched to specific RM-718 dose cohort); Multiple ascending doses of RM-718 or placebo (matched to specific RM-718 Part B dose cohorts)
Experimental: RM-718 (Cohort B4); Multiple ascending doses of RM-718 (4) or placebo (2)	Drug: Part B: RM-718 or placebo (matched to specific RM-718 dose cohort); Multiple ascending doses of RM-718 or placebo (matched to specific RM-718 Part B dose cohorts)
Experimental: RM-718 (Cohort B5); Multiple ascending doses of RM-718 (4) or placebo (2)	Drug: Part B: RM-718 or placebo (matched to specific RM-718 dose cohort); Multiple ascending doses of RM-718 or placebo (matched to specific RM-718 Part B dose cohorts)
Experimental: RM-718 (Cohort C1); Multiple ascending doses of RM-718 (8)	Drug: Part C: RM-718; Multiple ascending doses of RM-718 (specific to Part C dose cohorts)
Experimental: RM-718 (Cohort C2); Multiple ascending doses of RM-718 (8)	Drug: Part C: RM-718; Multiple ascending doses of RM-718 (specific to Part C dose cohorts)
Experimental: RM-718 (Cohort C3); Multiple ascending doses of RM-718 (8)	Drug: Part C: RM-718; Multiple ascending doses of RM-718 (specific to Part C dose cohorts)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Parts A, B, C: 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 and Part C cohorts)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCtau measurement of RM-718	Area under the concentration versus time curve during a dosing interval	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	Maximum concentration measurement of RM-718 in plasma	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	Minimum plasma concentration of RM-718 reached during dosing interval	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	Time it takes for RM-718 to reach the maximum concentration (Cmax)	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	Time at which the lowest concentration value of RM-718 is observed	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).
Ctrough measurement of RM-718	Observed pre-dose plasma concentration 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).
Cavg measurement of RM-718	Average concentration of RM-718 during a dosing interval in steady state	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).
t1/2 measurement of RM-718	Terminal elimination half-life of RM-718 in plasma	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).
λz measurement of RM-718	Estimate of the terminal elimination rate constant 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).
CL/F measurement of RM-718	Clearance of RM-718 following extravascular administration	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).
Vz/F measurement of RM-718	Volume of distribution of RM-718 following extravascular administration	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).
Accumulation ratio of RM-718	Ratio of accumulation of RM-718 under steady state conditions	Week 1 to Week 4 (AUC on Week 4/AUC on Week 1) (Parts B, C)

Collaborators and Investigators

• Sponsor: Rhythm Pharmaceuticals, Inc.
• Investigators: Study Chair: David Meeker, Rhythm Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: January 25, 2024
• First Submitted That Met QC Criteria: January 25, 2024
• First Posted (Actual): February 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: obesity; melanocortin 4 receptor (MC4R); MC4R agonism
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: RM-718-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes