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

Hypothalamic Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06239116
• Other study ID #: RM-718-001
• Status: Recruiting
• Phase: Phase 1
• Start date: March 5, 2024
• Est. completion date: June 30, 2025

Study information

• Verified date: March 2024
• Source: Rhythm Pharmaceuticals, Inc.
• Contact: Rhythm Clinical Trials
• Phone: (857) 264-4280
• Email: clinicaltrials[@]rhythmtx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 hypothalamic obesity (HO).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypothalamic Obesity
• Obesity

Intervention

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)
• 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)
• Part C: RM-718
Multiple ascending doses of RM-718 (specific to Part C dose cohorts)

Locations

Country	Name	City	State
United States	Worldwide Clinical Trials	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Rhythm Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	?z 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).
Secondary	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).
Secondary	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).
Secondary	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)