A Study of RM-718 in Healthy Subjects and in Patients With HO
- Conditions
- Hypothalamic Obesity
- Registration Number
- NCT06239116
- Lead Sponsor
- Rhythm Pharmaceuticals, Inc.
- 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 hypothalamic obesity (HO).
- 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 16 weekly doses of open-label RM-718 in Part C. Study drug (RM-718 or placebo) doses are administered weekly via subcutaneous injection.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
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:
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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.
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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
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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). Area under the concentration versus time curve during a dosing interval
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). Maximum concentration measurement of RM-718 in plasma
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). Minimum plasma concentration of RM-718 reached during dosing interval
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). Time it takes for RM-718 to reach the maximum concentration (Cmax)
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). Time at which the lowest concentration value of RM-718 is observed
Ctrough 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). Observed pre-dose plasma concentration of RM-718
Cavg 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). Average concentration of RM-718 during a dosing interval in steady state
t1/2 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). Terminal elimination half-life of RM-718 in plasma
λz 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). Estimate of the terminal elimination rate constant of RM-718
CL/F 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). Clearance of RM-718 following extravascular administration
Vz/F 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). Volume of distribution of RM-718 following extravascular administration
Accumulation ratio of RM-718 Week 1 to Week 4 (AUC on Week 4/AUC on Week 1) (Parts B, C) Ratio of accumulation of RM-718 under steady state conditions
Change from baseline in BMI (Part C only) Baseline to Week 16 Mean change in weight (Part C only) Baseline to Week 16 Mean change in waist circumference (Part C only) Baseline to Week 16 Mean change in weekly average of the daily most hunger score in patients ≥12 years of age (Part C only) Baseline to Week 16 Mean change in weekly average of the Symptoms of Hyperphagia composite score (Part C only) Baseline to Week 16
Trial Locations
- Locations (7)
UAB Pediatric Endocrinology
🇺🇸Birmingham, Alabama, United States
Ann and Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Worldwide Clinical Trials
🇺🇸San Antonio, Texas, United States
University of Utah Pediatric Endocrine Clinic
🇺🇸Salt Lake City, Utah, United States