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)
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).
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. |
Country | Name | City | State |
---|---|---|---|
United States | Worldwide Clinical Trials | San Antonio | Texas |
Lead Sponsor | Collaborator |
---|---|
Rhythm Pharmaceuticals, Inc. |
United States,
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) |
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