RM-718 for Hypothalamic Obesity

Recruiting at 5 trial locations

Overseen By Physician Inquiry Clinical Trials

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Rhythm Pharmaceuticals, Inc.

Must not be taking: Anti-obesity medications

Disqualifiers: Severe psychiatric disorders, Renal disease, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 21

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, RM-718, to determine its safety and tolerability for individuals with obesity, including those with hypothalamic obesity (weight gain due to damage to a specific brain area). The study will assess how the body processes RM-718 and compare different doses to identify the optimal one. Suitable participants include generally healthy individuals with a body mass index (BMI) of 30 or higher, or those with hypothalamic obesity following a brain injury or treatment affecting that area. As a Phase 1 trial, this research aims to understand how RM-718 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial investigators to understand any specific requirements.

Is there any evidence suggesting that RM-718 is likely to be safe for humans?

Research shows that RM-718 is being tested for safety and tolerability, particularly for obesity linked to the brain's hypothalamus. Earlier studies found that RM-718 did not cause unexpected side effects on the heart and blood vessels, which is promising. This suggests it likely does not lead to issues like high blood pressure or heart problems, common concerns with weight-loss treatments.

The drug is currently in early trials, tested in small groups to assess safety. This phase is crucial to ensure the drug's safety before larger trials. Although detailed safety information is limited, these early tests aim to identify any major safety issues before proceeding. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypothalamic obesity?

Unlike the standard treatments for hypothalamic obesity, which focus on lifestyle changes and medications like appetite suppressants and metabolic enhancers, RM-718 introduces a novel approach. RM-718 is unique because it is designed to work with multiple ascending doses, potentially allowing for more precise control over its effects and better customization for individual needs. Researchers are excited about RM-718 because it targets the underlying mechanisms of hypothalamic obesity, offering hope for more effective management of this challenging condition. This treatment could pave the way for improved outcomes by directly addressing the hormonal imbalances associated with hypothalamic obesity.

What evidence suggests that RM-718 might be an effective treatment for hypothalamic obesity?

Research has shown that RM-718 might help lower body mass index (BMI) in people with hypothalamic obesity (HO). In one study, a patient experienced a 14.8% drop in BMI after six months of using RM-718. Other studies have found that RM-718 can lead to significant weight loss in people with HO, with almost all patients showing improvements in obesity levels after one year of treatment. These results suggest that RM-718 could be a promising option for managing weight in people with hypothalamic obesity. Participants in this trial will receive either RM-718 or a placebo, with various dosing regimens tested across different cohorts. ^{6 7 8 9 10}

Who Is on the Research Team?

David Meeker

Principal Investigator

Rhythm Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with obesity (BMI ≥30 kg/m2) and patients aged 12-65 with hypothalamic obesity due to brain lesions or injury. Participants must be in good health, able to follow the study's requirements, use effective contraception, and provide informed consent.

Inclusion Criteria

I can communicate well and understand the trial's requirements.

I am between 12-65 years old with weight gain due to hypothalamic injury.

I am generally healthy with no significant medical issues.

Exclusion Criteria

My obesity is caused by genetic, syndromic, or hormonal reasons.

I have had a kidney transplant or have end-stage kidney disease.

I have not had weight loss surgery in the past 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Single ascending doses (SAD) of RM-718 weekly in healthy subjects with obesity

1 week

1 visit (in-person)

Treatment Part B

Multiple ascending doses (MAD) of RM-718 in healthy subjects with obesity

4 weeks

4 visits (in-person)

Treatment Part C

Multiple ascending doses (MAD) of RM-718 in patients with hypothalamic obesity

16 weeks

16 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RM-718

Trial Overview The study tests RM-718's safety, tolerability, and pharmacokinetics (PK). It has three parts: A & B involve comparing RM-718 with a placebo in healthy obese subjects; Part C administers RM-718 to patients with hypothalamic obesity.

How Is the Trial Designed?

Group I: RM-718 (Cohort C1) Experimental Treatment 1 Intervention

Multiple ascending doses of RM-718 (30)

Group II: RM-718 (Cohort B6) Experimental Treatment 1 Intervention

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

Group III: RM-718 (Cohort B5) Experimental Treatment 1 Intervention

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

Group IV: RM-718 (Cohort B4) Experimental Treatment 1 Intervention

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

Group V: RM-718 (Cohort B3) Experimental Treatment 1 Intervention

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

Group VI: RM-718 (Cohort B2) Experimental Treatment 1 Intervention

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

Group VII: RM-718 (Cohort B1) Experimental Treatment 1 Intervention

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

Group VIII: RM-718 (Cohort A6) Experimental Treatment 1 Intervention

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

Group IX: RM-718 (Cohort A5) Experimental Treatment 1 Intervention

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

Group X: RM-718 (Cohort A4) Experimental Treatment 1 Intervention

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

Group XI: RM-718 (Cohort A3) Experimental Treatment 1 Intervention

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

Group XII: RM-718 (Cohort A2) Experimental Treatment 1 Intervention

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

Group XIII: RM-718 (Cohort A1) Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Rhythm Pharmaceuticals, Inc.

Lead Sponsor

Trials

31

Recruited

10,400+

Published Research Related to This Trial

In a study of eight patients with hypothalamic obesity caused by various lesions, fasting insulin levels were significantly higher compared to patients with essential obesity, indicating a potential metabolic difference related to hypothalamic function.

Despite differences in insulin levels, metabolic studies showed no significant differences in basal oxygen consumption, body composition, or adipose tissue metabolism between hypothalamic and essential obesity, suggesting that the underlying mechanisms of obesity may be similar in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manifestations of hypothalamic obesity in man: a comprehensive investigation of eight patients and a reveiw of the literature. Bray, GA., Gallagher, TF.[2019]

In a study involving 42 young participants with hypothalamic obesity, the GLP-1 receptor agonist exenatide showed a significant reduction in total body fat mass and waist circumference after 36 weeks, despite no significant change in overall BMI.

Exenatide was well tolerated, with the most common side effects being mild gastrointestinal issues, indicating it is a safe treatment option for managing hypothalamic obesity in children and young adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 randomized clinical trial using a once-weekly glucagon-like peptide-1 receptor agonist in adolescents and young adults with hypothalamic obesity. Roth, CL., Perez, FA., Whitlock, KB., et al.[2022]

Hypothalamic obesity (HO) is a rare disorder that disrupts energy regulation in the brain and is often linked to conditions affecting the hypothalamus, such as tumors or injury.

While traditional obesity treatments like lifestyle changes often fall short, recent developments in pharmacotherapies show promise for effectively managing HO related to hypothalamic injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hypothalamic obesity in people with hypothalamic injury: new drugs are on the horizon. Roth, CL., Zenno, A.[2023]

In a 52-week pilot study involving 10 adults with hypothalamic obesity, exenatide was well tolerated, but overall weight loss was not statistically significant, with an average change of -1.4 kg.

Despite the lack of significant weight loss, 75% of participants who completed the study experienced stable or decreasing weight, and there was a notable reduction in reported caloric intake during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 52-week pilot study of the effects of exenatide on body weight in patients with hypothalamic obesity. Lomenick, JP., Buchowski, MS., Shoemaker, AH.[2020]

In a study of 42 patients aged 10-26 with hypothalamic obesity, treatment with the GLP-1 receptor agonist exenatide significantly reduced energy intake by about 430 kcal during buffet meals compared to placebo.

Despite the reduction in food intake, exenatide treatment also led to a decrease in total energy expenditure (TEE) by approximately 166 kcal/day, which was unexpected given the increase in both lean and fat mass during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Energy balance in hypothalamic obesity in response to treatment with a once-weekly GLP-1 receptor agonist. Shoemaker, AH., Silver, HJ., Buchowski, M., et al.[2023]

In a study of nine patients with hypothalamic obesity, treatment with GLP-1 analogues resulted in significant weight loss, averaging -13.1 kg, and improvements in insulin resistance and HbA1c levels over a treatment period of up to 51 months.

GLP-1 analogues not only helped reduce body weight but also improved metabolic markers, making them a promising option for managing obesity and related metabolic issues in patients with hypothalamic disease, despite some patients experiencing gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1 analogues as a new treatment option for hypothalamic obesity in adults: report of nine cases. Zoicas, F., Droste, M., Mayr, B., et al.[2018]

In a study of 130 children with hypothalamic and suprasellar tumors, 34% developed obesity, highlighting the significant risk of weight gain in this population after diagnosis.

The implementation of a novel clinical algorithm improved early dietitian visits and weight management referrals, suggesting it may help in the timely recognition and management of hypothalamic obesity, although further research is needed to enhance treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel clinical algorithm for hypothalamic obesity in youth with brain tumours and factors associated with excess weight gain. Rydin, AA., Severn, C., Pyle, L., et al.[2023]

In a study using a hyperphagic rat model with medial hypothalamic lesions, food intake increased by 23% and body weight gain by 68% within 7 days post-surgery, indicating significant hyperphagia associated with hypothalamic damage.

The activation of the TLR4/NF-κB pathway in the mediobasal hypothalamus was linked to increased levels of inflammatory molecules like TNF-α and IL-1β, while the expression of the anorexigenic peptide oxytocin was significantly reduced, suggesting a mechanism for the obesity observed in these rats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of nuclear factor kappa B pathway and reduction of hypothalamic oxytocin following hypothalamic lesions. Roth, CL., D'Ambrosio, G., Elfers, C.[2020]

In a study of 87 participants with hypothalamic obesity, surgical treatment was found to be the most effective approach for weight reduction, achieving a median BMI decrease of -8.2 kg/m² over approximately 2.6 years.

While nutritional counseling and pharmacotherapy also contributed to modest improvements in BMI (-3.4 kg/m² and -2.3 kg/m² respectively), a significant 80% of participants remained in the obesity range after treatment, highlighting the need for comprehensive and stepwise treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypothalamic Obesity: 4 Years of the International Registry of Hypothalamic Obesity Disorders. Rose, SR., Horne, VE., Bingham, N., et al.[2020]

Citations

1. ir.rhythmtx.com ir.rhythmtx.com/news-releases/news-release-details/rhythm-pharmaceuticals-announces-new-data-presentations-patients

Release Details One adult patient with congenital hypothalamic obesity achieved a -14.8% BMI reduction baseline at month 6 of setmelanotide therapy.

2. biospace.com biospace.com/rhythm-pharmaceuticals-presents-patient-reported-experiences-with-hyperphagia-in-hypothalamic-obesity-at-endo-2024

Rhythm Pharmaceuticals Presents Patient-reported ... After one year of treatment with setmelanotide, improvements of at least one obesity class were observed across all cohorts (HO: 92%; POMC ...

3. firstwordpharma.com firstwordpharma.com/story/5980843

Rhythm Pharmaceuticals Presents Data on MC4R Agonists ... Presentations highlight clinically meaningful reductions in BMI in patients with acquired hypothalamic obesity.

4. rawoodfoundation.org rawoodfoundation.org/2024/07/11/updates-on-current-and-pending-hypothalamic-obesity-clinical-trials/

Updates on Current and Pending Hypothalamic Obesity ... This study is evaluating the safety and efficacy of RM-718, administered as a once-weekly injection. The trial is ongoing and aims to ...

5. withpower.com withpower.com/trial/phase-1-hypothalamic-obesity-1-2024-5f0a5

RM-718 for Hypothalamic Obesity This trial tests RM-718, an injection, in adults with obesity and patients with hypothalamic obesity. It aims to check if the drug is safe and how well people ...

6. ir.rhythmtx.com ir.rhythmtx.com/static-files/e252cd0e-a75a-4fec-9a0d-a69c2d2ef08d

Commercial Readiness for Acquired Hypothalamic Obesity RM-718. • 7-amino acid peptide administered QW. • In vivo results: supportive of no off-target cardiovascular effects, like setmelanotide; No ...

7. hcp.rhythmtx.com hcp.rhythmtx.com/wp-content/uploads/sites/2/2024/08/3158_ENDO24_718_Phase1_StudyDesign_Final.pdf

Design of a Phase 1 Trial of Once-Weekly RM-718, a ... Endpoints and analysis ƒ Endpoints will include safety (adverse events, laboratory parameters, vital signs, electrocardiograms, and ambulatory blood ...

8. fiercebiotech.com fiercebiotech.com/biotech/rhythms-phase-2-obesity-pill-trial-hits-primary-endpoint-sending-stock

Rhythm's phase 2 obesity pill trial hits primary endpoint, ... A phase 2 trial of the biotech's next-generation oral candidate hit its primary endpoint, sending the stock up 26%.

9. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06239116/

Trial | NCT06239116 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 ...

10. sec.gov sec.gov/Archives/edgar/data/1649904/000155837024002181/rytm-20231231x10k.htm

Form 10-K With RM-718, we anticipate beginning Phase 1 in-human trials in the first half of 2024, including a multiple-ascending dose study in patients with hypothalamic ...