Hypothalamic ObesityPhase 2NCT06046443

A Study to Assess Efficacy and Safety of LB54640 in Patients With Hypothalamic Obesity

A Phase 2 study testing Bivamelagon in people with Hypothalamic Obesity, run by Rhythm Pharmaceuticals, Inc. at 10 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 12 years and older
Conditions the study is for: Hypothalamic Obesity
What is being tested?: Bivamelagon
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 28 participants
Where: 10 sitesin 2 countries
Study dates: 11 Jul 2024to 9 Feb 2026
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Documented evidence of acquired hypothalamic obesity (HO)
Age 12 years and older
Weight gain associated with the hypothalamic injury and a body mass index (BMI) of ≥30 kg/m^2 for participants ≥18 years of age or BMI ≥95th percentile for age and sex for participants <18 years of age
Male and female participants agreed to follow study contraception requirements and use a highly effective form of contraception throughout the study and for 90 days after the study

Who cannot join

Weight loss >2% in the previous 3 months for participants ≥18 years of age or >2% reduction in BMI for participants <18 years of age
History of major surgical procedure within 30 days
HbA1c >10.9%
Fasting glucose level >270 mg/dL
Previous use of MC4R agonists
Diagnosis of Prader-Willi syndrome (PWS) or Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor syndrome (ROHHADNET)

Show all 10Show fewer

Diagnosis of severe psychiatric disorders; any suicidal ideation, attempt or behavior
History or close family history of skin cancer or melanoma
Clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study and/or confound the results
Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

10 sites in 2 countries.

Country

City, postcode or hospital

10 sites in 2 countries

United States7 sites

Children's Hospital Colorado
Aurora, Colorado, 80045
Tufts Medical Center
Boston, Massachusetts, 02111
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514
University of Iowa Children's Hospital
Iowa City, Iowa, 52242
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Columbia University
New York, New York, 10027
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73112

Other trials in United States

United Kingdom3 sites

Birmingham Women's and Children's NHS Foundation Trust
Birmingham, B15 2TG
University of Cambridge
Cambridge, CB2 1TN
Great Ormond Street Hospital for Children
London, WC1N 3JH

Other trials in United Kingdom

About this study

Official title: A Randomized, Placebo-controlled, Double-Blind Phase 2 Study to Assess Efficacy and Safety of LB54640 in Patients With Hypothalamic Obesity, With an Open-Label Extension

The goal of this study was to determine how well LB54640 (also known as bivamelagon) worked and how safe it was in participants with Hypothalamic Obesity (HO). The study evaluated the effect of bivamelagon on safety, weight reduction, hunger, and quality of life in participants 12 years of age and older with HO. Participants took an oral daily dose of either bivamelagon (low, middle, or high dose) or placebo through Week 14. Eligible participants who consented to continue in the study after Week 14 took an oral daily dose of bivamelagon through Week 52.

Conditions: Hypothalamic Obesity
Being tested: Bivamelagon, Placebo
Keywords: melanocortin 4 receptor, MC4R, MC4R agonism
Medical subject headings: Sexual Infantilism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BivamelagonDrug
Also called LB54640
Oral daily administration
PlaceboDrug
Placebo matched to LB54640

Study groups in NCT06046443
Study group	Role	What they receive
Bivamelagon Low dose (200 milligrams [mg])	Experimental	Participants were randomized to receive bivamelagon low dose (200 mg), middle dose (400 mg), or high dose (600 mg), or placebo by oral administration in a 1:1:1:1 ratio. Receives: Drug: Bivamelagon
Bivamelagon Middle dose (400 mg)	Experimental	Participants were randomized to receive bivamelagon low dose (200 mg), middle dose (400 mg), or high dose (600 mg), or placebo by oral administration in a 1:1:1:1 ratio. Receives: Drug: Bivamelagon
Bivamelagon High dose (600 mg)	Experimental	Participants were randomized to receive bivamelagon low dose (200 mg), middle dose (400 mg), or high dose (600 mg), or placebo by oral administration in a 1:1:1:1 ratio. Receives: Drug: Bivamelagon
Placebo	Placebo comparator	Participants were randomized to receive bivamelagon low dose (200 mg), middle dose (400 mg), or high dose (600 mg), or placebo by oral administration in a 1:1:1:1 ratio. Receives: Drug: Placebo
Open-label Bivamelagon	Experimental	Eligible participants who provided consent to continue into the open-label portion of the study received open-label bivamelagon. Receives: Drug: Bivamelagon

What is being measured

The primary outcome is the main question the study is designed to answer.

Treatment Phase: Mean Percentage Change From Baseline to Week 14 in Body Mass Index (BMI)
BMI was calculated as weight (kilograms [kg])/height (squared meters [m^2]). Least square mean (LSM) and standard error (SE) were calculated using analysis of covariance (ANCOVA) model with treatment group, randomization stratification factor (≥18 years old vs <18 years old) as factors and baseline BMI as a covariate.
Measured: Baseline, Week 14

Secondary outcomes (34)

Treatment Phase: Mean Percentage Change From Baseline to Weeks 6 and 10 in BMI
BMI was calculated as weight (kg)/height (m^2). Percentage change from baseline was calculated as: (post-baseline result - baseline result) / baseline result*100%.
Measured: Baseline, Week 6 and Week 10
Treatment Phase: Mean Change From Baseline in BMI
BMI was calculated as weight (kg)/height (m^2).
Measured: Baseline, Week 6, Week 10, and Week 14
Treatment Phase (Participants < 18 Years): Mean Change From Baseline in the Gender- and Age-specific BMI Z-Score
The BMI Z-scores were measures of relative weight adjusted for child age and sex. Given a child's age, sex, BMI, and an appropriate reference standard, a BMI Z-score can be determined. The BMI Z-scores were calculated using the Lambda Mu and Sigma method following the 2007 World Health Organization (WHO) reference. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease in BMI Z-score (< 0) indicates a reduction in BMI from Baseline whereas an increase in BMI-Z score (> 0) indicated an increase in BMI from Baseline.
Measured: Baseline, Week 6, Week 10, and Week 14
Treatment Phase (Participants < 18 Years): Mean Change From Baseline in the Percentage of the Gender- and Age-specific 95th Percentile of BMI
The BMI values were expressed as a percentage of the gender- and age-specific 95th percentile following the 2000 Centers for Disease Control (CDC) BMI-for-Age Growth Charts form.
Measured: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Mean Change From Baseline in Body Weight
Measured: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Mean Percentage Change From Baseline in Body Weight
Percentage change from baseline was calculated as: (post-baseline result - baseline result) / baseline result*100%.
Measured: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Percentage of Participants Who Achieved at Least a ≥5% or ≥10% Reduction in Body Weight
Measured: Baseline to Week 14
Treatment Phase: Percentage of Participants Who Achieved at Least a ≥5% or ≥10% Reduction in BMI
BMI was calculated as weight (kg)/height (m^2).
Measured: Baseline to Week 14
Treatment Phase: Mean Change From Baseline in Waist Circumference
The waist circumference was defined as the minimal abdominal circumference located midway between the lower rib margin and the iliac crest.
Measured: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Mean Percentage Change From Baseline in Waist Circumference
The waist circumference was defined as the minimal abdominal circumference located midway between the lower rib margin and the iliac crest. Percentage change from baseline was calculated as: (post-baseline result - baseline result) / baseline result*100%.
Measured: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Mean Change From Baseline in Waist-to-hip Circumference Ratio
The waist circumference was defined as the minimal abdominal circumference located midway between the lower rib margin and the iliac crest. The hip circumference was defined as the widest circumference around the buttocks. The waist-to-hip ratio was calculated as waist circumference divided by hip circumference.
Measured: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Mean Percentage Change From Baseline in Waist-to-hip Circumference Ratio
The waist circumference was defined as the minimal abdominal circumference located midway between the lower rib margin and the iliac crest. The hip circumference was defined as the widest circumference around the buttocks. The waist-to-hip ratio was calculated as waist circumference divided by hip circumference. Percentage change from baseline was calculated as: (post-baseline result - baseline result) / baseline result*100%.
Measured: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Mean Change From Baseline in Body Composition
Body composition included fat and lean body mass and was assessed by dual energy x-ray absorptiometry (DEXA).
Measured: Baseline, Week 14
Treatment Phase: Mean Percentage Change From Baseline in Body Composition
Body composition included fat and lean body mass and was assessed by DEXA. Percentage change from baseline was calculated as: (post-baseline result - baseline result) / baseline result*100%.
Measured: Baseline, Week 14
Treatment Phase: Mean Change From Baseline in the Weekly Average of the Daily Most Hunger Score
Participants who were able to validly and reliably self-report were administered "Hunger Questions for Participants ≥12 Years of Age©." This questionnaire comprised 2 items (average and most hunger) that were designed to be evaluated separately (rather than as a composite score). Each item asked participants to rate their hunger on an 11-point numeric rating scale ranging from 0 to 10 (0 = not hungry at all and 10 = hungriest possible) with a recall period of 24 hours. Data reported are for mean change from baseline in the weekly average daily most hunger score.
Measured: Baseline, Week 14
Treatment Phase: Mean Change From Baseline in the Weekly Average of the Symptoms of Hyperphagia Composite Score
Participants who were able to self-report were administered the Symptoms of Hyperphagia: Patient© Version. The questionnaire consisted of 4 items related to the frequency of a participant's hyperphagia symptoms on a scale (never [score 0], 1 or 2 times [score 1], 3 or more times [score 2]) over the previous 24 hours. Caregivers of participants who could not self report were administered the Symptoms of Hyperphagia: Caregiver© Version which consisted of 5 items that included caregivers assessing the frequency of hyperphagia symptoms on a scale (never [score 0], 1 or 2 times [score 1], 3 or more times [score 2]) over the previous 24 hours for the person in their care. The composite score was derived by adding up all item scores and dividing by total number of items answered. The full range of the composite score was 0-2, with higher scores representing more hyperphagia. Data are reported for mean change from baseline in weekly average of symptoms of hyperphagia composite score.
Measured: Baseline, Week 14
Open-label Extension Phase: Mean Change From Baseline in BMI
BMI was calculated as weight (kg)/height (m^2).
Measured: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Percentage Change From Baseline in BMI
BMI was calculated as weight (kg)/height (m^2). Percentage change from baseline was calculated as: (post-baseline result - baseline result) / baseline result*100%.
Measured: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Change From Baseline in Body Weight
Measured: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Percentage Change From Baseline in Body Weight
Percentage change from baseline was calculated as: (post-baseline result - baseline result) / baseline result*100%.
Measured: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Change From Baseline in Waist Circumference
The waist circumference was defined as the minimal abdominal circumference located midway between the lower rib margin and the iliac crest.
Measured: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Percentage Change From Baseline in Waist Circumference
The waist circumference was defined as the minimal abdominal circumference located midway between the lower rib margin and the iliac crest. Percentage change from baseline was calculated as: (post-baseline result - baseline result) / baseline result*100%.
Measured: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Change From Baseline in Waist-to-hip Circumference Ratio
The waist circumference was defined as the minimal abdominal circumference located midway between the lower rib margin and the iliac crest. The hip circumference was defined as the widest circumference around the buttocks. The waist-to-hip ratio was calculated as waist circumference divided by hip circumference.
Measured: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Percentage Change From Baseline in Waist-to-hip Circumference Ratio
The waist circumference was defined as the minimal abdominal circumference located midway between the lower rib margin and the iliac crest. The hip circumference was defined as the widest circumference around the buttocks. The waist-to-hip ratio was calculated as waist circumference divided by hip circumference. Percentage change from baseline was calculated as: (post-baseline result - baseline result) / baseline result*100%.
Measured: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Change From Baseline in Body Composition
Body composition included fat and lean body mass and was assessed by DEXA.
Measured: Baseline, Week 52
Open-label Extension Phase: Mean Percentage Change From Baseline in Body Composition
Body composition included fat and lean body mass and was assessed by DEXA. Percentage change from baseline was calculated as: (post-baseline result - baseline result) / baseline result*100%.
Measured: Baseline, Week 52
Treatment Phase: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) or Adverse Event of Special Interest (AESI)
A TEAE was any undesirable and unintended medical event occurring to a participant in a clinical study and which did not necessarily have a causal relationship with the study drug, with onset or worsening after the start of study drug. AESIs were events of scientific and medical interest specific to further the understanding of the safety profile of the study drug. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Measured: Day 1 to Week 14
Open-label Extension Phase: Number of Participants Who Experienced a TEAE or AESI
A TEAE was any undesirable and unintended medical event occurring to a participant in a clinical study and which does not necessarily have a causal relationship with the study drug, with onset or worsening after the start of study drug. AESIs were events of scientific and medical interest specific to the further understanding of the safety profile of the study drug. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Measured: Week 14 to Week 56
Treatment Phase: Number of Participants Who Experienced a Mild, Moderate, Severe, Life-threatening or Fatal TEAE
TEAEs were evaluated by the investigator according to the definitions below using the following guidelines:
- Mild - Asymptomatic or mild symptoms; clinical or diagnostic observations only; no intervention indicated; no disruption to daily activity.
- Moderate - Discomfort sufficient to reduce or affect normal daily activity.
- Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; inability to work or perform normal daily activity.
- Life-threatening consequences; urgent intervention indicated.
- Fatal outcome.
A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Measured: Day 1 to Week 14
Open-label Extension Phase: Number of Participants Who Experienced a Mild, Moderate, Severe, Life-threatening or Fatal TEAE
TEAEs were evaluated by the investigator according to the definitions below using the following guidelines:
- Mild - Asymptomatic or mild symptoms; clinical or diagnostic observations only; no intervention indicated; no disruption to daily activity.
- Moderate - Discomfort sufficient to reduce or affect normal daily activity.
- Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; inability to work or perform normal daily activity.
- Life-threatening consequences; urgent intervention indicated.
- Fatal outcome.
A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Measured: Week 14 to Week 56
Treatment Phase: Maximum Observed Concentration of Bivamelagon in Plasma (Cmax)
Pharmacokinetic (PK) parameters were derived using noncompartmental methods. Cmax was obtained directly from the observed concentration versus time data. At Week 0, all participants received bivamelagon 200 mg QD. At Week 10, participants received their maximum assigned bivamelagon dose QD.
Measured: Week 0 and Week 10: Pre-dose and 1, 2, 4, 6, and 24 hours post-dose
Treatment Phase: Time to Cmax (Tmax)
PK parameters were derived using noncompartmental methods. At Week 0, all participants received bivamelagon 200 mg QD. At Week 10, participants received their maximum assigned bivamelagon dose QD.
Measured: Week 0 and Week 10: Pre-dose and 1, 2, 4, 6, and 24 hours post-dose
Treatment Phase: Area Under the Concentration-time Curve From 0 to Last Quantifiable Concentration (AUC0-t)
PK parameters were derived using noncompartmental methods.AUC0-t was calculated by the linear up/log down trapezoidal summation. At Week 0, all participants received bivamelagon 200 mg QD. At Week 10, participants received their maximum assigned bivamelagon dose QD.
Measured: Week 0 and Week 10: Pre-dose and 1, 2, 4, 6, and 24 hours post-dose
Treatment Phase: Trough Plasma Concentration (Ctrough)
PK parameters were derived using noncompartmental methods. At Week 0, all participants received bivamelagon 200 mg QD. At Week 10, participants received their maximum assigned bivamelagon dose QD.
Measured: Weeks 1, 2, 6, 10, and 14: Pre-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Jul 20249 Feb 2026

First posted21 Sep 2023
Study start11 Jul 2024
Primary completion9 Feb 2026
Study completion9 Feb 2026

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hypothalamic ObesityStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06046443
Sponsor's protocol ID: LG-MCCL005
Status last verified: Oct 2026
First submitted: 14 Sep 2023
Last updated: 30 Oct 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hypothalamic Obesity trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Placebo-controlled, Double-Blind Phase 2 Study to Assess Efficacy and Safety of LB54640 in Patients With Hypothalamic Obesity, With an Open-Label Extension
ClinicalTrials.gov ID: NCT06046443
Acronym / sponsor ID: LG-MCCL005
Conditions: Hypothalamic Obesity
Keywords: melanocortin 4 receptor, MC4R, MC4R agonism
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: Rhythm Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 11 Jul 2024 (actual)
Primary completion: 9 Feb 2026 (actual)
Study completion: 9 Feb 2026 (actual)
First posted: 21 Sep 2023 (actual)
Results: Posted 30 Oct 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 5

Arm	Type	Receives
Bivamelagon Low dose (200 milligrams [mg])	Experimental	Drug: BivamelagonParticipants were randomized to receive bivamelagon low dose (200 mg), middle dose (400 mg), or high dose (600 mg), or placebo by oral administration in a 1:1:1:1 ratio.
Bivamelagon Middle dose (400 mg)	Experimental	Drug: BivamelagonParticipants were randomized to receive bivamelagon low dose (200 mg), middle dose (400 mg), or high dose (600 mg), or placebo by oral administration in a 1:1:1:1 ratio.
Bivamelagon High dose (600 mg)	Experimental	Drug: BivamelagonParticipants were randomized to receive bivamelagon low dose (200 mg), middle dose (400 mg), or high dose (600 mg), or placebo by oral administration in a 1:1:1:1 ratio.
Placebo	Placebo comparator	Drug: PlaceboParticipants were randomized to receive bivamelagon low dose (200 mg), middle dose (400 mg), or high dose (600 mg), or placebo by oral administration in a 1:1:1:1 ratio.
Open-label Bivamelagon	Experimental	Drug: BivamelagonEligible participants who provided consent to continue into the open-label portion of the study received open-label bivamelagon.

Who may qualify

Ages: 12 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (4 listed)

Documented evidence of acquired hypothalamic obesity (HO)
Age 12 years and older
Weight gain associated with the hypothalamic injury and a body mass index (BMI) of ≥30 kg/m^2 for participants ≥18 years of age or BMI ≥95th percentile for age and sex for participants <18 years of age
Male and female participants agreed to follow study contraception requirements and use a highly effective form of contraception throughout the study and for 90 days after the study

Key exclusion criteria (10 listed)

Weight loss >2% in the previous 3 months for participants ≥18 years of age or >2% reduction in BMI for participants <18 years of age
History of major surgical procedure within 30 days
HbA1c >10.9%
Fasting glucose level >270 mg/dL
Previous use of MC4R agonists

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BivamelagonAlso: LB54640Oral daily administration	Drug	Bivamelagon High dose (600 mg), Bivamelagon Low dose (200 milligrams [mg]), Bivamelagon Middle dose (400 mg), Open-label Bivamelagon
PlaceboPlacebo matched to LB54640	Drug	Placebo

Primary outcome

Treatment Phase: Mean Percentage Change From Baseline to Week 14 in Body Mass Index (BMI)
Time frame: Baseline, Week 14
BMI was calculated as weight (kilograms [kg])/height (squared meters [m^2]). Least square mean (LSM) and standard error (SE) were calculated using analysis of covariance (ANCOVA) model with treatment group, randomization stratification factor (≥18 years old vs <18 years old) as factors and baseline BMI as a covariate.

34 secondary outcomes

Treatment Phase: Mean Percentage Change From Baseline to Weeks 6 and 10 in BMI
Time frame: Baseline, Week 6 and Week 10
Treatment Phase: Mean Change From Baseline in BMI
Time frame: Baseline, Week 6, Week 10, and Week 14
Treatment Phase (Participants < 18 Years): Mean Change From Baseline in the Gender- and Age-specific BMI Z-Score
Time frame: Baseline, Week 6, Week 10, and Week 14
Treatment Phase (Participants < 18 Years): Mean Change From Baseline in the Percentage of the Gender- and Age-specific 95th Percentile of BMI
Time frame: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Mean Change From Baseline in Body Weight
Time frame: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Mean Percentage Change From Baseline in Body Weight
Time frame: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Percentage of Participants Who Achieved at Least a ≥5% or ≥10% Reduction in Body Weight
Time frame: Baseline to Week 14
Treatment Phase: Percentage of Participants Who Achieved at Least a ≥5% or ≥10% Reduction in BMI
Time frame: Baseline to Week 14
Treatment Phase: Mean Change From Baseline in Waist Circumference
Time frame: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Mean Percentage Change From Baseline in Waist Circumference
Time frame: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Mean Change From Baseline in Waist-to-hip Circumference Ratio
Time frame: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Mean Percentage Change From Baseline in Waist-to-hip Circumference Ratio
Time frame: Baseline, Week 6, Week 10, and Week 14
Treatment Phase: Mean Change From Baseline in Body Composition
Time frame: Baseline, Week 14
Treatment Phase: Mean Percentage Change From Baseline in Body Composition
Time frame: Baseline, Week 14
Treatment Phase: Mean Change From Baseline in the Weekly Average of the Daily Most Hunger Score
Time frame: Baseline, Week 14
Treatment Phase: Mean Change From Baseline in the Weekly Average of the Symptoms of Hyperphagia Composite Score
Time frame: Baseline, Week 14
Open-label Extension Phase: Mean Change From Baseline in BMI
Time frame: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Percentage Change From Baseline in BMI
Time frame: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Change From Baseline in Body Weight
Time frame: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Percentage Change From Baseline in Body Weight
Time frame: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Change From Baseline in Waist Circumference
Time frame: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Percentage Change From Baseline in Waist Circumference
Time frame: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Change From Baseline in Waist-to-hip Circumference Ratio
Time frame: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Percentage Change From Baseline in Waist-to-hip Circumference Ratio
Time frame: Baseline, Week 28 and Week 52
Open-label Extension Phase: Mean Change From Baseline in Body Composition
Time frame: Baseline, Week 52
Open-label Extension Phase: Mean Percentage Change From Baseline in Body Composition
Time frame: Baseline, Week 52
Treatment Phase: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) or Adverse Event of Special Interest (AESI)
Time frame: Day 1 to Week 14
Open-label Extension Phase: Number of Participants Who Experienced a TEAE or AESI
Time frame: Week 14 to Week 56
Treatment Phase: Number of Participants Who Experienced a Mild, Moderate, Severe, Life-threatening or Fatal TEAE
Time frame: Day 1 to Week 14
Open-label Extension Phase: Number of Participants Who Experienced a Mild, Moderate, Severe, Life-threatening or Fatal TEAE
Time frame: Week 14 to Week 56
Treatment Phase: Maximum Observed Concentration of Bivamelagon in Plasma (Cmax)
Time frame: Week 0 and Week 10: Pre-dose and 1, 2, 4, 6, and 24 hours post-dose
Treatment Phase: Time to Cmax (Tmax)
Time frame: Week 0 and Week 10: Pre-dose and 1, 2, 4, 6, and 24 hours post-dose
Treatment Phase: Area Under the Concentration-time Curve From 0 to Last Quantifiable Concentration (AUC0-t)
Time frame: Week 0 and Week 10: Pre-dose and 1, 2, 4, 6, and 24 hours post-dose
Treatment Phase: Trough Plasma Concentration (Ctrough)
Time frame: Weeks 1, 2, 6, 10, and 14: Pre-dose

Results and safety

Results posted to the registry on 30 Oct 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Bivamelagon 200 mg	6	6
Bivamelagon 400 mg	7	6
Bivamelagon 600 mg	8	8
Placebo	7	7

Primary outcome: Treatment Phase: Mean Percentage Change From Baseline to Week 14 in Body Mass Index (BMI)

Time frame: Baseline, Week 14. Least squares mean (Standard Error). Unit: percentage change

Measure	Treatment Phase: Bivamelagon 200 mg n = 6	Treatment Phase: Bivamelagon 400 mg n = 7	Treatment Phase: Bivamelagon 600 mg n = 8	Treatment Phase: Placebo n = 7
Value	-2.62 (1.683)	-8.39 (1.738)	-9.98 (1.557)	2.52 (1.868)

Treatment Phase: Bivamelagon 200 mg vs Treatment Phase: Placebo: Least Square Mean Difference: -5.24 (90% CI -9.02 to -1.46), p = 0.0227, ANCOVA
Treatment Phase: Bivamelagon 400 mg vs Treatment Phase: Placebo: Least Square Mean Difference: -11.00 (90% CI -14.80 to -7.21), p = 0.0000, ANCOVA
Treatment Phase: Bivamelagon 600 mg vs Treatment Phase: Placebo: Least Square Mean Difference: -12.59 (90% CI -16.32 to -8.87), p = 0.0000, ANCOVA

Population analysed: The mITT set included all randomized participants in the Treatment Phase who were exposed to at least one dose of study drug.

34 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment Phase: Day 1 to Week 14. Open-label Extension Phase: Week 14 to Week 56. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment Phase: Bivamelagon 200 mg	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Treatment Phase: Bivamelagon 400 mg	1 of 7 (14.3%)	7 of 7 (100%)	0 of 7
Treatment Phase: Bivamelagon 600 mg	0 of 8 (0%)	8 of 8 (100%)	0 of 8
Treatment Phase: Placebo	1 of 7 (14.3%)	6 of 7 (85.7%)	0 of 7
Open-label Extension Phase: Bivamelagon 200 mg to 600 mg	2 of 6 (33.3%)	6 of 6 (100%)	0 of 6
Open-label Extension Phase: Bivamelagon 400 mg to 600 mg	1 of 6 (16.7%)	5 of 6 (83.3%)	0 of 6
Open-label Extension Phase: Bivamelagon 600 mg to 600 mg	1 of 7 (14.3%)	7 of 7 (100%)	0 of 7
Open-label Extension Phase: Placebo to Bivamelagon 600 mg	0 of 7 (0%)	7 of 7 (100%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David Meeker, MD study chair

Rhythm Pharmaceuticals, Inc.

10 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bivamelagon in people with Hypothalamic Obesity, run by Rhythm Pharmaceuticals, Inc. at 10 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment Phase: Mean Percentage Change From Baseline to Week 14 in Body Mass Index (BMI) (time frame: Baseline, Week 14). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06046443.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.