LY3971297 for Obesity

Recruiting at 6 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Must be taking: Antihypertensives, ACE inhibitors

Must not be taking: Phosphodiesterase inhibitors, Beta blockers

Disqualifiers: Cardiovascular, Renal, Psychiatric, others

Compensation: Varies

Number of Visits: Unknown

Duration: 60-90 days

225 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, LY3971297 (a long-acting atrial natriuretic peptide), to understand its side effects and behavior in the body. It focuses on both healthy individuals and those who are obese with high blood pressure. Participants will receive injections of either the treatment or a placebo (a substance with no active drug), and researchers will monitor the results. This trial might suit someone who is generally healthy or has obesity with stable high blood pressure and related conditions. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, for Part D, participants must have a stable dose of antihypertensive medications, and for Part G, participants can continue stable treatments for hypertension, type 2 diabetes, dyslipidemia, and hypothyroidism. Some medications like phosphodiesterase 5 inhibitors, long-acting nitrates, nitric oxide donors, and beta blockers are not allowed for Parts D and G.

Is there any evidence suggesting that LY3971297 is likely to be safe for humans?

Research has shown that LY3971297 is under study to determine its safety for humans. This treatment is tested through injections under the skin and directly into the bloodstream. LY3971297, a long-acting atrial natriuretic peptide, is being evaluated for its potential effects on conditions like obesity and high blood pressure.

In studies so far, researchers have administered LY3971297 in varying doses to both healthy individuals and those with obesity. The primary goal is to observe the body's response to the drug and identify any side effects. Since the study is in its early stages, specific information on side effects remains limited. This phase primarily focuses on assessing the drug's safety before progressing to larger studies.

Although data is currently limited, this phase is crucial for understanding any immediate reactions to the drug. Researchers closely monitor participants to ensure safety, allowing for the quick identification and management of potential side effects. As research progresses, more detailed safety information will become available. ^{1 2 3 4 5}

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

Researchers are excited about LY3971297 for obesity because it offers a fresh approach compared to existing treatments. Unlike current options that often focus on appetite suppression or calorie absorption, LY3971297 potentially targets metabolic processes directly. This treatment is unique because it is administered in multiple ways, including subcutaneous and intravenous methods, which might allow for more flexible dosing options. Additionally, the focus on healthy participants in diverse populations could help tailor the treatment to different genetic backgrounds, potentially increasing its effectiveness and safety profile across various groups.

What evidence suggests that LY3971297 might be an effective treatment for obesity?

Research shows that LY3971297 might aid in weight loss by boosting a natural hormone that helps break down fat. Studies have found a link between low levels of this hormone and weight gain. This drug is being developed to treat obesity, heart failure, and high blood pressure. Although human studies provide limited information, its mechanism suggests it could reduce weight by enhancing this hormone's activity. Participants in this trial will receive LY3971297 in various dosing regimens, including single and multiple ascending doses, to evaluate its effects. ^{1 2 3 5 6}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for healthy individuals or those with obesity and high blood pressure. Healthy participants should have a BMI of 18.5 to 35 kg/m2, while obese participants need a BMI of 30 to 40 kg/m2 and meet specific waist measurements. Certain parts require Chinese or Japanese descent. Participants must not have significant health issues, psychiatric disorders, risky blood pressures, recent large blood donations, heavy nicotine or alcohol use, nor take certain medications.

Inclusion Criteria

I am a man who agrees to follow contraception rules or a woman who cannot become pregnant.

I have obesity and high blood pressure, and my medication dose has been stable for the last 3 months.

I am obese with a BMI between 30-40 and my waist is at least 102 cm (men) or 89 cm (women).

Exclusion Criteria

I am using or plan to use long-acting nitrates or nitric oxide donors.

I am using or plan to use medications like Viagra or Cialis.

I have been diagnosed with a significant drop in blood pressure upon standing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single or multiple ascending doses of LY3971297 or placebo administered subcutaneously or intravenously

60-90 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment emergent adverse events and pharmacokinetics

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY3971297

Trial Overview The study tests LY3971297 injections in different groups: healthy people and those with obesity plus high BP. It checks the drug's safety profile by observing side effects and measures how it's absorbed and cleared from the body over approximately two to three months.

How Is the Trial Designed?

Group I: LY3971297 (Part G) Experimental Treatment 1 Intervention

Multiple doses of LY3971297 administered SC

Group II: LY3971297 (Part F) Experimental Treatment 1 Intervention

Single doses of LY3971297 administered intravenously (IV) in healthy participants

Group III: LY3971297 (Part E) Experimental Treatment 1 Intervention

Multiple doses of LY3971297 administered SC in healthy Japanese participants

Group IV: LY3971297 (Part D) Experimental Treatment 1 Intervention

Multiple ascending doses of LY3971297 administered SC

Group V: LY3971297 (Part C) Experimental Treatment 1 Intervention

Multiple ascending doses of LY3971297 administered SC in healthy Chinese participants

Group VI: LY3971297 (Part B) Experimental Treatment 1 Intervention

Multiple ascending doses of LY3971297 administered SC in healthy participants

Group VII: LY3971297 (Part A) Experimental Treatment 1 Intervention

Single ascending doses of LY3971297 administered subcutaneously (SC) in healthy participants

Group VIII: Placebo (Part A, B, C, D, E, & G) Placebo Group 1 Intervention

Placebo administered SC

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

A 6-month hypocaloric diet led to an average weight loss of 9.1 kg in overweight or obese patients, which improved various health markers like insulin resistance and blood pressure, but did not significantly change resting levels of atrial natriuretic peptide (ANP).

Exercise increased ANP release in these patients, suggesting that while weight loss affects how ANP is cleared from the body, regular physical activity is crucial for enhancing ANP levels, indicating that combining diet and exercise may be the best approach to address natriuretic peptide deficiencies associated with obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential response of the natriuretic peptide system to weight loss and exercise in overweight or obese patients. Haufe, S., Kaminski, J., Utz, W., et al.[2018]

In a study involving 77 participants (26 obese hypertensives, 26 obese normotensives, and 25 lean hypertensives), levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were found to be useful markers for identifying preclinical cardiac disease in obese individuals, particularly in relation to left ventricular (LV) diastolic dysfunction and hypertrophy.

ANP levels were higher in patients with LV diastolic dysfunction, while BNP levels were elevated in those with both LV hypertrophy and diastolic dysfunction, indicating that these peptides can help assess cardiac health in obese patients regardless of their blood pressure status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natriuretic peptides as markers of preclinical cardiac disease in obesity. Grandi, AM., Laurita, E., Selva, E., et al.[2015]

In a study of 2203 participants aged 30 and older, higher levels of plasma proANP1-98 were significantly associated with an increased risk of central obesity, with odds ratios indicating a clear dose-response relationship.

The findings suggest that elevated plasma proANP1-98 may serve as a marker or risk factor for central obesity, challenging the previously understood link between lower ANP levels and obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma proANP1-98 levels are positively associated with central obesity: A cross-sectional study in a general population of China. Zhu, Z., Zhang, Q., Peng, H., et al.[2018]

In a study of 693 healthy Scandinavian subjects, plasma pro-atrial-derived natriuretic peptide (proANP) concentrations were found to be unaffected by body mass index (BMI) and plasma glucose levels in fasting individuals, suggesting that proANP may not be a reliable biomarker for obesity or type 2 diabetes in this population.

The research introduced an optimized assay for measuring low concentrations of proANP, which could be useful for future studies investigating its role in conditions like obesity and diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose. Mark, PD., Hunter, I., Terzic, D., et al.[2017]

In a study of 100 patients undergoing left heart catheterization, obese individuals (BMI ≥ 30 kg/m²) were found to have significantly lower levels of B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) compared to nonobese individuals (BMI < 30 kg/m²).

The findings suggest that lower circulating levels of these natriuretic peptides in obese patients may play a role in the development of heart failure, highlighting a potential mechanism linking obesity to heart health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obese patients have lower B-type and atrial natriuretic peptide levels compared with nonobese. Khush, KK., Gerber, IL., McKeown, B., et al.[2019]

In a study of 2038 patients presenting with acute dyspnoea, adjusting the NT-proBNP cut-off levels for obesity improved the sensitivity for diagnosing acute heart failure (AHF) from 96.7% to 98.2%, allowing for better identification of patients at risk.

Lowering NT-proBNP cut-offs based on body mass index (BMI) also reduced the number of patients remaining in the 'gray zone' for diagnosis, enhancing the clinical utility of NT-proBNP in obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effect of obesity on N-terminal pro-B-type natriuretic peptide cut-off concentrations for the diagnosis of acute heart failure. Kozhuharov, N., Martin, J., Wussler, D., et al.[2023]

In an experimental study with obese rats, a 15-week caloric restriction led to a 40% reduction in body weight, which significantly increased circulating levels of atrial natriuretic peptide (ANP) and reduced adipocyte size.

Despite weight loss normalizing body fat, the rats still showed signs of cardiac hypertrophy, indicating that obesity can have lasting effects on heart structure, but the increased ANP may help promote diuresis and sodium balance during weight reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of experimental obesity and subsequent weight reduction upon circulating atrial natriuretic peptide. Crandall, DL., Ferraro, GD., Cervoni, P.[2020]

Citations

1. withpower.com withpower.com/trial/phase-1-hypertension-11-2023-3d6f9

LY3971297 for Obesity · Recruiting Participants for Phase ... LY3971297, a long-acting atrial natriuretic peptide, is unique because it may help with weight loss by increasing the levels of a natural hormone that promotes ...

2. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/ly-3971297-eli-lilly-and-co-obesity-likelihood-of-approval/

LY-3971297 by Eli Lilly and Co for Obesity: Likelihood of ... LY-3971297 is under development for the treatment of heart failure, obesity and hypertension. The drug candidate is administered through ...

3. trials.lilly.com trials.lilly.com/en-US/trial/438415

A Study of LY3971297 in Healthy Participants and ... - Lilly Trials The purpose of this study is to measure side effects of LY3971297 injection administered under the skin in healthy participants and obese participants with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3635959/

Inverse association of long-acting natriuretic peptide with ... It can be speculated that low levels of natriuretic peptide may lead to reduced lipolysis and excessive weight gain in obese patients, which may ...

5. synapse.patsnap.com synapse.patsnap.com/drug/9cbd280765d24c41ace412fe59ef7847

LY-3971297 - Drug Targets, Indications, Patents A single-ascending and multiple-ascending dose study of LY3971297 in healthy participants and participants with obesity and hypertension.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9219923/

Natriuretic Peptide-Based Novel Therapeutics This review summarizes attempts to develop novel natriuretic peptide-based therapeutics, including novel designer natriuretic peptides and oral drugs.