A Study of Tirzepatide (LY3298176) on the Reduction on Morbidity and Mortality in Adults With Obesity (SURMOUNT-MMO)

• ClinicalTrials.gov Identifier: NCT05556512
• Recruitment Status: Active, not recruiting
• First Posted: September 27, 2022
• Last Update Posted: April 19, 2024
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: September 22, 2022
• First Posted Date: September 27, 2022
• Last Update Posted Date: April 19, 2024
• Actual Study Start Date: October 11, 2022
• Estimated Primary Completion Date: October 7, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 22, 2022)

Time to First Occurrence of Any Component Event of Composite (All-Cause Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, Coronary Revascularization, or Heart Failure Events) [ Time Frame: Up to 5 Years ]

Time to first occurrence of any component event of composite, all-cause death, nonfatal MI, nonfatal stroke, coronary revascularization, or heart failure events that results in hospitalization or urgent visits.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 22, 2022)

• Time to Onset of Type 2 Diabetes (T2D) [ Time Frame: Up to 5 Years ]
• Hierarchical Composite of Renal Death or End-Stage Renal Disease (ESRD), Sustained Decline in Estimated Glomerular Filtration Rate (eGFR), and eGFR Slope [ Time Frame: Estimated from Baseline (Week 0) to Study Completion Up to 5 Years ]
  Hierarchical composite of time to first occurrence of renal death or ESRD, ≥57% sustained decline in eGFR, ≥40% sustained decline in eGFR, and eGFR slope difference >0.5 milliliter/minute/1.73 square meter/year (mL/min/1.73 m²/year) will be assessed by the win ratio. The reported unit will be the total "wins" for each treatment group from performing a hierarchical comparison of components.
• Time to First Occurrence of Any Component Event of Major Adverse Cardiovascular Events-3 (MACE-3) (CV Death, Nonfatal MI or Nonfatal Stroke) [ Time Frame: Up to 5 Years ]
  Time to first occurrence of any component event of MACE-3 (CV death, nonfatal MI or nonfatal stroke)
• Mean Change from Baseline Short Form-36 Version 2 (SF-36 v2) Acute Form Physical Functioning Domain Score [ Time Frame: Baseline, 2 Years ]
  The SF-36 v2 acute, 1-week recall version is a 36-item generic, participant-administered measure designed to assess the following 8 domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role - Emotional, and Mental Health. Each domain is scored individually and further aggregated into 2 health component summary scores, physical component and mental component summary. Scoring of each domain and both summary scores are norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function and/or better health.
• Time to the Occurrence of All-cause Death [ Time Frame: Up to 5 Years ]
• Time to First Occurrence of CV Death [ Time Frame: Up to 5 Years ]
• Time to First Occurrence of MI [ Time Frame: Up to 5 Years ]
• Time to First Occurrence of Stroke [ Time Frame: Up to 5 Years ]
• Time to First Occurrence of Coronary Revascularization [ Time Frame: Up to 5 Years ]
• Time to First Occurrence Heart Failure (HF) Events [ Time Frame: Up to 5 Years ]
  Time to first occurrence heart failure (HF) events that result in hospitalization or urgent visits
• Time to First Occurrence of Hospitalization for Unstable Angina [ Time Frame: Up to 5 Years ]
• Time to first occurrence of Hospitalization or Urgent Visit [ Time Frame: Up to 5 Years ]
  Time to first occurrence of hospitalization or urgent visit due to atrial fibrillation, or cardioversion or ablation for atrial fibrillation
• Time to First Occurrence of Any Component Event of the Composite Endpoint (eGFR, ESRD, or Renal Death) [ Time Frame: Up to 5 Years ]
  Time to first occurrence of any component event of the composite endpoint ≥40% sustained decline in eGFR, ESRD, or renal death.
• eGFR Slope [ Time Frame: Up to 5 Years ]
• Percent Change from Baseline in Body Weight [ Time Frame: Baseline, 156 Weeks ]
• Change from Baseline in Systolic Blood Pressure (SBP) in Millimeter Mercury (mmHg) [ Time Frame: Baseline, 156 Weeks ]
• Change from Baseline Diastolic Blood Pressure (DBP) (mmHg) [ Time Frame: Baseline, 156 Weeks ]
• Percentage of Participants with Hemoglobin A1c (HbA1c) <39 Millimole/Mole (mmol/mol) (5.7%) [ Time Frame: Up to 5 Years ]
  Percentage of participants with HbA1c <39 mmol/mol (5.7%) at each time where HbA1c is assessed for participants with a screening HbA1c ≥39 mmol/mol.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Tirzepatide (LY3298176) on the Reduction on Morbidity and Mortality in Adults With Obesity
• Official Title: A Phase 3, Randomized, Double-blind, Placebo-Controlled Study to Investigate the Effect of Tirzepatide on the Reduction of Morbidity and Mortality in Adults With Obesity
• Brief Summary: This study will investigate the effect of tirzepatide on the reduction of morbidity and mortality in adults living with obesity and provide additional evidence for the potential clinical benefits of tirzepatide in this population.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Obesity
• Overweight

Intervention

• Drug: Tirzepatide
  Administered SC
  Other Name: LY3298176
• Drug: Placebo
  Administered SC

Study Arms

• Experimental: Tirzepatide
  Participants will receive escalated doses of tirzepatide subcutaneously (SC) up to a maximum tolerated dose.
  Intervention: Drug: Tirzepatide
• Placebo Comparator: Placebo
  Participants will receive tirzepatide matched placebo.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 15, 2024): 15374
• Original Estimated Enrollment (submitted: September 22, 2022): 15000
• Estimated Study Completion Date: October 7, 2027
• Estimated Primary Completion Date: October 7, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have a body mass index (BMI) ≥27.0 kilogram/square meter (kg/m ²)

• Are either

  • individuals ≥40 years of age with established cardiovascular disease (CVD).

    • CVD is defined as meeting at least one of the following:

      • Coronary artery disease
      • Cerebrovascular disease
    • Peripheral arterial disease OR

    • individuals without established CVD but have the presence of cardiovascular (CV) risk factors (primary prevention)

      • women 55-69 years of age or men 50-64 years of age with at least 3 risk factors like tobacco use, dyslipidemia, hypertension at screening, or
      • women ≥70 years of age or men, ≥65 years of age with at least 2 risk factors at screening.

Exclusion Criteria:

• Have type 1 diabetes (T1D) or (T2D), history of ketoacidosis, or hyperosmolar state/coma
• Have laboratory evidence diagnostic of diabetes mellitus at screening of HbA1c ≥6.5% (≥48 millimole/mole (mmol/mol) or fasting glucose (FG) ≥126 milligram/deciliter (≥7.0 millimole/liter (mmol/L).

• Any one of the following CV conditions within 90 days prior to screening

  • MI
  • acute coronary syndrome
  • stroke
  • coronary or peripheral arterial revascularization procedure, which may also include carotid artery revascularization, or
  • acute decompensated heart failure
• Have a known clinically significant gastric emptying abnormality such as severe gastroparesis or gastric outlet obstruction or have undergone or currently planning any gastric bypass (metabolic) surgery or restrictive bariatric surgery. Note: Liposuction or abdominoplasty are not considered as gastric bypass procedures.
• Have a history of chronic or acute pancreatitis
• Have a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.
• Have acute or chronic hepatitis, or clinical signs or symptoms of any other liver disease, or have elevated liver enzyme measurements, determined by the central laboratory at screening
• Have a presence or history of malignant neoplasms within the past 5 years prior to screening.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Puerto Rico, Romania, Slovakia, Spain, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05556512
• Other Study ID Numbers: 17253; I8F-MC-GPIJ ( Other Identifier: Eli Lilly and Company ); 2022-501744-15-00 ( Other Identifier: EU Clinical Trial Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: http://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: April 2024