The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Renal Function in Adults Living With Obesity (TRIUMPH-OUTCOMES)

• ClinicalTrials.gov Identifier: NCT06383390
• Recruitment Status: Not yet recruiting
• First Posted: April 25, 2024
• Last Update Posted: April 25, 2024
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: April 22, 2024
• First Posted Date: April 25, 2024
• Last Update Posted Date: April 25, 2024
• Estimated Study Start Date: May 2024
• Estimated Primary Completion Date: February 2029 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 22, 2024)

• Time to First Occurrence of Composite Endpoints [ Time Frame: Randomization up to Study Completion (Approximate 248 Weeks) ]
  A composite endpoint includes nonfatal myocardial infarction (MI), nonfatal stroke, cardiovascular (CV) death, or hospitalization or urgent visit due to heart failure (HF).
• Time to First Occurrence of Composite Endpoint of End Stage Kidney Disease (ESKD), ≥ 40% Sustained Decline in Estimated Glomerular Filtration Rate (eGFR), CV Death or Renal Death [ Time Frame: Randomization up to Study Completion (Approximate 248 Weeks) ]
  ESKD is defined as the following individual components: persistent eGFR <15 mL/min/1.73 m^2 confirmed by a second measurement at the earliest 4 weeks after the initial measurement at the central laboratory, initiation of dialysis for at least 30 days, receiving a kidney transplant. Sustained decline in eGFR (≥40%) will be confirmed by a repeated measure 1 month after the initial result.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: April 22, 2024)

• Time to First Occurrence of Composite Endpoint of Major Cardiovascular Events (MACE-3) [ Time Frame: Randomization up to Study Completion (Approximate 248 Weeks) ]
  MACE-3 includes CV death, nonfatal MI, and nonfatal stroke.
• Time to First Occurrence of Composite Endpoint of CV death, or hospitalization or urgent visit due to HF [ Time Frame: Randomization up to Study Completion (Approximate 248 Weeks) ]
  Time to First Occurrence of Composite Endpoint of CV death, or hospitalization or urgent visit due to HF.
• Time to Occurrence of All-Cause Death [ Time Frame: Randomization up to Study Completion (Approximate 248 Weeks) ]
  Time to all-cause death.
• Time to First Occurrence of composite endpoint of ≥ 40% Sustained Decline in eGFR, End-Stage Renal Disease (ESRD), or Renal Death [ Time Frame: Randomization up to Study Completion (Approximate 248 Weeks) ]
• Percentage change from Baseline in Albuminuria urinary albumin/creatinine ratio (UACR) in Participants with UACR ≥30 mg/g (0.03 mg/mg) at baseline [ Time Frame: Randomization up to Study Completion (Approximate 248 Weeks) ]

• 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: The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Renal Function in Adults Living With Obesity (TRIUMPH-OUTCOMES)
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Event-Driven Study to Investigate the Effect of Retatrutide on the Incidence of Major Adverse Cardiovascular Events and the Decline in Kidney Function in Participants With Body Mass Index ≥27 kg/m^2 and Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease.
• Brief Summary: The main purpose of this study is to determine if retatrutide can significantly lower the incidence of serious heart-related complications or prevent the worsening of kidney function. The trial will enroll adults with body mass index 27 kg/m^2 or higher and Atherosclerotic Cardiovascular Disease and/or chronic kidney disease.
• 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: Overweight and Obesity

Intervention

• Drug: Retatrutide
  Administered SC
  Other Name: LY3437943
• Drug: Placebo
  Administered SC

Study Arms

• Experimental: Retatrutide
  Participants will receive escalated doses of retatrutide administered subcutaneously (SC) up to a maximum tolerated dose.
  Intervention: Drug: Retatrutide
• Placebo Comparator: Placebo
  Participants will receive matching placebo administered SC.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: April 22, 2024): 10000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2029
• Estimated Primary Completion Date: February 2029 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• A Body Mass Index of ≥27.0 kilograms per meter squared (kg/m^2)
• Participants may be with or without type 2 diabetes (T2D) unless their hemoglobin A1c (HbA1c) is 10% or lower

• Participants have established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD), as evidenced at least one of the following:

  • Coronary artery disease
  • Cerebrovascular disease
  • Peripheral arterial disease

  • Chronic kidney disease defined as:

    • eGFR <45 millilitres/minute/1.73 meter squared (mL/min/1.73m^2) and UACR >30 milligram/gram (mg/g)
    • eGFR <60 mL/min/1.73 m^2 and UACR >100 mg/g, or
    • eGFR <75 mL/min/1.73 m^2 and UACR >300 mg/g (eGFR is calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin c equation as determined by central lab)

Exclusion Criteria:

Diabetes related:

• Participants have Type 1 Diabetes or history of diabetic ketoacidosis

CV related:

• Participants have any of the following cardiovascular conditions ≤ 90 days prior to randomization:

  • Myocardial infarction
  • Acute coronary syndrome
  • Stroke, or
  • Coronary, peripheral, or carotid artery arterial revascularization procedure.
• Have acute decompensated heart failure requiring hospitalization.
• Have New York Heart Association (NYHA) Classification Class IV heart failure at screening

Kidney related:

• Participants have an eGFR <20 mL/min/1.73 m^2 at screening
• Have UACR >5000 mg/g at screening
• Have received any form of dialysis ≤ 90 days from the date of randomization
• Have either undergone a kidney transplant or have a transplant procedure scheduled

Other medical conditions:

• Participants have had or plan to have a surgical treatment for obesity,
• Have a history of chronic or acute pancreatitis
• Have a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) syndrome type 2
• Have a known clinically significant gastric emptying abnormality, such as severe gastroparesis or gastric outlet obstruction

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 45 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; 1-317-615-4559; ClinicalTrials.gov@lilly.com

• Listed Location Countries: Argentina, Australia, Austria, Brazil, Canada, Czechia, Denmark, France, Germany, Hungary, India, Israel, Mexico, Netherlands, Poland, Puerto Rico, Slovakia, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT06383390
• Other Study ID Numbers: 18584; J1I-MC-GZBO ( Other Identifier: Eli Lilly and Company ); 2023-508630-34-00 ( Other Identifier: EU CTR 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
• Product Manufactured in and Exported from the U.S.: Yes

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 European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: 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