A Study of Remternetug (LY3372993) in Participants With Alzheimer's Disease (TRAILRUNNER-ALZ 1)

Assessment of Safety, Tolerability, and Efficacy Measured by Amyloid Reduction of LY3372993 in Early Symptomatic Alzheimer's Disease

The reason for this study is to collect safety and efficacy information regarding the study drug remternetug in participants with early symptomatic Alzheimer's disease (AD).

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Remternetug (IV); Drug: Remternetug (SC); Drug: Placebo

Detailed Description

TRAILRUNNER-ALZ 1 is a Phase 3, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of remternetug in participants with early symptomatic AD. Initially, 600 participants will enroll in the double-blind treatment period. Participants in the double-blind treatment period will receive remternetug or placebo administered via subcutaneous injection or intravenous infusion.

Following the 52-week main study period, participants will continue participation for up to an additional 76 weeks in an extension period. Participants who previously received remternetug will receive placebo and participants who previously received placebo will receive remternetug. Thus, all participants will receive remternetug if they complete the study.

An additional 974 participants with early Alzheimer's disease will be enrolled to an addendum safety cohort. The participants will be administered open label remternetug via subcutaneous injection or intravenous infusion. Participants enrolled into the addendum safety cohort are not eligible for the extension period.

• Study Type: Interventional
• Enrollment (Actual): 1667
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Ibaraki
    • Toride, Ibaraki, Japan, 302-0004
      • Memory Clinic Toride
  • Okayama-ken
    • Kurashiki, Okayama-ken, Japan, 710-0813
      • Katayama Medical Clinic
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-0034
      • Memory Clinic Ochanomizu
• United States
  • Arizona
    • Chandler, Arizona, United States, 85286
      • MD First Research - Chandler
  • California
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research, Inc.
    • Carlsbad, California, United States, 92011
      • North County Neurology Associates
    • Encino, California, United States, 91316
      • Wr- Pri, Llc
    • Fresno, California, United States, 93710
      • Neuro-Pain Medical Center
    • Irvine, California, United States, 92614
      • Irvine Clinical Research
    • La Jolla, California, United States, 92037
      • Kaizen Brain Center
    • Redlands, California, United States, 92374
      • Anderson Clinical Research
  • Colorado
    • Basalt, Colorado, United States, 81621
      • Mountain Neurological Research Center
    • Boulder, Colorado, United States, 80301
      • Alpine Clinical Research Center
    • Colorado Springs, Colorado, United States, 80907
      • Colorado Springs Neurological Associates
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Institute for Neurodegenerative Disorders
    • Stamford, Connecticut, United States, 06905
      • Ki Health Partners, LLc, dba New England Institute for Clinical Research
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Aventura, Florida, United States, 33180
      • VIN-Julie Schwartzbard
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Fort Myers, Florida, United States, 33912
      • Neuropsychiatric Research Center of Southwest Florida
    • Greenacres City, Florida, United States, 33467
      • Finlay Medical Research
    • Jacksonville, Florida, United States, 32216
      • Encore Research Group- Jacksonville Center for Clinical Research
    • Maitland, Florida, United States, 32751
      • K2 Medical Research
    • Maitland, Florida, United States, 32751
      • ClinCloud - Maitland
    • Melbourne, Florida, United States, 32940
      • ClinCloud - Viera
    • Merritt Island, Florida, United States, 32952
      • Merritt Island Medical Research, LLC
    • Miami, Florida, United States, 33135
      • Optimus U Corporation
    • Miami, Florida, United States, 33133
      • VIN-Andrew Lerman
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Orlando, Florida, United States, 32803
      • Charter Research - Winter Park
    • Pensacola, Florida, United States, 32504
      • Emerald Coast Neurology - Airport Boulevard
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Stuart, Florida, United States, 34997
      • Brain Matters Research
    • Stuart, Florida, United States, 34997
      • Alzheimer's Research and Treatment Center
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Neurological Clinic
    • The Villages, Florida, United States, 32162
      • Charter Research - Lady Lake
    • Wellington, Florida, United States, 33414
      • Alzheimer's Research and Treatment Center
    • West Palm Beach, Florida, United States, 33407
      • Palm Beach Neurology
    • Winter Park, Florida, United States, 32789
      • Conquest Research
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Columbus Memory Center, PC
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials - Andersonville
    • Elk Grove Village, Illinois, United States, 60007
      • AMITA Health - Alexian Brothers Neurosciences Institute Clinical Research
  • Iowa
    • Waterloo, Iowa, United States, 50702
      • Covenant Medical Center
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinical Research Center - Central Office
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Care Access - Lake Charles
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451
      • MedVadis Research Corporation
    • Watertown, Massachusetts, United States, 02472
      • Adams Clinical
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Citizens Memorial Hospital District
    • Chesterfield, Missouri, United States, 63005
      • Clinical Research Professionals
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Las Vegas Medical Research
  • New Jersey
    • Springfield, New Jersey, United States, 07081
      • The Cognitive and Research Center of New Jersey
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research Institute of New Jersey
  • New York
    • Albany, New York, United States, 12208
      • Neurological Associates Albany
  • North Carolina
    • Matthews, North Carolina, United States, 28105
      • AMC Research
    • Morehead City, North Carolina, United States, 28557
      • Carteret Medical Group
  • Ohio
    • Canton, Ohio, United States, 44718
      • NeuroScience Research Center
    • Centerville, Ohio, United States, 45459
      • Valley Medical Research
    • Dayton, Ohio, United States, 45459
      • Neurology Diagnostics, Inc.
  • Oregon
    • Portland, Oregon, United States, 97225
      • Center for Cognitive Health
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
      • The Clinical Trial Center, LLC
    • Plymouth Meeting, Pennsylvania, United States, 19462
      • Keystone Clinical Studies
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Rhode Island Mood & Memory Research Institute
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, P.C.
  • Texas
    • Austin, Texas, United States, 78749
      • Texas Diabetes & Endocrinology, P.A.
    • Beaumont, Texas, United States, 77702
      • Gadolin Research
    • Dallas, Texas, United States, 75231
      • Kerwin Medical Center
    • Dallas, Texas, United States, 75243
      • Neurology Consultants of Dallas, PA
    • Houston, Texas, United States, 77054
      • The University of Texas Health Science Center at Houston
    • Round Rock, Texas, United States, 78681
      • Central Texas Neurology Consultants
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research, LLC
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Re:Cognition Health
    • Richmond, Virginia, United States, 23294
      • National Clinical Research, Inc
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Tacoma, Washington, United States, 98405
      • Universal Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Gradual and progressive change in cognitive function ≥6 months prior to screening.
• A Mini-Mental (MMSE) score of 20 to 30 (inclusive) at screening.
• Has an amyloid PET scan result consistent with the eligibility criteria.
• Have a reliable study partner who will provide written informed consent to participate and is in frequent contact with the participant.
• Have adequate literacy, vision, and hearing for the neuropsychological testing in the opinion of the investigator at the time of screening.
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.
• Males and females will be eligible for this study.
• Women not of childbearing potential (WNOCBP) may participate in this trial.

Exclusion Criteria:

• Current serious or unstable illnesses that, in the investigator's opinion, could interfere with the analyses in this study; or has a life expectancy of <24 months.
• History of cancer with high risk of recurrence and preventing completion of the trial.
• Participants with any current primary psychiatric diagnosis other than AD that in the investigator's opinion, is likely to confound interpretation of the drug effect, affect cognitive assessment, or affect the participant's ability to complete the study.
• History of clinically significant multiple or severe drug allergies.
• Have any clinically important abnormality at screening, as determined by investigator that could be detrimental to the participant, could compromise the study, or show evidence of other etiologies for dementia.
• Screening magnetic resonance imaging (MRI) which shows evidence of significant abnormality that would suggest another potential etiology for progressive dementia or a clinically significant finding that may impact the participant's ability to safely participate in the study.
• Have any contraindications for MRI or positron emission tomography (PET).
• Have had prior treatment with a passive anti-amyloid immunotherapy.
• Have received active immunization against Aβ in any other study.
• Have known allergies to remternetug related compounds, or any components of the formulation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remternetug (IV); Participants will receive remternetug intravenously (IV) Participants will receive remternetug IV during the treatment period, then switch to placebo IV in the extension period.	Drug: Remternetug (IV); Administered IV; Other Names: LY3372993
Experimental: Remternetug (SC); Participants will receive one of two dosing regimens of remternetug subcutaneously (SC) Participants will receive remternetug SC during the treatment period, then switch to placebo SC in the extension period.	Drug: Remternetug (SC); Administered SC; Other Names: LY3372993
Placebo Comparator: Placebo; Participants will receive placebo matching remternetug IV or SC. Participants will receive placebo IV during the treatment period, then switch to remternetug IV in the extension period. Participants will receive placebo SC during the treatment period, then switch to LY3372993 SC in the extension period.	Drug: Placebo; Administered IV or SC
Experimental: Open-Label Addenda Remternetug (IV); Participants will receive one of six dosing regimens of remternetug IV during the open-label addenda.	Drug: Remternetug (IV); Administered IV; Other Names: LY3372993
Experimental: Open-Label Addenda Remternetug (SC); Participants will receive one of nine dosing regimens of remternetug SC during the open-label addenda.	Drug: Remternetug (SC); Administered SC; Other Names: LY3372993

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Who Reach Amyloid Plaque Clearance on Amyloid PET Scan for Remternetug versus Placebo	Week 52

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean Absolute Change from Baseline in Brain Amyloid Plaque on Amyloid PET Scan for Remternetug versus Placebo	Baseline, Week 52
Percentage of Participants Who Reach Amyloid Plaque Clearance on Amyloid PET Scan for Remternetug versus Placebo	Week 24
Mean Absolute Change from Baseline in Brain Amyloid Plaque on Amyloid PET Scan for Remternetug versus Placebo	Baseline, Week 24
Time to Reach Complete Amyloid Plaque Clearance on Remternetug versus Placebo	Up to Week 52
Pharmacokinetics (PK) Observed Trough Serum Concentration (Cmin) of Remternetug	Baseline to Week 52
Number of Participants with Treatment Emergent Anti-Drug Antibodies (TE-ADAs)	Baseline to Week 52

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• 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

Publications and helpful links

Helpful Links

• A Study of Remternetug (LY3372993) in Participants With Alzheimer's Disease (TRAILRUNNER-ALZ 1)

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Actual): April 24, 2024
• Study Completion (Actual): May 12, 2026

Study Registration Dates

• First Submitted: July 14, 2022
• First Submitted That Met QC Criteria: July 15, 2022
• First Posted (Actual): July 19, 2022

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Dementia; Mild cognitive impairment; Amyloid-beta therapy; Amyloid Plaque; Disease modifying
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathological Conditions, Anatomical; Neurocognitive Disorders; Cognition Disorders; Tauopathies; Neurodegenerative Diseases; Pathological Conditions, Signs and Symptoms; Cognitive Dysfunction; Alzheimer Disease; Dementia; Plaque, Amyloid
• Other Study ID Numbers: 18467; J1G-MC-LAKC (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing 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
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• 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.: No