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

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

Detailed Description
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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 enrollin 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 52 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 640 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.

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

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Remternetug (IV)
* Drug: Remternetug (SC)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gradual and progressive change in cognitive function ≥6 months prior to screening. A Mini-Mental (MMSE) score of 20 to 28 (inclusive) at screening. Has a P-tau result consistent with the presence of amyloid pathology. Has an amyloid PET scan result consistent with the presence of brain amyloid pathology. 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: Significant neurological disease affecting the central nervous system (CNS) other than AD, that may affect cognition or ability to complete the study. 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 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 that is <5 half-lives prior to randomization. Have received active immunization against Aβ in any other study. Have known allergies to remternetug related compounds, or any components of the formulation.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remternetug (IV)<br>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)<br>* Administered IV<br>* Other names: LY3372993;|
| Experimental: Remternetug (SC)<br>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)<br>* Administered SC<br>* Other names: LY3372993;|
| Placebo Comparator: Placebo<br>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<br>* Administered IV or SC<br>|
| Experimental: Open-Label Addenda Remternetug (IV)<br>Participants will receive one of three dosing regimens of remternetug IV during the open-label addenda. | Drug: Remternetug (IV)<br>* Administered IV<br>* Other names: LY3372993;|
| Experimental: Open-Label Addenda Remternetug (SC)<br>Participants will receive one of two dosing regimens of remternetug SC during the open-label addenda. | Drug: Remternetug (SC)<br>* Administered SC<br>* Other names: LY3372993;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild cognitive impairment, Alzheimer's disease, Dementia, Amyloid-beta therapy, Amyloid Plaque, Disease modifying