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

Lilly

Status and phase: Enrolling; Phase 3

Conditions: Alzheimer's Disease

Treatments: Drug: Remternetug (SC); Drug: Placebo; Drug: Remternetug (IV)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05463731

J1G-MC-LAKC (Other Identifier)

18467

Details and patient eligibility

About

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).

Full 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 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.

Enrollment: 600 estimated patients

Sex: All

Ages: 60 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

600 participants in 5 patient groups, including a placebo group

Remternetug (IV)

Experimental group

Description:

Participants will receive remternetug intravenously (IV) Participants will receive remternetug IV during the treatment period, then switch to placebo IV in the extension period.

Treatment:

Drug: Remternetug (IV)

Remternetug (SC)

Experimental group

Description:

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.

Treatment:

Drug: Remternetug (SC)

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Open-Label Addenda Remternetug (IV)

Experimental group

Description:

Participants will receive one of three dosing regimens of remternetug IV during the open-label addenda.

Treatment:

Drug: Remternetug (IV)

Open-Label Addenda Remternetug (SC)

Experimental group

Description:

Participants will receive one of two dosing regimens of remternetug SC during the open-label addenda.

Treatment:

Drug: Remternetug (SC)