A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults With Early Alzheimer's Disease (TRAILBLAZER-ALZ 6)

Lilly

Status and phase: Active, not recruiting; Phase 3

Conditions: Alzheimer's Disease; Mental Disorders; Neurodegenerative Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Dementia; Brain Diseases

Treatments: Drug: Dexamethasone; Drug: Placebo; Drug: Donanemab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05738486

U1111-1285-9438 (Other Identifier)

2022-502268-18-00 (Other Identifier)

I5T-MC-AACQ (Other Identifier)

18648

Details and patient eligibility

About

This study will investigate different donanemab dosing regimens and their effect on the frequency and severity of ARIA-E in adults with early symptomatic Alzheimer's disease (AD) and explore participant characteristics that might predict risk of ARIA.

Approximately 375 additional participants will be enrolled per addendum.

The study will last approximately 91 weeks and include up to 26 visits in the main study.

Enrollment: 1,175 patients

Sex: All

Ages: 60 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Gradual and progressive change in memory function reported by the participant or informant for ≥6 months.
• A mini mental state examination (MMSE) score of 20 to 28 (inclusive) at screening.
• Have an amyloid PET scan result from central read, consistent with the presence of amyloid pathology.

Exclusion criteria

• Have significant neurological disease affecting the central nervous system other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson's disease, multiple concussions, or epilepsy or recurrent seizures, except febrile childhood seizures.
• Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses in this study.
• A life expectancy of <24 months.
• Contraindication to MRI or PET scans
• Have had prior treatment with a passive anti-amyloid immunotherapy.
• Have a presence or history of malignant neoplasms within the past 5 years prior to Visit 1.

Exceptions:

• non-metastatic basal- or squamous-cell skin cancer
• Stage 0 non-invasive carcinoma of the cervix
• Stage 0 non-invasive prostate cancer, or
• other cancers with low risk of recurrence or spread

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,175 participants in 6 patient groups

1400 mg Donanemab - Standard Regimen

Experimental group

Description:

Participants received: * 700 milligrams (mg) donanemab administered intravenously (IV) at baseline, week 4, and 8. * placebo administered IV at week 2, 6, 10, and 14. * 1400 mg of donanemab administered IV at week 12, 16, 20, and 24.

Treatment:

Drug: Donanemab

Drug: Placebo

1400 mg Donanemab - Dose Skipping

Experimental group

Description:

Participants received: * 700 mg donanemab administered IV at baseline. * placebo administered IV at week 2, 4, 6, 10, and 14. * 1400 mg of donanemab administered IV at week 8, 12, 16, 20, and 24.

Treatment:

Drug: Donanemab

Drug: Placebo

1400 mg Donanemab - Titration

Experimental group

Description:

Participants received: * 350 mg donanemab administered IV at baseline. * placebo administered IV at week 2, 6, 10, and 14. * 700 mg donanemab administered IV at week 4. * 1050 mg of donanemab administered IV at week 8. * 1400 mg of donanemab administered IV at week 12, 16, 20, and 24.

Treatment:

Drug: Donanemab

Drug: Placebo

1400 mg Donanemab - Maximum Concentration (Cmax)

Experimental group

Description:

Participants received: * 350 mg donanemab administered IV at baseline, weeks 2, 4, 6, 8, and 10. * 700 mg donanemab administered IV at weeks 12 and 14. * 1400 mg of donanemab administered IV at weeks 16, 20, and 24.

Treatment:

Drug: Donanemab

Drug: Placebo

Donanemab Addendum Arm 1

Experimental group

Description:

Participants will receive donanemab by IV infusion. Participants will receive placebo pretreatment to preserve the blind prior to donanemab infusion.

Treatment:

Drug: Donanemab

Drug: Placebo

Donanemab Addendum Arm 2

Experimental group

Description:

Participants will receive donanemab by IV infusion. Participants will receive dexamethasone pretreatment prior to donanemab infusion

Treatment:

Drug: Donanemab

Drug: Dexamethasone