Investigating the Effect of Different Donanemab Dosing Regimens on ARIA-E and Amyloid Lowering in Adults With Early Symptomatic Alzheimer's Disease

Official Summary

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.

Eligibility Requirements

• Minimum Age: 60 Years
• Maximum Age: 85 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 1,175 participants

Study Arms

• 1400 mg Donanemab - Standard Regimen (EXPERIMENTAL)
  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.
• 1400 mg Donanemab - Dose Skipping (EXPERIMENTAL)
  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.
• 1400 mg Donanemab - Titration (EXPERIMENTAL)
  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.
• 1400 mg Donanemab - Maximum Concentration (Cmax) (EXPERIMENTAL)
  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.
• Donanemab Addendum Arm 1 (EXPERIMENTAL)
  Participants will receive donanemab by IV infusion. Participants will receive placebo pretreatment to preserve the blind prior to donanemab infusion.
• Donanemab Addendum Arm 2 (EXPERIMENTAL)
  Participants will receive donanemab by IV infusion. Participants will receive dexamethasone pretreatment prior to donanemab infusion

Interventions

• DRUG: Donanemab — Administered IV
• DRUG: Placebo — Administered IV
• DRUG: Dexamethasone — Administered IV

Primary Outcomes

• Percentage of Participants With Any Occurrence of Amyloid-Related Imaging Abnormality-Edema/Effusion (ARIA-E) (24 Weeks)

Secondary Outcomes

• Percentage of Participants With Any Occurrence of ARIA-E (52 Weeks)
• Change From Baseline in Brain Amyloid Plaque Deposition As Measured By Amyloid Positron Emission Tomography (PET) Scan (Baseline, 76 Weeks)
• Percentage of Participants With Any Occurrence of Amyloid-Related Imaging Abnormality-Hemorrhage/Hemosiderin Deposits (ARIA-H) (24 Weeks)
• Percentage of Participants With ARIA-H (52 Weeks)
• Percentage of Participants With Maximum Severity of ARIA-E or ARIA-H (76 Weeks)

Eligibility Criteria

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 Locations

• MD First Research - Chandler, Chandler, Arizona, United States
• Irvine Clinical Research, Irvine, California, United States
• Healthy Brain Clinic, Long Beach, California, United States
• California Neuroscience Research Medical Group, Inc., Sherman Oaks, California, United States
• JEM Research Institute, Atlantis, Florida, United States
• VIN-Julie Schwartzbard, Aventura, Florida, United States
• Excel Medical Clinical Trials, Boca Raton, Florida, United States
• K2 Medical Research, Clermont, Florida, United States
• Brain Matters Research, Delray Beach, Florida, United States
• Neuropsychiatric Research Center of Southwest Florida, Fort Myers, Florida, United States
• ...and 10 more locations

Study Officials

• 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) — STUDY_DIRECTOR
  Eli Lilly and Company

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