Donanemab for Early Alzheimer's Disease

Recruiting at 428 trial locations

Overseen By Jeffrey S. Ross

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Immunoglobulin G therapy

Disqualifiers: MRI/PET contraindication, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 76 weeks

1736 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently receiving immunoglobulin G (IgG) therapy.

Is donanemab safe for humans?

Donanemab has been studied for safety in people with Alzheimer's disease, but the FDA rejected its accelerated approval due to inadequate safety data. Some studies noted amyloid-related imaging abnormalities with edema or effusions (ARIA-E), which are changes in the brain that can occur with this treatment. ^{1 2 3 4 5}

How is the drug donanemab different from other Alzheimer's treatments?

Donanemab is unique because it is a monoclonal antibody that specifically targets a modified form of amyloid-beta called pyroglutamate amyloid-peptide, which is found in the brain plaques associated with Alzheimer's disease. This targeted approach aims to reduce these plaques more effectively than other treatments. ^{1 2 4 6 7}

What is the purpose of this trial?

This trial is testing donanemab, a drug for early Alzheimer's disease. It targets people with early symptoms and specific brain changes. The drug helps remove harmful proteins from the brain, potentially slowing down or improving symptoms.

Research Team

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)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for people with early Alzheimer's who've had memory changes for at least 6 months, scoring 20-28 on the MMSE (a cognitive test). They must meet specific criteria on PET scans and have a partner to consent to participate. Those who can't undergo MRI or PET scans or are currently on IgG therapy cannot join.

Inclusion Criteria

You need to have a specific type of PET scan that meets certain criteria. This does not apply to the safety group.

You scored between 20 and 28 on a memory and thinking test at the beginning of the study.

My memory has been getting worse for at least 6 months.

Exclusion Criteria

You cannot have MRI or PET scans for medical reasons.

I am currently receiving IgG therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive donanemab or placebo intravenously every 4 weeks for up to 72 weeks

76 weeks

Every 4 weeks (in-person)

Long-term Extension

A double-blind 78-week extension period to further evaluate donanemab efficacy and safety

78 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Donanemab

Trial Overview The study is testing the safety and effectiveness of Donanemab in treating early Alzheimer's disease. Participants will either receive Donanemab or a placebo. An additional group will be openly given Donanemab to assess its safety further.

Participant Groups

Group I: Donanemab Experimental Treatment 1 Intervention

Participants received 700 milligram (mg) Donanemab every 4 weeks (Q4W) x 3 doses, then 1400 mg Q4W given intravenously (IV) for up to 72 weeks

Group II: Placebo Placebo Group 1 Intervention

Participants received placebo given IV.

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

Donanemab, administered at a dose of 10 mg/kg, was generally well tolerated in patients with mild cognitive impairment or mild to moderate Alzheimer's disease, showing a significant reduction of amyloid deposits by 40% to 50%.

Despite a shorter than expected half-life of approximately 10 days at the highest dose, about 90% of subjects developed anti-drug antibodies within 3 months, indicating a robust immune response to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donanemab (LY3002813) dose-escalation study in Alzheimer's disease. Lowe, SL., Willis, BA., Hawdon, A., et al.[2022]

In the phase 2 TRAILBLAZER-ALZ trial, donanemab reduced amyloid plaques in the brains of participants with early symptomatic Alzheimer's disease but did not significantly improve cognitive function or daily living activities, with a p-value of 0.04 indicating only marginal improvement.

The study found that while donanemab effectively targeted amyloid plaques, it did not affect tau load, which may be a key biomarker for cognitive decline, suggesting that simply removing amyloid plaques may not be sufficient to enhance cognitive outcomes in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Still grasping at straws: donanemab in Alzheimer's disease. Doggrell, SA.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Donanemab (LY3002813) dose-escalation study in Alzheimer's disease. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Evidences and therapeutic advantages of donanemab in the treatment of early Alzheimer's disease. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Donanemab for Alzheimer's Disease: A Systematic Review of Clinical Trials. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Donanemab (LY3002813) Phase 1b Study in Alzheimer's Disease: Rapid and Sustained Reduction of Brain Amyloid Measured by Florbetapir F18 Imaging. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Donanemab Population Pharmacokinetics, Amyloid Plaque Reduction, and Safety in Participants with Alzheimer's Disease. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Donanemab in Early Alzheimer's Disease. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Still grasping at straws: donanemab in Alzheimer's disease. [2022]