Donanemab for Early Alzheimer's Disease

Recruiting at 66 trial locations

Overseen By Jeffrey A Norton

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Anti-amyloid immunotherapy

Disqualifiers: Neurological disease, Serious illnesses, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

Duration: 12-24 weeks

1100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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 different doses of donanemab, a drug aimed at helping people with early Alzheimer's disease. Donanemab has shown rapid reduction of brain amyloid in early Alzheimer's disease. The study will look at how often and how severely participants experience a side effect involving brain swelling. Researchers also want to find out which patient characteristics might predict this side effect.

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 adults with early symptomatic Alzheimer's who have had memory issues for over 6 months, confirmed amyloid pathology in the brain, and a certain score on a mental state exam. People with serious illnesses, cancer within the last 5 years, life expectancy under 2 years, or significant neurological diseases other than Alzheimer's can't join.

Inclusion Criteria

My memory has been getting worse for 6 months or more.

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

I have had cancer or a tumor in the last 5 years.

I have had skin, cervical, or prostate cancer but they were early stage and low risk.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive different donanemab dosing regimens by IV infusion, with placebo at certain intervals to preserve the blind

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on ARIA-E frequency and severity

4-8 weeks

Treatment Details

Interventions

• Donanemab

Trial Overview The study tests different doses of Donanemab to see how they affect brain swelling (ARIA-E) in people with early Alzheimer's. It also looks at whether certain characteristics predict ARIA risk. Participants will either receive Donanemab or a placebo.

Participant Groups

Group I: Donanemab Dose Level 4 Experimental Treatment 2 Interventions

Participants will receive donanemab by IV infusion. Participants will receive placebo at certain intervals to preserve the blind.

Group II: Donanemab Dose Level 3 Experimental Treatment 2 Interventions

Participants will receive donanemab by IV infusion. Participants will receive placebo at certain intervals to preserve the blind.

Group III: Donanemab Dose Level 2 Experimental Treatment 2 Interventions

Participants will receive donanemab by IV infusion. Participants will receive placebo at certain intervals to preserve the blind.

Group IV: Donanemab Dose Level 1 Experimental Treatment 2 Interventions

Participants will receive donanemab by intravenously (IV) infusion. Participants will receive placebo at certain intervals to preserve the blind.

Group V: Donanemab Addendum Arm 2 Experimental Treatment 2 Interventions

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

Group VI: Donanemab Addendum Arm 1 Experimental Treatment 2 Interventions

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

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]