Donanemab for Early Alzheimer's Disease

Not currently recruiting at 445 trial locations

Overseen By Peter McAllister

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of donanemab for people with early Alzheimer's disease. Donanemab, an experimental treatment administered through an IV, aims to slow memory loss and cognitive decline. Participants will receive either donanemab or a placebo (a non-active substance) to compare effects. The trial suits individuals who have experienced gradual memory changes over at least six months and can have a partner join them in the study process. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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 there any evidence suggesting that donanemab is likely to be safe for humans?

Research shows that donanemab is generally well-tolerated by people with early Alzheimer's disease. In earlier studies, donanemab slowed the disease's progression more effectively than a placebo, which contains no active drug. Some side effects were reported, mostly mild, such as injection site reactions and headaches. Serious side effects were rare.

Since this trial is in a more advanced stage, strong evidence already supports donanemab's safety for humans. It has been tested in many people, and its safety is well understood. However, like any medication, there is always a risk of side effects. Researchers will closely monitor participants in this trial to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Donanemab is unique because it targets amyloid-beta plaques in the brain, which are thought to play a critical role in the development of Alzheimer's disease. Unlike traditional treatments that primarily manage symptoms, Donanemab aims to address the root cause by clearing these plaques. Researchers are excited about this treatment because its targeted approach could potentially slow down or alter the progression of early Alzheimer's, offering hope for more effective management of the disease.

What evidence suggests that donanemab might be an effective treatment for early Alzheimer's disease?

Research has shown that donanemab, which participants in this trial may receive, may help treat early Alzheimer's disease. One study found that donanemab improved memory and daily living skills in patients. In another study, 52% of patients with low to medium levels of tau proteins, linked to Alzheimer's, showed positive results after a year of treatment. Donanemab also slowed cognitive decline by 32%, based on a score measuring thinking and daily functioning. These findings suggest that donanemab might slow the progression of early Alzheimer's disease. ^{1 2 6 7 8}

Who Is on the 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

Are You a Good Fit for This Trial?

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.

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

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

Exclusion Criteria

You cannot have MRI or PET scans for medical reasons.

I am currently receiving IgG therapy.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2807533

Trial of Donanemab in Early Symptomatic Alzheimer Disease These clinical outcomes were achieved in 52% of low/medium tau participants completing donanemab treatment by 1 year, based on when a ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37459141/

Donanemab in Early Symptomatic Alzheimer Disease - PubMed Of the 24 gated outcomes, 23 were statistically significant. The least-squares mean (LSM) change in iADRS score at 76 weeks was -6.02 (95% CI, - ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2100708

Donanemab in Early Alzheimer's Disease In patients with early Alzheimer's disease, donanemab resulted in a better composite score for cognition and for the ability to perform ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12040886/

Re-evaluation of the efficacy and safety of anti-Aβ monoclonal ... Lecanemab/Donanemab can improve memory, cognitive function, and daily living abilities in patients with early AD, significantly reduce the composite score of ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2274580725000949

Donanemab: Appropriate use recommendations Treatment with donanemab was associated with 32 % slowing of decline on the primary clinical endpoint, the Integrated Alzheimer's Disease Rating Scale (iADRS). ...

6. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2839837

Posttreatment Amyloid Levels and Clinical Outcomes ... Donanemab slowed clinical progression by 22.3% and 28.9% relative to placebo as assessed by integrated AD Rating Scale (iADRS) and Clinical ...

7. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13700

How donanemab data address the coverage with evidence ... TRAILBLAZER-ALZ registration trials demonstrated that donanemab significantly slowed cognitive and functional decline in amyloid-positive early ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04437511

NCT04437511 | A Study of Donanemab (LY3002813) in ... The reason for this study is to see how safe and effective the study drug donanemab is in participants with early Alzheimer's disease.