Donanemab for Early Alzheimer's Disease

Not currently recruiting at 66 trial locations

Overseen By Mark Goldstein, MD

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different doses of donanemab, a treatment for early Alzheimer's disease, to assess its impact on a potential side effect known as ARIA-E (a type of brain swelling). Researchers aim to determine which doses are most effective and which participant characteristics might predict the risk of ARIA-E. Participants will receive donanemab through an IV infusion and may also receive a placebo or other pretreatments to maintain study objectivity. Individuals who have noticed memory changes for at least six months and have a specific brain scan result showing amyloid (protein) build-up are suitable candidates for this trial. As a Phase 3 trial, this study 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 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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that donanemab, an antibody treatment, is being tested for safety and effectiveness in people with early Alzheimer's disease. Previous studies found that donanemab targets and reduces amyloid plaques in the brain, which are believed to contribute to Alzheimer's.

In terms of safety, donanemab has generally been well-tolerated in studies. Some participants experienced side effects like ARIA-E, a type of brain swelling, but these cases were mostly mild or moderate. The FDA has already approved the treatment for early Alzheimer's, indicating a known safety profile based on clinical trial data. However, discussing potential risks with a doctor before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about donanemab for early Alzheimer's disease because it targets amyloid plaques in the brain, which are believed to play a key role in the progression of the disease. This is different from traditional treatments like cholinesterase inhibitors or NMDA receptor antagonists, which focus on managing symptoms rather than altering disease progression. Donanemab, administered via IV infusion, has the potential to slow cognitive decline by directly interfering with the underlying pathology of Alzheimer's, offering hope for more effective long-term management of the condition.

What evidence suggests that this trial's treatments could be effective for early Alzheimer's disease?

Research has shown that donanemab, a treatment for early Alzheimer's disease, yields promising results. In earlier studies, participants who took donanemab experienced slower disease progression over 76 weeks compared to those on a placebo (a harmless pill with no active drug). Notably, 52% of patients with low to medium levels of tau, a protein linked to Alzheimer's, showed significant improvement within a year. Donanemab targets and reduces amyloid-beta plaques, which are thought to contribute to Alzheimer's symptoms. These findings suggest that donanemab may effectively slow the progression of early Alzheimer's disease. Participants in this trial will receive different dose levels of donanemab or additional pretreatments to further evaluate its effectiveness. ^{1 4 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 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

A mini mental state examination (MMSE) score of 20 to 28 (inclusive) at screening

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

Have an amyloid PET scan result from central read, consistent with the presence of amyloid pathology

Exclusion Criteria

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

Contraindication to MRI or PET scans

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: 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 II: 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.

Group III: 1400 mg Donanemab - Titration Experimental Treatment 2 Interventions

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.

Group IV: 1400 mg Donanemab - Standard Regimen Experimental Treatment 2 Interventions

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.

Group V: 1400 mg Donanemab - Maximum Concentration (Cmax) Experimental Treatment 2 Interventions

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.

Group VI: 1400 mg Donanemab - Dose Skipping Experimental Treatment 2 Interventions

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.

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

Donanemab in Early Alzheimer's Disease Efficacy Outcomes. The primary outcome was the change from baseline to 76 weeks in the score on the Integrated Alzheimer's Disease Rating ...

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

Donanemab in Early Symptomatic Alzheimer Disease - PubMed Main outcomes and measures: The primary outcome was change in integrated Alzheimer Disease Rating Scale (iADRS) score from baseline to 76 ...

4. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70491

Donanemab exposure‐response in early symptomatic ... In the TRAILBLAZER-ALZ study, donanemab-treated participants showed less disease progression at 76 weeks compared to placebo-treated ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9818878/

Donanemab for Alzheimer's Disease: A Systematic Review of ... This systematic review critically reviews the latest evidence of Donanemab, a humanized antibody that targets the reduction in Aβ plaques, in AD patients.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33720637/

Donanemab in Early Alzheimer's Disease Donanemab, an antibody that targets a modified form of deposited Aβ, is being investigated for the treatment of early Alzheimer's disease.

7. pro.alz.org pro.alz.org/hub/care-pathway/treatment/donanemab-toolkit

Donanemab Resources for Health Care Professionals - ALZPro Donanemab received FDA approval based on clinical trial evidence demonstrating its ability to target amyloid plaques and slow cognitive progression in early AD.

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.