Remternetug for Alzheimer's Disease

(DIAN-TU-002 Trial)

Recruiting at 34 trial locations

Overseen By Sarah Berman

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Washington University School of Medicine

Must not be taking: Anticoagulants, Immunosuppressives, Chemotherapeutics, others

Disqualifiers: Neurologic, Psychiatric, Stroke, Substance use, others

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

Compensation: Varies

Number of Visits: Unknown

280 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to test the study drug, referred to as remternetug, to determine its effectiveness for the study treatment of asymptomatic (at risk) Alzheimer disease in individuals with AD-causing mutations. This study will also investigate the effects of remternetug on biomarkers (measures of the disease including brain scans, blood and spinal fluid tests), examine safety data to identify any potential benefits or risks, and examine how well participants can tolerate remternetug. Stage 1 will determine if treatment with the study drug prevents or reverses amyloid beta (Aβ) accumulation compared with placebo in participants with dominantly inherited Alzheimer's disease (DIAD). Stage 2 will evaluate the effect of early anti-amyloid treatment on downstream biomarkers of AD in treated participants compared to external control groups.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, it mentions that participants should be on stable doses of their current medications for at least 30 days before starting the trial, except for medications taken for episodic conditions. Approved treatments for Alzheimer's and other medications may be permitted.

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

Remternetug is unique because it is a new investigational drug specifically being studied for Alzheimer's disease, whereas current standard treatments like cholinesterase inhibitors and memantine focus on different mechanisms, such as enhancing neurotransmitter activity or blocking certain brain receptors. ^{1 2 3 4 5}

Research Team

Eric M McDade, DO

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for individuals who have a genetic form of Alzheimer's disease but do not yet show symptoms. They must carry mutations that cause the disease and are at risk of developing it. Specific details about inclusion or exclusion criteria were not provided.

Inclusion Criteria

I agree not to try to become pregnant during and shortly after the study.

I have been on stable medication for over 30 days for a condition that is not excluded from the study.

Provide written informed consent, signed, and dated by the participant and study partner, or by the participant's legally authorized representative if applicable, according to local regulations for the ICF and, if applicable, country specific ICFs

Exclusion Criteria

I am able to complete all required initial visit tests and assessments.

My brain MRI does not show significant issues like major bleeding, brain damage, or aneurysms.

Any other medical condition that could be expected to progress, recur, or change to such an extent that it could bias the assessment of the clinical or mental status of the participant to a significant degree or put the participant at special risk

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1 Treatment

Participants receive remternetug or placebo to assess prevention or reversal of amyloid beta accumulation

104 weeks

Regular visits for imaging and biomarker assessments

Stage 2 Treatment

Evaluation of early anti-amyloid treatment effects on downstream biomarkers compared to control groups

192 weeks

Visits at Weeks 0, 48, 96, 144, and 192 for biomarker and cognitive assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Treatment Details

Interventions

• Matching Placebo (Remternetug)
• Remternetug

Trial Overview The study tests remternetug, which might prevent or slow down Alzheimer's in people with inherited risk. It compares remternetug to a placebo (inactive substance) using brain scans and other tests to measure its effect on the disease's biomarkers.

Participant Groups

Group I: Stage 1: Remternetug Experimental Treatment 1 Intervention

Active Remternetug- blinded

Group II: Stage 2: Remternetug Open Label Active Control 1 Intervention

Open label will start after last dose of Stage 1

Group III: Stage 1: Matching placebo (Remternetug) Placebo Group 1 Intervention

Matching placebo

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Eli Lilly and Company

Industry 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

GHR Foundation

Collaborator

Trials

1

Recruited

280+

Private Donors

Collaborator

Trials

1

Recruited

280+

Findings from Research

In a study involving 30 patients aged 55 to 84 with moderate to severe Alzheimer's disease, memantal (a generic form of memantine) demonstrated moderate positive effects on cognitive functions and daily activities over a 3-month treatment period.

The treatment was found to be safe, with no adverse effects reported, indicating that memantal is both effective and well-tolerated for managing symptoms of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical experience of the use of memantal in patients with moderate and severe Alzheimer's disease]. Gavrilova, SI., Kolykhalov, IV., Kulik, AS., et al.[2018]

Cholinesterase inhibitors are currently the only approved medications for treating cognitive deficits in Alzheimer's disease, showing efficacy in clinical trials by compensating for the loss of acetylcholine.

Antioxidant drugs like alpha-tocopherol (vitamin E) and selegiline have shown marginal benefits over placebo in slowing functional decline in patients with moderately advanced Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic approaches to cognitive deficits in Alzheimer's disease. Peskind, ER.[2018]

In a study involving 403 patients with mild to moderate Alzheimer's disease, memantine (20 mg/day) showed significant improvements in cognitive function and global status compared to placebo over 24 weeks.

The treatment was generally safe, with a slightly higher rate of discontinuations due to adverse events in the memantine group (9.5%) compared to placebo (5.0%), indicating that while memantine is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial. Peskind, ER., Potkin, SG., Pomara, N., et al.[2022]

A six-month study involving 50 patients with mild to moderate Alzheimer's disease found that both original memantine and the generic version (memantal) showed similar efficacy in improving cognitive functions and neuropsychiatric symptoms.

There were no significant differences in safety or effectiveness between the two medications, indicating that the generic memantal is a viable alternative to the original memantine for treating dementia in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A comparison of the efficacy and safety of memantal and original memantine in the treatment of mild and moderate dementia in Alzheimer's disease]. Shiryaev, OY., Shapovalov, DL., Polozova, TM., et al.[2018]

In a 24-week study involving 470 patients with mild to moderate Alzheimer's disease, memantine (20 mg/day) demonstrated significant improvements in cognitive function compared to placebo, particularly at weeks 12 and 18.

Memantine was well tolerated, with side effects similar to those experienced by patients on placebo, indicating a favorable safety profile for its use in treating Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study. Bakchine, S., Loft, H.[2022]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Clinical experience of the use of memantal in patients with moderate and severe Alzheimer's disease]. [2018]

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

Pharmacologic approaches to cognitive deficits in Alzheimer's disease. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial. [2022]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[A comparison of the efficacy and safety of memantal and original memantine in the treatment of mild and moderate dementia in Alzheimer's disease]. [2018]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study. [2022]