Gantenerumab for Alzheimer's Disease

(DIAN-TU Trial)

Recruiting at 42 trial locations

Overseen By Ellen Ziegemeier

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressives, Anticoagulants

Disqualifiers: Neurologic disease, Psychiatric disease, Stroke, Alcohol use, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

280 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new drug, Gantenerumab, to determine if it can help individuals with a specific genetic mutation linked to Alzheimer's disease. The researchers will assess whether the drug can slow or prevent the buildup of harmful brain proteins, believed to contribute to Alzheimer's. Participants will receive either the drug or a placebo to compare effects. Suitable candidates have a known family mutation linked to Alzheimer's but have not yet shown cognitive symptoms. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking Alzheimer's research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on stable doses of any non-excluded medications for at least 30 days before the trial starts. Some medications, like immunosuppressive drugs, are not allowed within 90 days before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that remternetug has been tested for safety in people with early-stage Alzheimer's disease. In these studies, participants generally tolerated remternetug well. Some experienced mild side effects, but these were manageable. Importantly, no serious side effects directly linked to the drug were reported. This suggests that remternetug may be safe for humans, based on the available data from these trials. However, as with any treatment, all potential risks should be considered and discussed with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Gantenerumab is unique because it targets amyloid-beta plaques in the brain, which are believed to play a key role in the development of Alzheimer's disease. Unlike other treatments that primarily focus on managing symptoms, Gantenerumab aims to modify the disease process itself by reducing these plaques. Researchers are excited about this approach because, if successful, it could potentially slow or halt the progression of the disease rather than just alleviate symptoms. Additionally, the trial includes Remternetug, another promising treatment that is being tested in both blinded and open-label stages, offering further insights into its effectiveness and safety.

What evidence suggests that Gantenerumab might be an effective treatment for Alzheimer's?

Research has shown that remternetug, which participants in this trial may receive, may help reduce amyloid plaques—sticky clumps that build up in the brains of people with Alzheimer's. One study found that 75% of participants taking remternetug experienced significant plaque reduction within 169 days. This is important because amyloid plaques are thought to contribute to the symptoms and progression of Alzheimer's disease. However, gantenerumab, another treatment option in this trial, did not slow the disease's progression in previous studies involving more than 2,800 participants. Overall, while remternetug appears effective at clearing plaques, it remains uncertain if it can slow down Alzheimer's disease itself. ^{1 3 6 7 8}

Who Is on the Research Team?

Eric M McDade, DO

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a genetic mutation linked to early onset Alzheimer's Disease (AD), or those with a 50% chance of having the mutation. Participants must be within certain years of expected symptom onset, have normal cognitive function, and agree to use contraception if applicable. Those already on stable medication can join, except for certain episodic treatments.

Inclusion Criteria

Informed consent form (ICF) is signed and dated by the participant and study partner, or by the participant's legally acceptable representative (LAR) if applicable, according to local regulations for the ICF and, if applicable, the DIAN-TU cognitive run-in (CRI) ICF and/or country-specific ICFs.

Women of childbearing potential, if partner is not sterilized, must agree to use effective contraceptive measures (e.g., hormonal contraception, intra-uterine device, sexual abstinence, barrier method with spermicide) from Screening visit (V1) until 16 weeks after last dose of study drug.

Participant is a carrier of a mutation in an APP, PSEN1, or PSEN2 gene that is associated with DIAD or does not know their mutation status and has a 50% chance of having an AD-causing mutation (e.g., parent or biological sibling clinically affected with known AD-causing mutation in family).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1 Treatment

Blinded placebo-controlled period to test if the study drug can slow, prevent, or reverse progression of Aβ pathology

208 weeks

Regular visits for biomarker and cognitive assessments

Stage 2 Treatment

Open-label period to assess the study drug's effect on non-amyloid biomarkers of AD

208 weeks

Regular visits for biomarker and cognitive assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gantenerumab
• Matching Placebo (Gantenerumab)

Trial Overview

The study tests Gantenerumab against a placebo in preventing or slowing amyloid beta accumulation in the brain, as seen by PET imaging. It also examines whether reducing amyloid plaques early affects AD progression by comparing biomarkers with an external control group.

How Is the Trial Designed?

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

Gantenerumab is already approved in United States for the following indications:

Approved in United States as Gantenerumab for:

• Early onset Alzheimer's disease caused by a genetic mutation

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

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

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

Gantenerumab treatment led to a dose-dependent reduction in brain amyloid levels in patients with mild-to-moderate Alzheimer's disease, with a significant reduction of -35.7% observed in the 200 mg group compared to placebo.

The mechanism of action appears to involve phagocytosis of amyloid by human microglial cells, indicating that gantenerumab may help clear amyloid plaques from the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Ostrowitzki, S., Deptula, D., Thurfjell, L., et al.[2019]

Gantenerumab, an anti-amyloid-β monoclonal antibody, was well tolerated in a study of 50 healthy volunteers, with no serious adverse events reported and only mild, transient injection site reactions observed.

Both 5-second and 15-second subcutaneous injection speeds resulted in comparable pain levels and pharmacokinetic profiles, suggesting that gantenerumab could be administered at home by patients with Alzheimer's disease or their caregivers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study to Assess the Effect of Speed of Injection on Pain, Tolerability, and Pharmacokinetics After High-volume Subcutaneous Administration of Gantenerumab in Healthy Volunteers. Portron, A., Jordan, P., Draper, K., et al.[2020]

In a study of 1332 patients with Alzheimer's disease or other dementias in France, the prevalence of adverse drug reactions (ADRs) was found to be 5.0%, with serious ADRs occurring in 31.9% of cases, highlighting the potential risks associated with medication in this population.

The most common ADRs were gastrointestinal, central nervous system, and psychiatric disorders, with anti-dementia and psychotropic drugs being the most frequently implicated, indicating a need for careful monitoring and prescribing practices in patients with dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions in patients with Alzheimer's disease and related dementia in France: a national multicentre cross-sectional study. Laroche, ML., Perault-Pochat, MC., Ingrand, I., et al.[2013]

In a phase III trial involving 797 patients with prodromal Alzheimer's disease, gantenerumab did not show significant efficacy compared to placebo, leading to the study being halted early for futility after 2 years.

While no overall clinical benefits were observed, exploratory analyses indicated that higher doses of gantenerumab might be necessary to achieve potential efficacy, and there was an increased incidence of amyloid-related imaging abnormalities associated with higher doses and certain genetic factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease. Ostrowitzki, S., Lasser, RA., Dorflinger, E., et al.[2019]

Gantenerumab, an anti-amyloid monoclonal antibody, is being developed to treat early Alzheimer's disease and aims to reverse amyloid plaque buildup, potentially slowing disease progression.

The development of gantenerumab has incorporated over 20 years of research, focusing on confirmed amyloid positivity and using blood-based biomarkers to optimize dosing and ensure a more effective treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gantenerumab: an anti-amyloid monoclonal antibody with potential disease-modifying effects in early Alzheimer's disease. Bateman, RJ., Cummings, J., Schobel, S., et al.[2022]

Gantenerumab is an investigational monoclonal antibody that targets and removes beta-amyloid plaques in the brain, which are associated with Alzheimer's disease, and shows promise as a disease-modifying treatment rather than just a symptomatic one.

Current Alzheimer's medications primarily provide temporary symptom relief, but gantenerumab is currently in Phase II and III clinical trials, indicating its potential to alter the disease's progression, which is a significant advancement in Alzheimer's treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of gantenerumab and its potential in the treatment of Alzheimer's disease. Novakovic, D., Feligioni, M., Scaccianoce, S., et al.[2021]

Citations

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nejm.org

nejm.org/doi/full/10.1056/NEJMoa2304430

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Amyloid clearance was achieved by 75% of participants who received remternetug at doses ranging from 700 to 2800 mg IV Q4Q by day 169.

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