Gantenerumab for Alzheimer's Disease

(DIAN-TU Trial)

Recruiting in Palo Alto (17 mi)

+35 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressives, Anticoagulants

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

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

The purpose is to evaluate the biomarker effect, safety, and tolerability of investigational study drugs in participants who are known to have an Alzheimer's disease (AD)-causing mutation. Stage 1 will determine if treatment with the study drug prevents or slows the rate of amyloid beta (Aβ) pathological disease accumulation demonstrated by Aβ positron emission tomography (PET) imaging. Stage 2 will evaluate the effect of early Aβ plaque reduction/prevention on disease progression by assessing downstream non-Aβ biomarkers of AD (e.g., CSF total tau, p-tau, NfL) compared to an external control group from the DIAN-OBS natural history study and the DIAN-TU-001 placebo-treated participants.

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.

What evidence supports the effectiveness of the drug gantenerumab for Alzheimer's disease?

Gantenerumab is a drug that targets and removes amyloid plaques in the brain, which are associated with Alzheimer's disease. Research suggests it has the potential to modify the disease by slowing or stopping its progression, similar to other anti-amyloid drugs like aducanumab, which has been approved for Alzheimer's treatment. ^{1 2 3 4 5}

Is gantenerumab safe for humans?

Gantenerumab has been tested in clinical trials for Alzheimer's disease, and studies have looked at its safety, including how it is tolerated when injected under the skin. While the research focuses on Alzheimer's, it provides some information on safety in humans, such as the pain and tolerability of injections. ^{1 3 4 5 6}

Research Team

Eric M McDade, DO

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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.

Participant is at least 18 years old.

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.

Trial Timeline

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

Treatment Details

Interventions

• Gantenerumab (Monoclonal Antibodies)
• Matching Placebo (Gantenerumab) (Other)

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.

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+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

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+

Dr. Joanne Pike

Alzheimer's Association

Chief Executive Officer since 2023

DrPH in Public Health Leadership from the University of North Carolina at Chapel Hill

Dr. Maria C. Carrillo

Alzheimer's Association

Chief Medical Officer

PhD in Neuroscience

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Dr. Richard J. Hodes

National Institute on Aging (NIA)

Chief Executive Officer since 1993

MD from Harvard Medical School

Dr. Marie Bernard

National Institute on Aging (NIA)

Chief Medical Officer

MD from Harvard Medical School

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

Findings from Research

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]

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 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]

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, 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]

References

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

Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. [2019]

2. England pubmed.ncbi.nlm.nih.gov

A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of gantenerumab and its potential in the treatment of Alzheimer's disease. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Gantenerumab: an anti-amyloid monoclonal antibody with potential disease-modifying effects in early Alzheimer's disease. [2022]

5. United States 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. [2020]

6. England 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. [2013]