Gantenerumab for Alzheimer's Disease (DIAN-TU Trial)
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Washington University School of Medicine
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.
Is the drug Gantenerumab a promising treatment for Alzheimer's Disease?The information provided does not include any details about Gantenerumab or its effectiveness in treating Alzheimer's Disease. Therefore, we cannot determine if it is a promising treatment based on the given data.12358
What safety data is available for Gantenerumab in treating Alzheimer's?Gantenerumab is a fully human anti-amyloid beta monoclonal antibody being developed for Alzheimer's disease. It has undergone Phase I, II, and III clinical trials. Safety data from these trials indicate that gantenerumab has been evaluated for pain, tolerability, and pharmacokinetics, particularly in subcutaneous administration. The trials have incorporated learnings from previous research, including confirmed amyloid positivity and exposure-response models to ensure safe dosing. However, like other anti-amyloid treatments, there have been challenges with treatment-limiting adverse events. The development program has focused on minimizing these risks while aiming for disease-modifying effects.4671011
What data supports the idea that Gantenerumab for Alzheimer's Disease is an effective treatment?The available research shows that Gantenerumab is being studied as a potential treatment for Alzheimer's Disease. It is designed to remove harmful plaques in the brain that are associated with the disease. Some studies suggest it might slow down the progression of Alzheimer's, which is different from current treatments that only ease symptoms temporarily. However, the research is still ongoing, and it is not yet clear how effective Gantenerumab is compared to other treatments like cholinesterase inhibitors.4791011
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you must stop taking your current medications. However, you must be on stable doses of any non-excluded medications for at least 30 days before the baseline visit. Some medications, like immunosuppressive drugs, must be stopped 90 days prior, and certain anticoagulants are not allowed. It's best to discuss your specific medications with the trial team.
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.Treatment Details
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.
3Treatment groups
Experimental Treatment
Active Control
Placebo Group
Group I: Stage 1: RemternetugExperimental Treatment1 Intervention
Active Remternetug- blinded
Group II: Stage 2: Remternetug Open LabelActive Control1 Intervention
Open label will start after last dose of Stage 1
Group III: Stage 1: Matching Placebo (Remternetug)Placebo Group1 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
USC Keck School of MedicineLos Angeles, CA
Washington University in St. LouisSaint Louis, MO
University of Alabama in BirminghamBirmingham, AL
University of California San Diego Medical CenterLa Jolla, CA
More Trial Locations
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Who is running the clinical trial?
Washington University School of MedicineLead Sponsor
Eli Lilly and CompanyIndustry Sponsor
Hoffmann-La RocheIndustry Sponsor
Alzheimer's AssociationCollaborator
National Institute on Aging (NIA)Collaborator
Genentech, Inc.Industry Sponsor
References
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Infliximab retreatment in adults and children with Crohn's disease: risk factors for the development of delayed severe systemic reaction. [2015]Although effective in the treatment of refractory Crohn's disease, episodic retreatment with the antitumor necrosis factor a chimeric monoclonal antibody infliximab (Remicade, Centocor, Malvern, PA) can be associated with severe acute and delayed systemic reactions.
Certolizumab pegol in Crohn's disease. [2018]Certolizumab pegol is a humanized Fab' fragment monoclonal antibody to tumor necrosis factor alpha (TNF-alpha). PEGylation increases its half-life, and it is administered subcutaneously to treat immune-mediated inflammatory diseases such as Crohn's disease and rheumatoid arthritis. Certolizumab pegol improves quality of life and reduces clinical disease activity. Inflammatory markers such as C-reactive protein (CRP) also decrease after administration of certolizumab pegol. The dose for induction of remission is 400 mg subcutaneously at weeks 0, 2 and 4. The dose for maintenance of remission is 400 mg sc given every four weeks. The safety profile is comparable with other anti-TNF agents, and the major adverse events are related to infections. This article reviews the published data regarding the efficacy and safety of certolizumab pegol.
Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. [2019]Gantenerumab is a fully human anti-Aβ monoclonal antibody in clinical development for the treatment of Alzheimer disease (AD).
Economical aspect of biological therapy in inflammatory conditions in Hungary. [2013]There has been a burst in the use of biological therapies in the past decade resulting in increasing costs. In 2006 - 2010 the following biological agents were available in Hungary: adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, tocilizumab, and ustekinumab. All biological agents except rituximab were first line therapies; rituximab was a second line option in rheumatoid arthritis.
Adverse drug reactions in patients with Alzheimer's disease and related dementia in France: a national multicentre cross-sectional study. [2013]To assess the prevalence of adverse drug reactions (ADRs) occurring in patients with Alzheimer's disease (AD) or other dementia in France.
Profile of gantenerumab and its potential in the treatment of Alzheimer's disease. [2021]Alzheimer's disease, which is characterized by gradual cognitive decline associated with deterioration of daily living activities and behavioral disturbances throughout the course of the disease, is estimated to affect 27 million people around the world. It is expected that the illness will affect about 63 million people by 2030, and 114 million by 2050, worldwide. Current Alzheimer's disease medications may ease symptoms for a time but are not capable of slowing down disease progression. Indeed, all currently available therapies, such as cholinesterase inhibitors (donepezil, galantamine, rivastigmine), are primarily considered symptomatic therapies, although recent data also suggest possible disease-modifying effects. Gantenerumab is an investigational fully human anti-amyloid beta monoclonal antibody with a high capacity to bind and remove beta-amyloid plaques in the brain. This compound, currently undergoing Phase II and III clinical trials represents a promising agent with a disease-modifying potential in Alzheimer's disease. Here, we present an overview of gantenerumab ranging from preclinical studies to human clinical trials.
Two year follow-up of Crohn's patients substituted to certolizumab anti-TNFa therapy: SAVANT 2. [2020]The effectiveness of ant-TNF 'biologic' therapy in is well supported in the management of moderate to severe Crohn's Disease (CD). Our first 'SAVANT' study was to our knowledge the first study report one- year outcomes in patients (n=60) who switched from previous anti-TNFa treatment to Cimzia/Certolizumab. This current study (SAVANT 2) follows up on longer term outcomes and provides additional clinical and biochemical data that may contribute to therapeutic responses. This IRB approved study was a retrospective analysis of the initial patients included in SAVANT 1. Patients who were switched to TNF antagonist Certolizumab as an alternative biologic were followed an additional year. Retrospective consideration of immunomodulator use, smoking status and clinical data were also evaluated. Of 60 patients with moderate-severe CD who participated in the SAVANT 1 study, 15 patients were excluded due to inadequate follow up. 45 patients were studied for a total of two years following substitution with Certolizumab from prior anti TNF agent therapy. Clinical remission at 1 year was 75% (45/60) and 55% (25/45) at the second year. At the second year, 5 more patients had discontinued Certolizumab due to worse disease or adverse events, indicating a cumulative two-year failure rate of 33% (20/60). Smoking and concomitant use of immunomodulators were similar between 'success' and 'failure' groups. SAVANT 2, the first study to report long term outcomes of switching from Infliximab or Adalimumab to Certolizumab showed that at 2 years, 25 patient's maintained clinical remission. The discontinuation rates were 25 and 11% at years 1 & 2 respectively. The 5 patients who lost responsiveness after the first year were women, the majority of smoked. Additional prospective studies to assess the appropriateness and feasibility of biologic substitution are still needed.
A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease. [2019]Gantenerumab is a fully human monoclonal antibody that binds aggregated amyloid-β (Aβ) and removes Aβ plaques by Fc receptor-mediated phagocytosis. In the SCarlet RoAD trial, we assessed the efficacy and safety of gantenerumab in prodromal Alzheimer's disease (AD).
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]Gantenerumab, a fully human anti-amyloid-β IgG1 monoclonal antibody that binds to aggregated forms of amyloid-β, is being investigated as a potential disease-modifying treatment for early (prodromal to mild) Alzheimer disease (AD). Our study compared the pain associated with 5- and 15-s subcutaneous injections of gantenerumab and evaluated the tolerability and pharmacokinetic properties of subcutaneous gantenerumab.
Gantenerumab: an anti-amyloid monoclonal antibody with potential disease-modifying effects in early Alzheimer's disease. [2022]This review describes the research and development process of gantenerumab, a fully human anti-amyloid monoclonal antibody in development to treat early symptomatic and asymptomatic Alzheimer's disease (AD). Anti-amyloid monoclonal antibodies can substantially reverse amyloid plaque pathology and may modify the course of the disease by slowing or stopping its clinical progression. Several molecules targeting amyloid have failed in clinical development due to drug-related factors (e.g., treatment-limiting adverse events, low potency, poor brain penetration), study design/methodological issues (e.g., disease stage, lack of AD pathology confirmation), and other factors. The US Food and Drug Administration's approval of aducanumab, an anti-amyloid monoclonal antibody as the first potential disease-modifying therapy for AD, signaled the value of more than 20 years of drug development, adding to the available therapies the first nominal success since cholinesterase inhibitors and memantine were approved. BODY: Here, we review over 2 decades of gantenerumab development in the context of scientific discoveries in the broader AD field. Key learnings from the field were incorporated into the gantenerumab phase 3 program, including confirmed amyloid positivity as an entry criterion, an enriched clinical trial population to ensure measurable clinical decline, data-driven exposure-response models to inform a safe and efficacious dosing regimen, and the use of several blood-based biomarkers. Subcutaneous formulation for more pragmatic implementation was prioritized as a key feature from the beginning of the gantenerumab development program.