Anti-Inflammatory Drugs for Mild Alzheimer's Disease

No longer recruiting at 15 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must not be taking: Anti-inflammatories, Tau ASOs

Disqualifiers: Non-Alzheimer dementia, Parkinson's, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 10

Duration: 20 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether canakinumab, an anti-inflammatory medication, can improve thinking and memory in people with early Alzheimer's disease. It also examines the treatment's safety and its effect on body inflammation. Participants will receive either canakinumab or a placebo (a non-active treatment) through injections. Ideal candidates are those diagnosed with mild cognitive impairment or mild Alzheimer's disease and have a caregiver who can attend all appointments with them. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use any investigational or approved products intended to affect inflammation or Alzheimer's disease. If you have used such products before, they must be stopped for a certain period before joining the trial.

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

Research has shown that Canakinumab has undergone safety testing in people with various health conditions. In earlier studies, common side effects included injection site reactions, infections, and stomach pain. These side effects appeared when Canakinumab was used for other purposes. It's important to note that these are possible side effects and may not occur in everyone.

The extensive testing of Canakinumab in many studies suggests it is generally well-tolerated. However, since this trial focuses on Alzheimer's, individual experiences can vary. Prospective participants should discuss any health concerns with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Most treatments for mild Alzheimer's disease focus on managing symptoms with medications like cholinesterase inhibitors and NMDA receptor antagonists. However, Canakinumab is unique because it targets inflammation, which is believed to play a role in Alzheimer's progression. This drug is an anti-inflammatory monoclonal antibody that specifically inhibits interleukin-1β, a pro-inflammatory cytokine. Researchers are excited about Canakinumab because it offers a novel approach by potentially slowing down the disease process itself, rather than just addressing symptoms.

What evidence suggests that Canakinumab could be an effective treatment for mild Alzheimer's disease?

Research shows that Canakinumab, which participants in this trial may receive, may help reduce inflammation, believed to contribute to Alzheimer's disease. In past studies, Canakinumab successfully reduced inflammation in other conditions, suggesting it might also help with Alzheimer's by addressing the same issue. While researchers are still collecting direct evidence of its effects on Alzheimer's symptoms, the reduction of inflammation is a hopeful sign. By lowering inflammation, Canakinumab could potentially slow memory and thinking problems in people with mild Alzheimer's. This approach is based on the belief that inflammation might worsen disease symptoms. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for men and women aged 45-90 with mild cognitive impairment or mild Alzheimer's, confirmed by specific criteria including amyloid and tau presence. Participants must have a caregiver and meet certain cognitive test score requirements. Those with other neurological conditions, major cerebrovascular disease, or using inflammation-modulating treatments are excluded.

Inclusion Criteria

I am between 45 and 90 years old.

Your MMSE score is between 20 and 24.

Participant has a reliable study partner or caregiver can accompany the participant to all visits

Exclusion Criteria

I do not have any brain or mental health conditions that could affect my thinking or memory.

I have been diagnosed with vascular dementia.

I am using a treatment aimed at changing the course of Alzheimer's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

7-8 weeks

1 visit (in-person)

Baseline

Participants undergo baseline assessments before starting treatment

1 week

1 visit (in-person)

Treatment

Participants receive Canakinumab or placebo for 20 weeks

20 weeks

6 visits (in-person, every 4 weeks)

Study Completion Evaluation

Evaluation approximately 30 days after the last agent administration

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

20 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Canakinumab
• Placebo

Trial Overview The study tests the effectiveness of Canakinumab, an anti-inflammatory agent, against a placebo in improving cognition for early Alzheimer's patients. It also assesses safety and effects on both brain and body inflammation.

How Is the Trial Designed?

Group I: Canakinumab Experimental Treatment 1 Intervention

Canakinumab 150 mg SC once every 4 weeks for the first 2 doses followed by 300 mg SC once every 4 weeks for the subsequent 4 doses.

Group II: Placebo Placebo Group 1 Intervention

Matching placebo sub-cutaneous injections

Canakinumab is already approved in European Union, United States for the following indications:

Approved in European Union as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Approved in United States as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a phase 2 trial involving 431 patients with mild to moderate Alzheimer's disease, crenezumab did not meet the primary efficacy endpoints for improving cognitive function over 68 weeks, indicating it may not significantly enhance cognition or function overall.

However, an exploratory analysis suggested that high-dose crenezumab may reduce cognitive decline in patients with milder forms of Alzheimer's, particularly those with Mini-Mental State Examination scores of 22 to 26, warranting further investigation into higher doses for early-stage patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ABBY: A phase 2 randomized trial of crenezumab in mild to moderate Alzheimer disease. Cummings, JL., Cohen, S., van Dyck, CH., et al.[2022]

Aducanumab, the first FDA-approved therapy for Alzheimer's disease, has been shown to reduce clinical decline in patients with mild cognitive impairment and mild dementia, based on data from the phase 3 EMERGE trial.

Long-term modeling predicts that aducanumab treatment can lead to significant benefits, including an increase of 0.65 quality-adjusted life-years (QALYs) per patient and a delay in the progression to more severe stages of Alzheimer's, providing both clinical and socioeconomic advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer's Disease. Herring, WL., Gould, IG., Fillit, H., et al.[2022]

In the phase 3 studies EMERGE and ENGAGE, high-dose aducanumab showed significant treatment effects in EMERGE but not in ENGAGE, with post-hoc analyses revealing that differences were influenced by a small number of rapidly progressing patients and lower exposure to the target dose in ENGAGE.

The results were consistent in later enrolled patients who received the target dose of 10 mg/kg, indicating that proper dosing and patient selection are crucial for the efficacy of aducanumab in treating early Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating Partially Discordant Results in Phase 3 Studies of Aducanumab. Mallinckrodt, C., Tian, Y., Aisen, PS., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04795466

NCT04795466 | Study of the Efficacy and Safety of Various ... The purpose of this platform study was to evaluate the effect of anti-inflammatory agents on cognition in early Alzheimer's disease.

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/66/NCT04795466/SAP_001.pdf

Clinical Development agents in patients with mild cognitive impairment due to. Alzheimer's disease and mild Alzheimer's disease. Statistical Analysis Plan (SAP).

3. withpower.com withpower.com/trial/phase-3-alzheimer-disease-7-2021-3bc9c

Anti-Inflammatory Drugs for Mild Alzheimer's Disease What data supports the effectiveness of the drug Canakinumab for treating mild Alzheimer's disease? Canakinumab has been effective in reducing inflammation ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11040692/

Alzheimer's disease drug development pipeline: 2024 - PMC The goal of our annual review of the AD drug development pipeline is to note trends in the therapeutic targets, use of clinical outcome measures ...

5. ctv.veeva.com ctv.veeva.com/study/study-of-the-efficacy-and-safety-of-various-anti-inflammatory-agents-in-participants-with-mild-cogni

Study of the Efficacy and Safety of Various Anti-inflammatory ... The purpose of this platform study was to evaluate the effect of anti-inflammatory agents on cognition in early Alzheimer's disease.

6. sciencedirect.com sciencedirect.com/topics/neuroscience/canakinumab

Canakinumab - an overview | ScienceDirect Topics Safety and Tolerability. Injection site reactions, infections, and abdominal pain were the most common adverse events observed in the Phase III clinical trials ...