Anti-Inflammatory Drugs for Mild Alzheimer's Disease

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

34 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing anti-inflammatory drugs to see if they can help people with early Alzheimer's disease who have signs of inflammation. The goal is to see if reducing inflammation can improve memory and thinking. The study will also check if these drugs are safe and well-tolerated. The trial aims to determine if these drugs can prevent Alzheimer's disease.

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.

What data supports the effectiveness of the drug Canakinumab for treating mild Alzheimer's disease?

Canakinumab has been effective in reducing inflammation in various inflammatory diseases, such as CAPS and adult-onset Still's disease, by targeting IL-1β, a protein involved in inflammation. While it hasn't been specifically tested for Alzheimer's, its ability to control inflammation might be beneficial, as inflammation is a component of Alzheimer's disease. ^{1 2 3 4 5}

How does the drug Canakinumab differ from other treatments for Alzheimer's disease?

Canakinumab is unique because it is an anti-inflammatory drug that targets a specific part of the immune system, potentially reducing inflammation in the brain, which is a different approach compared to other Alzheimer's treatments that focus on clearing amyloid plaques. ^{6 7 8 9 10}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. Spain pubmed.ncbi.nlm.nih.gov

[Canakinumab, a monoclonal antibody against IL-1β, with potential utility in different inflammatory processes]. [2019]

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

Down-regulated Th17 cells in a patient with familial Mediterranean fever associated with amyloid A amyloidosis in the treatment of canakinumab. [2023]

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

Bioequivalence of Canakinumab Injected Subcutaneously via an Autoinjector Device or a Prefilled Safety Syringe Device in Healthy Subjects. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic properties of canakinumab, a human anti-interleukin-1β monoclonal antibody. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Distinct Effects of Interleukin-1β Inhibition upon Cytokine Profile in Patients with Adult-Onset Still's Disease and Active Articular Manifestation Responding to Canakinumab. [2021]

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

ABBY: A phase 2 randomized trial of crenezumab in mild to moderate Alzheimer disease. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Comparing the efficacy and neuroinflammatory potential of three anti-abeta antibodies. [2018]

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

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer's Disease. [2022]

9. England pubmed.ncbi.nlm.nih.gov

NM101 Phase III study of NE3107 in Alzheimer's disease: rationale, design and therapeutic modulation of neuroinflammation and insulin resistance. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Investigating Partially Discordant Results in Phase 3 Studies of Aducanumab. [2023]