A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of Low Doses of Nilotinib (Tasigna®) on Safety, Biomarkers and Clinical Outcomes in Subjects With Mild to Moderate Alzheimer's Disease

Plain English Summary

Impact of Nilotinib on Safety, Biomarkers and Clinical Outcomes in Mild to Moderate Alzheimer's Disease is a Phase 2 clinical trial sponsored by Georgetown University studying Alzheimer's Disease. This study tested if a drug called Nilotinib is safe and effective for people with mild to moderate Alzheimer's disease. It was for individuals aged 50 and older diagnosed with mild to moderate Alzheimer's, confirmed by specific biomarker tests. Participants took either Nilotinib or a placebo (inactive pill) daily for a year, involving regular clinic visits and tests. Standard Alzheimer's treatments like cholinesterase inhibitors were allowed, but participants could not be in other experimental drug trials. The trial aims to enroll 37 participants.

Official Summary

The investigators hypothesize that Nilotinib will be safe in individuals with mild to moderate AD. Specifically, investigators hypothesize that low daily oral doses of Nilotinib will lead to CSF penetration, CNS Abl inhibition, and stabilization of CSF total Tau and p-Tau231/181 and Abeta42/40 levels. The investigators hypothesize that Nilotinib will decrease brain load of amyloid using amyloid positron emission tomography (PET). The investigators also predict that Nilotinib will reduce CSF markers of cell death, including neuron specific enolase (NSE) and S100B.

Who Can Participate

Here is what you need to know about eligibility for this trial. You could join if you were 50 or older, had confirmed mild to moderate Alzheimer's with specific biomarker levels, and could take pills. You could not join if you had other types of dementia, a history of significant stroke, epilepsy, major psychiatric disorders, or certain heart conditions. Participants needed a caregiver to accompany them to visits and ensure they took their study medication. Specific heart rhythm (QTc interval) and blood test results had to be within certain ranges. This trial is studying Alzheimer's Disease, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measured the safety of Nilotinib by tracking any side effects or abnormal lab results participants experienced over 12 months. The specific primary outcome measures are: Safety will be measured by number of participants experiencing the occurrence of adverse events and/or abnormal laboratory values (12 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial explored Nilotinib, a cancer drug, as a potential new treatment to slow the progression of Alzheimer's disease by targeting specific biological processes in the brain. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Alzheimer's Disease, where improved treatment options are needed.

Investor Insight

This trial signals interest in repurposing existing drugs for Alzheimer's, a large market with significant unmet needs, though approval probability depends on demonstrating clear efficacy and safety. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of Nilotinib, and how it might interact with your current medications. Participation involved taking study medication daily for a year, attending regular clinic visits for assessments, and undergoing tests like blood draws and possibly spinal taps. A caregiver or study partner was required to help manage medication and attend appointments. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 37 participants

Interventions

• DRUG: Placebo Capsule(s) Once a Day by Mouth — 1 capsule of Placebo once a day for 6 months followed by 2 capsules of Placebo for another 6 months
• DRUG: Nilotinib Capsule(s) Once a Day by Mouth — 1 capsule of Nilotinib 150 mg once a day for 6 months followed by 2 capsules of Nilotinib (150 mg each capsule = 300 mb total) for the subsequent 6 months

Primary Outcomes

• Safety will be measured by number of participants experiencing the occurrence of adverse events and/or abnormal laboratory values (12 months)

Secondary Outcomes

• Effects of Nilotinib treatment on measurement of Nilotinib in the CSF (12 months)

Full Eligibility Criteria

Inclusion Criteria:

1. Age ≥ 50
2. Fluent in English
3. Biomarker confirmed AD with CSF level of Abeta42 \<600ng/mL
4. Able to ingest oral medications
5. Diagnosis of mild to moderate AD according to dementia criteria outlined by McKhann et al.
6. Neuroimaging (MRI or CT) consistent with the diagnosis of AD within the past year
7. MMSE between 17 and 24 (inclusive) at screening
8. Modified Hachinski score ≤ 4
9. QTc interval 350-460ms, inclusive
10. Caregiver/study partner to accompany participant to all visits and have direct contact with the participant \> 2 days/week
11. Written informed consent
12. Capability and willingness to comply with all study criteria
13. Supervision available for study medication
14. Stable medical conditions for 3 months prior to screening visit
15. Stable medications for 4 weeks prior to screening visit
16. Able to complete baseline assessments
17. Minimum of 6 years of education, or work history sufficient to exclude mental retardation
18. Stable use of cholinesterase inhibitors and memantine (U.S. FDA-approved medications for patients with probable AD), vitamin E (up to 400 IU daily), estrogens, aspirin (81-300 mg daily), and cholesterol-lowering agents for 3 months prior to screening is allowed.
19. Clinical laboratory values within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigator

Exclusion Criteria:

1. Non-AD dementia, probable AD with Down syndrome, APP, PS-1, or PS-2 mutations (known familial AD), LBD and Fronto-temporal dementia (FTD)
2. History of clinically significant stroke
3. Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or DSM-IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
4. Sensory impairment that would preclude participation/cooperation with the protocol
5. Patients with hypokalemia, hypomagnesaemia, or long QTc syndrome.
6. Concomitant drugs known to prolong the QTc interval (\>461ms) and history of cardiovascular disease, including myocardial infarction or cardiac failure, angina, arrhythmia
7. Prescribed strong CYP3A4 inhibitors or a medical history of liver or pancreatic disease
8. Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine, metabolic, renal or other systemic disease or laboratory abnormality
9. Active neoplastic disease, history of cancer five years prior to screening, including breast cancer (history of treated basal or squamous skin cancer, or stable prostate cancer are not exclusionary)
10. Pregnancy or possible pregnancy
11. Contraindications to LP: prior lumbosacral spine surgery, severe degenerative joint disease or deformity of the spine, platelets \< 100,000, use of Coumadin/warfarin, or history of a bleeding disorder
12. Contraindication to MRI
13. Evidence of more than 4 micro hemorrhages and/or hemosiderosis by a recent (12 months) and/or the screening MRI.
14. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
15. Enrolled in another active trial investigating an experimental drug or therapy for AD
16. HIV positive

Trial Locations

• Georgetown University Medical Center, Washington D.C., District of Columbia, United States

Frequently Asked Questions

Related Conditions

• Alzheimer's Disease
• Dementia
• Neurodegenerative Diseases
• Mild Cognitive Impairment
• Parkinson's Disease
• Lewy Body Dementia
• Frontotemporal Dementia
• Vascular Dementia
• Amyotrophic Lateral Sclerosis (ALS)
• Huntington's Disease

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