Impact of Nilotinib on Safety, Biomarkers and Clinical Outcomes in Mild to Moderate Alzheimer's Disease

NCT02947893 | Completed Phase 2 DMC

• 1 other identifier: 2016-0315
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer's Disease

Keywords

Nilotinib in Alzheimer's disease

Outcome Measures

Primary Outcomes (1)

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

  Safety will be measured by assessing number of participants with abnormal laboratory values, as well as adverse events (AEs) and serious adverse events (SAEs) deemed to be possibly, probably, or definitely related to the study drug.

  12 months

Secondary Outcomes (1)

• Effects of Nilotinib treatment on measurement of Nilotinib in the CSF

  12 months

Study Arms (2)

Group 1 (placebo)

PLACEBO COMPARATOR

Out of 42 total participants with mild to moderate AD (MMSE=17-24 inclusive) and their study partners that will be recruited and 1:1 randomized, 21 (twenty-one) will be assigned to group 1 and given 1 capsule of a placebo drug by mouth every day for the first 6 months followed by 2 capsules once daily for the subsequent 6 months, every time taken without a meal, for the total duration of the study for 12 months.

Drug: Placebo Capsule(s) Once a Day by Mouth

Group 2 (treated)

ACTIVE COMPARATOR

Out of 42 total participants with mild to moderate AD (MMSE=17-24 inclusive) and their study partners that will be recruited and 1:1 randomized, 21 (twenty-one) will be assigned to group 2 treated with 1 capsule (150mg Nilotinib) once a day by mouth for the first 6 months followed by dose escalation to 2 capsules (300mg Nilotinib) once daily by mouth for the subsequent 6 months, every time taken without a meal, for the total study duration of 12 months.

Drug: Nilotinib Capsule(s) Once a Day by Mouth

Interventions

Placebo Capsule(s) Once a Day by Mouth DRUG

1 capsule of Placebo once a day for 6 months followed by 2 capsules of Placebo for another 6 months

Group 1 (placebo)

Nilotinib Capsule(s) Once a Day by Mouth DRUG

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

Group 2 (treated)

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 50
• Fluent in English
• Biomarker confirmed AD with CSF level of Abeta42 \<600ng/mL
• Able to ingest oral medications
• Diagnosis of mild to moderate AD according to dementia criteria outlined by McKhann et al.
• Neuroimaging (MRI or CT) consistent with the diagnosis of AD within the past year
• MMSE between 17 and 24 (inclusive) at screening
• Modified Hachinski score ≤ 4
• QTc interval 350-460ms, inclusive
• Caregiver/study partner to accompany participant to all visits and have direct contact with the participant \> 2 days/week
• Written informed consent
• Capability and willingness to comply with all study criteria
• Supervision available for study medication
• Stable medical conditions for 3 months prior to screening visit
• Stable medications for 4 weeks prior to screening visit

You may not qualify if:

• Non-AD dementia, probable AD with Down syndrome, APP, PS-1, or PS-2 mutations (known familial AD), LBD and Fronto-temporal dementia (FTD)
• History of clinically significant stroke
• 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
• Sensory impairment that would preclude participation/cooperation with the protocol
• Patients with hypokalemia, hypomagnesaemia, or long QTc syndrome.
• Concomitant drugs known to prolong the QTc interval (\>461ms) and history of cardiovascular disease, including myocardial infarction or cardiac failure, angina, arrhythmia
• Prescribed strong CYP3A4 inhibitors or a medical history of liver or pancreatic disease
• 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
• Pregnancy or possible pregnancy
• 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
• Contraindication to MRI
• Evidence of more than 4 micro hemorrhages and/or hemosiderosis by a recent (12 months) and/or the screening MRI.
• Enrolled in another active trial investigating an experimental drug or therapy for AD
• HIV positive

Sponsors & Collaborators

• Georgetown University: lead

Study Sites (1)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20057, United States

Location

Related Publications (2)

• Pagan F, Hebron M, Valadez EH, Torres-Yaghi Y, Huang X, Mills RR, Wilmarth BM, Howard H, Dunn C, Carlson A, Lawler A, Rogers SL, Falconer RA, Ahn J, Li Z, Moussa C. Nilotinib Effects in Parkinson's disease and Dementia with Lewy bodies. J Parkinsons Dis. 2016 Jul 11;6(3):503-17. doi: 10.3233/JPD-160867.

  PMID: 27434297 BACKGROUND

• Pagan FL, Hebron ML, Wilmarth B, Torres-Yaghi Y, Lawler A, Mundel EE, Yusuf N, Starr NJ, Anjum M, Arellano J, Howard HH, Shi W, Mulki S, Kurd-Misto T, Matar S, Liu X, Ahn J, Moussa C. Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease: A Phase 2 Randomized Clinical Trial. JAMA Neurol. 2020 Mar 1;77(3):309-317. doi: 10.1001/jamaneurol.2019.4200.

  PMID: 31841599 BACKGROUND

Related Links

• MEMORY DISORDERS PROGRAM Georgetown University Medical Center \& Medstar Georgetown University Hospital

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Raymond S Turner, MD, PhD

  Georgetown University

  PRINCIPAL INVESTIGATOR

• Charbel E Moussa, MBBS, PhD

  Georgetown University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Memory Disorders Program

Study Record Dates

• First Submitted: October 21, 2016
• First Posted: October 28, 2016
• Study Start: January 1, 2017
• Primary Completion: December 1, 2020
• Study Completion: March 1, 2021
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)