Evaluating the Efficacy and Safety of Nilotinib BE in Subjects With Early Alzheimer's Disease

NCT05143528 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: KFRX 2021
• Study Type: interventional
• Target: 1,275
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will investigate the safety and efficacy of a Tyrosine Kinase Inhibitor (TKI) called Nilotinib BE (bioequivalent) in individuals with Early Alzheimer's disease (EAD). This is a multi-center double blinded, Phase 3 study, that will enroll patients for three years in approximately 50 centers nationwide. The total duration of the study will be for five years.

Conditions

Alzheimer Disease

Keywords

early Alzheimer's disease; CDR; Amyloid PET; CSF Amyloid; Volumetric MRI; TAU PET

Outcome Measures

Primary Outcomes (1)

• Changes From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 72 [ Time Frame: Baseline, Week 72]

  CDR-SB integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following a systematic patient examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. Prespecified severity anchors range from none = 0, questionable = 0.5, mild = 1, moderate = 2 to severe = 3 (the personal care domain omits the 0.5 score). "Sum of boxes" scoring methodology sums the score for each of the 6 domains and provides a value ranging from 0 to 18 that can change in increments of 0.5 or greater. Higher scores indicate greater disease severity. A positive change from baseline indicates clinical decline.

  72 weeks

Secondary Outcomes (7)

• Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (14 Items) (ADAS-Cog 14) at Week 72

  72 weeks

• Change From Baseline in Mini Mental State Examination (MMSE) Score at Week 72

  72 weeks

• Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment Version) (ADCS-ADL-MCI) Score at Week 72

  72 weeks

• Blood and Cerebrospinal Fluid Biomarkers

  72 weeks.

• Tau PET imaging

  72 weeks.

Other Outcomes (2)

• Correlation of cognitive outcomes and Amyloid PET

  72 weeks

• Correlation between Amyloid and Tau with cognitive and functional outcomes

  72 weeks

Study Arms (3)

Arm A: Placebo

PLACEBO COMPARATOR

425 subjects will be randomized to the placebo group.

Drug: Placebo

Arm B: Experimental Low Dose

ACTIVE COMPARATOR

425 subjects to each of the Nilotinib BE, 84mg.

Drug: Nilotinib BE 84mg

Arm C: Experimental High Dose

ACTIVE COMPARATOR

425 subjects to each of the Nilotinib BE, 112mg.

Drug: Nilotinib BE 112 mg

Interventions

Nilotinib BE 84mg DRUG

84 mg capsule

Arm B: Experimental Low Dose

Nilotinib BE 112 mg DRUG

112 mg capsule

Arm C: Experimental High Dose

Placebo DRUG

placebo capsule

Arm A: Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of dementia due to AD
• Meet the National Institute of Aging-Alzheimer's Association (NIA-AA) core clinical criteria for dementia due to AD
• Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of 0.5 or greater at Screening and Baseline
• Have an MMSE score greater than or equals to 20 at Screening and less than or equals to 27 at Screening and Baseline
• Have a positive amyloid PET (visual reading) or positivity threshold of CSF Aβ\[1-42\] \< 660ng/ml or ptau/Aβ\[1-42\] \>0.09 using INNOTEST Enzyme-Linked ImmunoAssay (ELISA) technique (Fujirebio, Ghent, Belgium).
• QTc (corrected Q wave to the end of the T wave) interval 350-480 ms, inclusive for both men and women
• English or Spanish fluency
• Report a history of subjective memory decline with gradual onset and slow progression over the last 1 year before Screening; must be corroborated by an informant
• Positive biomarker for brain amyloid pathology as indicated by at least 1 of the following:
• PET assessment of imaging agent uptake into brain
• CSF assessment of Aβ\[1-42\] or ptau/Aβ\[1-42\] NOTE: To confirm eligibility, a positive amyloid result is needed in only 1 of the 2 procedures, including PET or CSF measurement.
• Male or female subjects aged ≥55 and ≤ 85 years, at the time of informed consent (IC)
• Body mass index (BMI) greater than 17 and less than 35 at Screening
• If receiving an approved AD treatment, such as acetylcholinesterase inhibitors (AChEIs), or memantine, or both for AD, must be on a stable dose for at least 12 weeks prior to Baseline. Treatment-naïve subjects for AD can be entered into the study. Unless otherwise stated, subjects must have been on stable doses of all other (i.e., non-AD-related) permitted concomitant medications for at least 4 weeks prior to Baseline.
• Have an identified study partner. The study partner must provide separate written IC. In addition, this person must be willing and able to provide follow-up information on the subject throughout the course of the study. This person must, in the opinion of the investigator, spend sufficient time with the subject on a regular basis such that the study partner can reliably fulfill the study requirements. A permanent study partner need not be living in the same residence with the subject. For such a study partner not residing with the subject, the investigator has to be satisfied that the subject can contact the study partner readily during the times when the study partner is not with the subject. Study partners need to participate in person for visits where clinical assessment of CDR (global and CDR-SB), ADAS-Cog, ADCS-ADL-MCI and NPI.

You may not qualify if:

• Subjects who are on anti-amyloid therapy (i.e. vaccine or antibody) or who were receiving anti-amyloid vaccines (i.e. aducunamab) or anti-tau vaccines less than 3 months before Screening.
• Women of childbearing potential (WCBP). NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
• Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the subject's AD.
• Any psychiatric diagnosis or symptoms, (e.g., hallucinations, major depression, or delusions) that could interfere with study procedures in the subject.
• Geriatric Depression Scale (GDS) score greater than or equal to 8 at Screening.
• Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (e.g., in skull and cardiac devices other than those approved as safe for use in MRI scanners).
• Evidence of other clinically significant lesions on brain MRI that could indicate a dementia diagnosis other than AD.
• Patients with hypokalemia, hypomagnesaemia, or long QT syndrome- QTc≥481 ms
• Concomitant drugs known to prolong the QTc interval and history of any cardiovascular disease, including myocardial infraction or cardiac failure, angina, arrhythmia
• Presence of cardiac conditions including:
• Cardiovascular or cerebrovascular event (e.g. myocardial infarction, unstable angina, or stroke)
• Congestive heart failure
• Second- or third-degree atrioventricular block, sick sinus syndrome, or other serious cardiac rhythm disturbances
• Any history of Torsade de Pointes
• Treatment with any of the following drugs at the time of Screening or the preceding 30 days, and/or planned use over the course of the trial:

Sponsors & Collaborators

• KeifeRx, LLC: lead
• Worldwide Clinical Trials: collaborator
• Life Molecular Imaging GmbH: collaborator
• Sun Pharmaceuticals Industries Limited: collaborator

Related Publications (1)

• Turner RS, Hebron ML, Lawler A, Mundel EE, Yusuf N, Starr JN, Anjum M, Pagan F, Torres-Yaghi Y, Shi W, Mulki S, Ferrante D, Matar S, Liu X, Esposito G, Berkowitz F, Jiang X, Ahn J, Moussa C. Nilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer's Disease. Ann Neurol. 2020 Jul;88(1):183-194. doi: 10.1002/ana.25775. Epub 2020 May 28.

  PMID: 32468646 BACKGROUND

Related Links

• Nilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer's Disease

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 Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-Blind Placebo Controlled

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: December 3, 2021
• Study Start: February 1, 2022
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: December 3, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 18 months after unblinding of the data and for a duration of 10 years.
• Access Criteria: Correspondence with the Sponsor.