Alzheimer's Disease MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Sponsors
EIP Pharma Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women age 55 to 85 years, inclusive. 2. Willing and able to provide informed consent. 3. Must have mild cognitive impairment (MCI) or mild AD with evidence of progression (“Mild-AD”), as defined by the following: a. CDR-Global Score of 0.5 or 1.0, with CDR memory subscore of at least 0.5. b. MMSE score ranging from 20 to 28, inclusive. c. Positive biomarker for AD, as defined by a CSF Aß1-42 below the threshold and phospho-tau above the threshold for the assay utilized in the study and assessed by the central laboratory. 4. Computed tomography (CT) or magnetic resonance imaging (MRI) findings within 2 years of Screening that are compatible with AD (i.e. no other pathologic processes would potentially account for the cognitive deficit). 5. If the patient is taking a single drug for AD (e.g., donepezil or other cholinesterase inhibitors or memantine; dual therapy is excluded), he/she has been on a stable dose for at least 2 months prior to baseline, and the dose must remain unchanged during the study unless required for management of adverse events (AEs). 6. Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments. 7. Must have reliable informant or caregiver. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 76 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 76
Exclusion criteria
Exclusion criteria: 1. Evidence that the primary basis for cognitive impairment is neurodegenerative disease other than AD, including, but not limited to, vascular dementia, dementia with Lewy bodies, and Parkinson’s disease. 2. Suicidality, defined as active suicidal thoughts within 6 months before Screening or at Baseline, defined as answering yes to items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS), or history of suicide attempt in previous 2 years, or, in the Investigator’s opinion, at serious risk of suicide. 3. History of major and active psychiatric disorder, moderate to severe depressive symptoms, and or other concurrent medical condition that,in the opinion of the Investigator, might compromise safety and/or compliance with study requirements. 4. Diagnosis of alcohol or drug abuse within the previous 2 years. 5. History of cancer within the last 5 years, except basal cell carcinoma, squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years. 6.Poorly controlled clinically significant medical illness, such as hypertension (blood pressure > 180 mmHg systolic or 100 mmHg diastolic; myocardial infarction within 6 months; uncompensated congestive heart failure or other significant cardiovascular, pulmonary, renal, liver, infectious disease, immune disorder, or metabolic/endocrine disorders or other disease that would preclude treatment with p38 mitogen activated protein (MAP) kinase inhibitor and/or assessment of drug safety and efficacy. 7. History of serum B12 abnormality, anemia with hemoglobin =10 g/dL, thyroid function abnormality, electrolyte abnormality, or positive syphilis serology that have not been corrected and/or otherwise addressed. 8.History of epilepsy or unexplained seizure within the past 5 years. 9. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 × the upper limit of normal (ULN), total bilirubin >1.5 × ULN, and/or International Normalized Ratio (INR) >1.5 10. Known human immunodeficiency virus, or active hepatitis B, or active hepatitis C virus infection. 11. Subject participated in a study of an investigational drug less than 3 months or 5 half-lives of the investigation drug, whichever is longer, before enrollment in this study. 12. Male subjects with female partners of child-bearing potential who are unwilling or unable to adhere to contraception requirements specified in the protocol. 13. Female subjects who have not reached menopause or have not had a hysterectomy or bilateral oophorectomy/salpingo-oophorectomy. • If a female subject reached menopause within the previous year, a pregnancy test must be performed during Screening and the subject must be willing to adhere to the contraception requirements specified in the protocol Such subjects with a positive urine or serum pregnancy test are not eligible for study participation. 14. Requires concomitant use of strong cytochrome P450 (CYP) 3A4 inhibitors or anti-tumor necrosis factor-alpha therapies during study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the effects of administration of neflamapimod (VX-745) for 24-weeks on immediate and delayed recall aspects of episodic memory, as assessed by the Hopkins Verbal Learning Test – Revised (HVLT-R) in patients with mild Alzheimer’s disease (AD).; Secondary Objective: •To evaluate effects of neflamapimod on immediate and delayed recall of Logical Memory (LM), Verbal Paired Associates (VPA) and Visual Reproduction (VR) components of the Wechsler Memory Scale® (WMS). • To evaluate effects of neflamapimod on the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) and Mini-Mental State Examination (MMSE). • To evaluate the effects of neflamapimod on AD-related cerebrospinal fluid (CSF) biomarkers (total tau, phospho-tau, amyloid-beta peptides, neurogranin and neurofilament light chain). ;Primary end point(s): Combined change in z-scores of total recall and delayed recall on the HVLT-R in neflamapimod-treated subjects compared to placebo-recipients.;Timepoint(s) of evaluation of this end point: Timepoints at which HVLT-R will be administered Day 1 (V3), Day 42 (V5), Day 84 (V6), Day 168 (V8) or Early Term (V9) - end of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Change in WMS immediate and delayed recall composites in neflamapimod -treated subjects compared to placebo-recipients. •Change in CDR-SB in neflamapimod -treated subjects compared to placebo-recipients. •Change in CSF biomarkers (total tau, p-tauR181R, AßR1 40R, AßR1-42, neurogranin, neurofilament light chain) in neflamapimod -treated subjects compared to placebo-recipients. ; Timepoint(s) of evaluation of this end point: WMS: Day 1 (V3), Day 42 (V5), Day 84 (V6), Day 168 (V8) or Early Term (V9) - end of treatment CDR: Screening (V1), Day 84 (V6), Day 168 (V8) or Early Term (V9) - end of treatment CSF: Screening (V2), Day 168 (V8) or Early Term (V9) - end of treatment | — |
Countries
Czech Republic, Denmark, Netherlands, United Kingdom, United States
Contacts
Public ContactProject Management
Worldwide Clinical Trials Limited
Outcome results
None listed