Evaluation of Safety & Tolerability of Multiple Dose Regimens of CHF 5074

Study Overview
=================
Brief Summary
-----------------
To evaluate the safety and tolerability of ascending oral doses of CHF 5074 administered once per day for up to 12 weeks to patients with mild cognitive impairment.

Official Title
-----------------
A Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Tolerability of Multiple Dose Regimens of CHF 5074 and to Explore the Effects in Patients With Mild Cognitive Impairment

Conditions
-----------------
Alzheimer's Disease

Intervention / Treatment
-----------------
* Drug: CHF 5074 1x
* Drug: CHF 5074 2x
* Drug: CHF 5074 3x
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of amnestic or non-amnestic Mild Cognitive Impairment. Mini-Mental State Examination score higher than 24 at screening. MRI scan of the brain at screening with fluid-attenuation inversion recovery (FLAIR) and T2*-weighted gradient-recalled-echo (GRE) sequences. Exclusion Criteria: Diagnosis of Alzheimer's disease according to the (DSM-IV-TR) or NINCDS-ADRDA criteria. Any medical condition that could explain the patients cognitive deficits. CT or MRI brain imaging results obtained within 12 months prior to baseline showing evidence of infection, infarction, or focal lesions of clinical significance MRI scan at screening showing more than 4 cerebral microhemorrhages (lesions with diameter ≤ 10 mm). Geriatric Depression Scale (30-point scale) score > 9 at screening. History of stroke. Modified Hachinski ischemic scale score > 4 at screening. Women of childbearing potential. Vitamin B12 or folate deficiency. Diagnosis of schizophrenia or recurrent mood disorder (including unipolar and bipolar disorders) within 3 years of screening. Current diagnosis of peptic ulcer or gastrointestinal bleeding within the last year and/or chronic inflammatory bowel disease. Concomitant use of donepezil at doses > 5 mg/day or other cholinesterase inhibitors (rivastigmine or galantamine) at any dose. Concomitant use of memantine at dose > 20 mg/day. Concomitant use of psychoactive drugs (sedatives, hypnotics, etc).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHF 5074 1x<br>oral tablet, multidose | Drug: CHF 5074 1x<br>* oral tablet, 1x, once a day in the morning for 12 weeks<br>|
| Experimental: CHF 5074 2x<br>oral tablet, multidose | Drug: CHF 5074 2x<br>* oral tablet, 1x, once a day in the morning for 4 weeks, followed by oral tablet, 2x, once a day in the morning for 8 weeks<br>|
| Experimental: CHF 5074 3x<br>oral tablet, multidose | Drug: CHF 5074 3x<br>* oral tablet, 1x, once a day in the morning for 4 weeks, followed by oral tablet, 2x, once a day in the morning for 4 weeks, followed by oral tablet, 3x, once a day in the morning for 4 weeks<br>|
| Placebo Comparator: Placebo<br>placebo, oral tablet, multidose | Drug: Placebo<br>* oral tablet, once a day in the morning for 12 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in ∆sCD40L Levels Between CHF 5074 Doses and Placebo at Any Specific Time Point | To assess if there were differences in ΔsCD40L levels between CHF 5074 doses and placebo | up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of Trough CHF 5074 Plasma Levels | evaluate the pharmacokinetics (PK) of CHF 5074 in patients with MCI. | Days 85 | 
| Changes in Plasma ΔTNFα Concentrations |  | 29 days |