MCLENA-1: A Clinical Trial for the Assessment of Lenalidomide in Amnestic MCI Patients

Inclusion Criteria:

• In order to be eligible for this study, subjects must meet the following inclusioncriteria:

1. Male or female outpatients.

2. At least 50 years of age, but less than 90 (89 at time of screening).

3. Females must be surgically sterile (bilateral tubal ligation, oophorectomy, orhysterectomy) or postmenopausal for 2 years (no women at risk of pregnancy willbe accepted in this study).

4. Must have been diagnosed with amnestic MCI based on the most recent NIA-AAcriteria (Albert et al., 2011), i.e. at both the screening and baseline visits (visits 1 and 2) have a documented Mini Mental State Exam (MMSE) score between 22-28.

5. CT or MRI scan of the brain obtained during the course of the dementia must beconsistent with the diagnosis and show no evidence of significant focal lesionsor of pathology which could contribute to dementia. If neither a CT nor an MRIscan is available from the past 12 months, a CT scan fulfilling therequirements must be obtained before randomization.

6. Vision and hearing must be sufficient to comply with study procedures.

7. Be able to take oral medications.

8. Hachinski ischemic score must be ≤ 4.

9. Geriatric depression scale must be ≤ 10.

10. Can be on stable doses of a cholinesterase inhibitor and/or memantine as longas it is stable for at least 90 days before the Baseline (Week 00) and isexpected to remain on a stable dose for the remainder of the study period; orhave demonstrated intolerance to or lack of efficacy from these medications.

11. Must have a collateral informant/study partner who has significant directcontact with the patient at least 10 hours per week and who is willing toaccompany the patient to all clinic visits and to be present during alltelephone visits/interviews.

12. If the patient has a legally authorized representative (LAR), the LAR mustreview and sign the informed consent form. If the patient does not have an LAR,the patient must appear able to provide informed consent and must review andsign the informed consent form. In addition, the patient's informant/studypartner (as defined above) must sign the informed consent form. If the LAR andthe patient's informant /study partner is the same individual, he/she shouldsign under both designations.

13. Must be able to attend all study visits indicated in the schedule of visits.

14. Patients with stable prostate cancer may be included at the discretion of theMedical Monitor.

15. Medical records must document evidence of amnestic MCI with 1 of the following:MRI with hippocampal volume in the 5th percentile or lower for age, Amyloid PETpositive at SUVr ≥ 1.05, CSF Tau profile with ATI lower than 1.0, FDG PETshowing hypometabolism in the parietal temporal regions, or geneticconfirmation of APOE4 (heterozygous or homozygous).

Exclusion Criteria:

• Subjects will be excluded if they have any of the condition listed below:

1. Current evidence or history within the last 3 years of a neurological orpsychiatric illness that could contribute to dementia, including (but notlimited to) epilepsy, focal brain lesion, Parkinson's disease, seizuredisorder, head injury with loss of consciousness

2. DSM IV criteria for any major psychiatric disorder including psychosis, majordepression and bipolar disorder.

3. Known history or self-reported alcohol or substance abuse.

4. Isolated living circumstances which would prohibit a study partner fromproviding sufficient and credible information about the participant.

5. Poorly controlled hypertension.

6. History of myocardial infarction or signs or symptoms of unstable coronaryartery disease within the last year (including revascularizationprocedure/angioplasty).

7. Severe pulmonary disease (including chronic obstructive pulmonary disease)requiring more than 2 hospitalizations within the past year.

8. Untreated sleep apnea.

9. Any thyroid disease (unless euthyroid or on treatment for at least 6 monthsprior to screening).

10. Active neoplastic disease (except for skin tumors other than melanoma).Patients with a history of prior malignancy are eligible provided they weretreated with curative intent and (i) do not require any longer any activetherapy; (ii) being considered in complete remission; and (iii) after theMedical Monitor's assessment/approval of each case.

11. History of multiple myeloma.

12. Absolute neutropenia of <750mm3, or history of neutropenia.

13. History of or current thromboembolism (including deep venous thrombosis).

14. Any clinically significant hepatic or renal disease (including presence ofHepatitis B or C antigen/antibody or an elevated transaminase levels of greaterthan two times the upper limit of normal (ULN) or creatinine greater than 1.5 xULN).

15. Clinically significant hematologic or coagulation disorder including anyunexplained anemia or a platelet count less than 100,000/μL at screening.

16. Use of any investigational drug within 30 days or within five half-lives of theinvestigational agent, whichever is longer.

17. Use any investigational medical device within two weeks before screening orafter end of the present study.

18. Females who are at risk of pregnancy or are of child bearing age.

19. Any other disease or condition that, in the opinion of the investigator, makesthe patient unsuitable to participate in this clinical trial.

20. Unwilling or unable to undergo MRI and PET imaging.

21. Cardiac pacemaker or defibrillator or other implanted device.

22. In the opinion of the Investigator, participation would not be in the bestinterest of the subject.