A Study to Evaluate Albumin and Immunoglobulin in Alzheimer's Disease

A clinical trial comprised of 350 subjects with probable mild to moderate Alzheimer's Disease
(AD) will be conducted primarily to determine whether plasmapheresis with infusion of human
albumin combined with Intravenous immunoglobulin (IVIG) is able to modify patient's
cognitive, functional, behavioral and global domains. There will be 3 treatment groups and
one control group. The subjects will be randomized in a 1:1:1:1 proportion.

Main Inclusion Criteria:

1. Males or females between 55-85 years of age at the time of signing of the informed
consent document.

2. A diagnosis of Alzheimer's disease (NINCDS-ADRDA criterion), and MMSE score between
>/=18 and
3. Current stable treatment with AChEIs and/or memantine for the previous three months.

4. The patient and a close relative or the legal representative must read the patient
information sheet, agree to participation in the trial, and then sign the informed
consent document (the patient personally and the close relative/legal representative).

5. The patient must be able to follow the study protocol, receive the treatment in the
established time period, and continue during the follow-up interval.

6. A brain CAT or MRI study obtained in the 12 months prior to recruitment, showing the
absence of cerebrovascular disease, should be available. Nevertheless, it is possible
to use the MRI obtained during the screening period to rule out any cerebral vascular
disease.

7. A stable care taker must be available, and must attend the patient study visits.

Main Exclusion Criteria:

1. Any contraindication for plasma exchange due to behavioral disorders or abnormal
coagulation parameters, such as for example:

- Hypocalcemia (Ca++ < 8.7 mg/dL)

- Thrombocytopenia (<100,000/µL)

- Fibrinogen <1.5 g/L)

- Prothrombin time (Quick) p<60% versus control (INR >1.5)

- Beta-blocker treatment and bradycardia <60/min)

- Treatment with angiotension-converting enzyme inhibitors (ACEIs) (increased risk
of allergic reactions)

2. Hemoglobin < 10 mg/dL

3. Difficult venous access precluding plasma exchange.

4. A history of frequent adverse reactions (serious or otherwise) to blood products.

5. Hypersensitivity to albumin or allergies to any of the components of Albutein® 5%.

6. History of immunoglobulin A (IgA) deficiency.

7. Known allergies to Flebogamma® DIF components such as sorbitol.

8. History of thromboembolic complications of intravenous immunoglobulins.

9. Plasma creatinine > 2 mg/dl.

10. Uncontrolled high blood pressure (systolic blood pressure of 160 mmHg or higher and/or
diastolic blood pressure of 100 mmHg or higher despite treatment during the last 3
months).

11. Liver cirrhosis or any liver problem with GPT > 2.5 x ULN, or bilirubin > 2 mg/dL.

12. Heart diseases, as evidenced by myocardial infarction, severe or unstable angina, or
heart failure (New York Association Class II, III or IV) in the past 12 months.

13. Participation in other clinical trials, or the receiption of any other investigational
drug in the three months prior to the start of the study.

14. Any condition complicating adherence to the study protocol (illness with less than one
year of expected survival, known drug or alcohol abuse, etc.).

15. Pregnant or nursing women or women not using effective contraceptive methods for at
least one month after plasma exchange.

16. Fewer than six years of education (exclusion criteria under medical criterion).

17. Fewer than three months with stable treatment for behavioral disorders or insomnia.