A multi-center, parallel-group, double-blind, placebo-controlled single and multiple dose escalation study to assess the safety and tolerability and the pharmacokinetic properties of SAR228810 given as IV infusion or as SC injection in patients with mild to moderate Alzheimer*s Disease.

Demography
I 01. Male or female patients with mild to moderate Alzheimer*s disease, aged between 50 and
85 years inclusive.
I 02. Body weight between 50.0 and 110.0 kg inclusive.
Health Status
I 03. Meets NINCDS-ADRDA criteria for probable Alzheimer*s disease [National Institute of
Neurologic and Communicative Disorders and Stroke - AD and Related Disorders
Association]
I 04. mini-mental state examination (MMSE) score of 16*28 (inclusive)
I 05. in reasonable and stable health state for Alzheimer*s patients of this age and stage of
disease as assessed by a comprehensive clinical assessment (detailed medical history and
complete physical examination).
I 06. Normal vital signs after 10 minutes resting in supine position:
- 95 mmHg < systolic blood pressure < 180 mmHg
- 45 mmHg < diastolic blood pressure < 95 mmHg
- 50 bpm < heart rate < 100 bpm
I 07. Normal standard 12-lead ECG after 10 minutes resting in supine position;
120 ms < PR < 220 ms, QRS < 120 ms, QTc <= 475 ms.
I 08. Laboratory parameters within the normal range, unless the Investigator considers an
abnormality to be clinically irrelevant for Alzheimer*s patients of this age and stage of
disease.
I 09. If female, patient must use a double contraception method, except if she is sterilized for
more than 3 months or postmenopausal. The accepted double contraception methods
include use of a highly effective method of birth control (intra-uterine device or hormonal
contraception) in addition to one of the following contraceptive options: 1) condom, in addition to spermicide; 2) diaphragm or cervical/vault cap, in addition to spermicide.
Menopause is defined as over the age of 60 years, or between 45 and 60 years being
amenorrheic for at least 2 years with plasma FSH level > 30 UI/L.
For sexually active male subjects with partners of childbearing potential: accepting to use a
double effective method of contraception during the study and for 16 weeks after the last
dosing. Accepted double contraception algorithms: (condom associated with spermicide)
plus (occlusive cap or intrauterine device or hormonal contraceptive).
For sexually active male subjects whose partners are pregnant or not of childbearing
potential: accepting to use condoms from the first study drug administration up to 16
weeks after last dosing.
Regulations
I 10. Having given written informed consent prior to any procedure related to the study.
Depending on national law the informed consent of a patient*s caregiver has also to be
obtained where applicable.
For a patient who is unable to understand the patients* study information or is unable to
give informed consent due to his/her cognitive status, either written informed consent
could be obtained from the patient*s legal representative if this is in accordance with all
legislation for clinical trials in the respective country, or the patient must not be included.
I 11. Covered by a Health Insurance System where applicable, and/or in compliance with the
recommendations of the national laws in force relating to biomedical research.
I 12. Not under any administrative or legal supervision (eg detainees or mentally ill).
For special cases of AD refer to I 10.
Specific to the study
I 13. MRI consistent with Alzheimer*s disease, not indicating any other cause for dementia
symptoms than Alzheimer*s disease.
I 14. The Alzheimer's type of the dementia must have been confirmed before randomization of a
patient by specific CSF biomarkers (Aβ1-42 and/or p-Tau) or by brain amyloid PET
scanning.
I 15. Rosen Modified Hachinski Ischemic score <= 4
I 16. If on symptomatic treatment for Alzheimer*s disease (AChEI or/and memantine), must be
stable in the last 30 days before screening

Medical history and clinical status
E 01. clinically significant neurological disease other than Alzheimer*s disease;
E 02. had a major psychiatric disorder;
E 03. had a history of stroke, seizures, brain neoplasms, brain surgery, or any cerebrovascular
disorder (including TIA);
E 04. Any presence of severe, uncontrolled and/or unstable cardiovascular, cerebrovascular,
pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological,
endocrine, autoimmune, osteo-muscular, articular, systemic, ocular, gynecologic (if
female), malignant neoplastic, or infectious disease, or signs of acute illness that would
increase significantly the risks for the patient in participating in this study.
E 05. History or presence of severe, uncontrolled and/or unstable angiopathy or vasculitis.
E 06. History of deep vein thrombosis or pulmonal embolism or
familial predisposition for deep vein thrombosis or pulmonal embolism.
E 07. Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a
month).
E 08. Blood donation, any volume, within 2 months before inclusion.
E 09. Symptomatic postural hypotension, whatever the decrease in blood pressure, or
asymptomatic postural hypotension defined by a decrease in systolic blood pressure
>=20 mmHg within 3 minutes when changing from the supine to the standing position.
E 10. Presence or history of drug hypersensitivity, auto-immune or allergic disease diagnosed
and treated by a physician.
E 11. History or presence of drug or alcohol abuse (alcohol consumption >40 grams per day).
E 12. Excessive consumption of beverages with xanthine bases (>4 cups or glasses per day).
E 13. If female, pregnancy (defined as positive β-HCG blood test), breast-feeding.
Interfering substance
E 14. Currently taking anticonvulsants, antiparkinsonians, antipsychotics, anticoagulants (e.g.
cumarines and related drugs, direct thrombin inhibitors, Factor Xa inhibitors), P2Y12
receptor inhibitors (e.g. clopidogrel) or narcotic drugs, recent immunosuppressive or
cancer chemotherapy drugs, or cognitive enhancers.
Concomitant therapies that are allowed if given at a stable dose for at least 30 days before
screening are:
acetylcholinesterase inhibitors and/or memantine; SSRI antidepressants (no tricyclics);
acetyl salycilic acid (ASA) at a dose <= 160 mg/day; Vitamin B12; lipid lowering drugs;
antihypertensives; zaleplon, zolpidem and zopiclone; low-dose benzodiazepine treatment.
Other stable concomitant medications may be allowed on an individual basis if the
investigator has no safety concerns.
E 15. Having had a vaccination within less than 2 weeks prior to or after a dosing during the
scheduled treatment periods
E 16. Having taken part in a clinical trial with a non-approved vaccination as investigational
product in the past
General conditions
E 17. Any patient who, in the judgment of the Investigator, is likely to be non-compliant during
the study, or unable to cooperate because of a language problem or poor mental
development.
E 18. Any patient in the exclusion period of a previous study according to applicable regulations.
In case of previous participation in a trial with monoclonal antibodies, the exclusion period
should be not shorter than 6 months between the last visit of the previous study and
screening visit of the present study.
E 19. Any patient that has been administered other anti-Aβ monoclonal antibodies or Aβ
vaccines in other clinical trials
E 20. Any patient who cannot be contacted in case of emergency.
E 21. Any patient who is the Investigator or any sub-investigator, research assistant, pharmacist,
study coordinator, or other staff thereof, directly involved in the conduct of the protocol.
Biological status
E 22. Positive reaction to any of the following tests: hepatitis B surface (HBs Ag) antigen, antihepatitis
C virus (anti-HCV2) antibodies, anti-human immunodeficiency virus 1 and 2
antibodies (anti-HIV1 and anti HIV2 Ab).
E 23. Positive results on urine drug screen (amphetamines/methamphetamines, barbiturates,
benzodiazepines, cannabinoids, cocaine, opiates).
E 24. Positive alcohol test.
Specific to the study
E 25. Cerebrospinal fluid (CSF): CSF/Serum albumin ratio, CSF IgG and IgM indices and/or
CSF cell counts indicating CNS diseases or injuries other than Alzheimer*s disease, e.g.
stroke, neuroborreliosis, Guillain-Barré syndrome, multiple sclerosis, vascular dementia, or
other infectious or inflammatory CNS diseases.
E 26. Brain MRI at screening/baseline revealing
- more than 4 cerebral microhemorrhages (regardless of their anatomical location or
diagnostic characterization as *possible* or *definite*), or
- a single area of superficial siderosis, or
- evidence of a prior macrohemorrhage
E 27. Presence of any contraindication for CSF sampling by lumbar puncture, including
coagulopathy and thrombocytopenia,
E 28. Presence of any contraindication to have MRI scans performed (e.g. pacemaker, vascular
clips etc.)
E 29. History or presence of clinically relevant cardiac disease. If considered to be indicated by
the investigator, a consultation of a cardiologist has to be performed prior to inclusion/start
of dosing.