Alzheimer's disease
Conditions
Interventions
Part 1
4 cohorts in single dose IV:
- cohort 1 = 100mg or placebo
- cohort 2 = 300mg or placebo
- cohort 3 = 600mg or placebo
- cohort 4 = 1000mg or placebo
2 cohorts in single dose SC:
- cohort 1 =
Sponsors
Sanofi-aventis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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 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 tha
Exclusion criteria
Exclusion criteria: 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 scr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary and main secondary endpoints Safety: - CSF safety laboratory evaluation - Brain MRI scans - Clinical examination including neurological assessment - Local tolerability - Clinical assessment scales - Vital signs - 12-lead ECGs - Clinical laboratory evaluations - Suicidality assessment - Anti-drug antibody (ADA) assessment Pharmacokinetics: - various pharmacokinetic endpoints in plasma and CSF - Immunogenicity testing for anti-SAR228810 antibodies Pharmacodynamics: - various protein markers for Alzheimer's disease | — |
Countries
Netherlands
Outcome results
None listed