A Phase 1 Double-blind, Placebo-controlled, Single- and Multiple-ascending-dose Study of KHK6640 in Alzheimer's Disease

Completed

Conditions: Alzheimer's disease
Dementia
10057167

Registration Number: NL-OMON44211

Lead Sponsor: Kyowa Hakko

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

Subjects with prodromal AD that is defined by Dubois criteria and mild to moderate AD that is defined by National Institute on Aging-Alzheimer's Association criteria will be enrolled in the study if they meet the following criteria:;1. Male or female subjects * 55 years of age at the time of enrollment;;2. CDR score of 0.5, 1.0, or 2.0;;3. Cognitive impairment episodic memory will be measured by the site using their preferred standard of measuring episodic memory;;4. CSF A* < 600 pg/mL and Tau > 300 pg/mL (by Innotest® enzyme-linked immunosorbent assay kit);;5. MMSE score > 16 at Screening;;6. Where symptomatic treatment of AD is clinically indicated, subjects must be on stable treatment (e.g., with an anticholinesterase inhibitor and/or memantine) for at least 12 weeks prior to the Screening visit;;7. Current antidepressant use must have been stable for at least 12 weeks prior to the Screening visit;;8. All other chronic use prescription medications must have been a stable dose for at least 4 weeks prior to the Screening visit;;9. Postmenopausal (defined as 12 months with no menses without an alternative medical cause, and follicle stimulating hormone test) or surgically sterile women;;10. Sexually active male subjects of child-bearing potential (and their respective partners) must agree to use two medically accepted forms of effective contraception for the entire duration of the study and for 90 days after final administration of KHK6640, or the subject must be surgically sterile (with documentation in the subject's medical records);;11. Subjects (or subjects' legal guardians/permanent caregivers according to local requirements) who have given written informed consent.

Exclusion Criteria

1. Subjects who previously received active treatment with an AD immunotherapy in an investigational study, with the exception of KHK6640 or placebo in the SAD phase;;2. Subjects who have been treated within 30 days before Screening (or 5 half-lives of the compound, if longer) with any investigational agents;;3. Subjects with a history of severe allergic, anaphylactic, or other hypersensitivity reactions, such as infusion reactions to chimeric, human, or humanized antibodies, or fusion proteins, or have known or suspected sensitivity to the investigational study drug or its excipients;;4. Subjects with a history of or presence of an active autoimmune disease and/or with an acute or chronic inflammation, and/or clinically relevant atopic condition;;5. Subjects with a history or presence of clinically significant seizures, brain trauma, transient ischemic attack, and/or cerebrovascular disease;;6. Subjects who meet National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS/AIREN) criteria for vascular dementia; ;7. Subjects with a presence of other neurodegenerative disease and/or psychiatric disorder (with the exception of successfully treated depression);;8. Subjects with any advanced, severe, progressive, or unstable disease that might interfere with the safety of the subject;;9. Subjects who have had a diagnosis of cancer or evidence of continued malignancy within 3 years of study enrollment (with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, or in situ prostate cancer with normal prostate-specific antigen [PSA] post resection);;10. Subjects who have renal, hepatic, cardiac, and/or other conditions that the Investigator considers would interfere with the study;;11. Subjects, who, for any reason, are judged by the Investigator to be inappropriate for this study, including a subject who is unable to communicate or to cooperate with the Investigator, who has/had a clinically significant illness or abnormal physical examination, psychiatric illness, disability, or social situation that may compromise the safety of the subject during the study or affect the ability of the subject to adhere to study procedures;;12. Subjects with the following hematological and chemistry laboratory values at Screening: White blood cell (WBC) count * 4000/mm3 or > 12000/mm3, Platelet count <100000/mm3, Calculated Creatinine Clearance (Cockcroft-Gault method) * 50mL/min, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >3 times the upper limit of normal (ULN), Total bilirubin 2 mg/dL, Hemoglobin (Hb) <11.0g/dL, Glycated serum hemoglobin A1c (HbA1c) * 9.0%, Diastolic blood pressure * 100 mmHg, QTc * 500 msec.;13. Subjects with a body weight <45 kg or > 120 kg;;14. Subjects who have a history of drug or alcohol abuse or dependence within the last year defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR);;15. Subjects who have any neurological condition that could be contributing to cognitive impairment above and beyond that caused by the subjects' AD;;16. Subjects who have any psychiatric diagnosis (e.g., hallucinations, major depression, or delusions) that could interfere with assesment of cognition in the subjects;;17. Subjects who have evidence of infection, tumor, or other clinically significant lesions that could

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Parameters - Various routine safety assessments to assess safety<br /><br>profile of KHK6640</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary Parameters:<br /><br>Pharmacokinetic (PK) parameters include: Cmax, AUC0-t, R, AUC0-, t1/2,<br /><br>CL and Vss<br /><br> Immunogenicity: anti-KHK6640 antibodies</p><br>