A 2-Part Randomized, Placebo-Controlled, Double-Blind, Single and Multiple Ascending Dose Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-63733657 in Healthy Subjects and Subjects With Alzheimer*s Disease

Completed

Conditions: Alzheimers Disease
10029305

Registration Number: NL-OMON48645

Lead Sponsor: Janssen-Cilag

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 36

Inclusion Criteria

Each potential subject must satisfy all of the following criteria to be enrolled in the study: ;1. Male or female. Note: equal gender representation is preferred when feasible. ;2. 55 to 75 years of age, inclusive.;3.1. body mass index (BMI) between 18 and 35 kg/m2, inclusive (BMI = weight/height2) and
body weight greater than 40 kg but less than 110 kg at screening.;4.1 otherwise healthy for their age group (Part 1 and Part 2-HS) or medically stable (Part 2 AD) on the basis of physical examination, medical history, vital signs, and 12 lead ECG performed at screening or admission to the clinical unit. If there are abnormalities, they must be consistent with the underlying illness or age of the study population and not deemed clinically unstable. This determination must be recorded in the subject's source documents and initialed by the investigator;5. 1 otherwise healthy for their age group (Part 1 and Part 2-HS) or medically stable (Part 2 AD) on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel (including liver enzymes), hematology, coagulation or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the investigator.

6. Women must not be of childbearing potential defined as: ;• Postmenopausal: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level at screening (>40 international units per liter (IU/L) or milli-international units per milliliter [mIU/mL]) in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy, however in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.;• Permanently sterile: Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy.;Note: If reproductive status is questionable, additional evaluation will be considered;7. During the study and up to 16 weeks after receiving the last dose of study drug a man:;• who is sexually active with a woman of childbearing potential and has not had vasectomy must agree to use a barrier method of contraception (e.g., condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository). In addition, their female partner should also use a highly effective method of birth control (e.g. hormonal contraception) for at least the same duration.;• who is sexually active with a woman who is pregnant must use a condom. ;• must agree not to donate sperm.;8. must be willing to adhere to the prohibitions and restrictions specified in this protocol.;9. must sign an informed consent form (ICF) (or their legally acceptable representative;depending on disease state) indicating that he or she understands the purpose of, and;procedures required for, the study and is willing to participate in the study.;4.1.2 Specific Inclusion Criteria Part 2;Each potential subject enrolled in Part 2-AD must satisfy all of the following specific criteria in addition to the general criteria to be enrolled in the study:;10. Clinical Dementia Rati

Exclusion Criteria

Any potential subject who meets any of the following criteria will be excluded from participating in the study:;1.1 history of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic (including but not limited to neurodegenerative disease (excluding AD for Part 2-AD) [e.g., Parkinson*s disease], seizure disorders, transient ischemic attacks, etc.), hematologic (including coagulation disorders), rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness that the Investigator considers should exclude the subject.
2.1 relevant history of or current neurological disease (other than prodromal AD or mild AD for Part 2-AD), which in the opinion of the investigator may make interpretation of possible new neurological signs or symptoms difficult
3.1. Positive result on hepatitis B surface antigen (HBsAg), hepatitis B core antibody
(HBcAb), hepatitis C antibody (anti-HCV), or any other clinically active liver disease at
screening (per screening evaluations)
4. History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening (per screening evaluations)
5. Any contra-indications for magnetic resonance imaging (MRI) (prostheses, implants, claustrophobia, pacemakers, etc)
6. Evidence of any brain disease other than potential very early signs of AD (e.g., mild hippocampal atrophy) or typical age-related changes (e.g., mild white matter hyperintensity on MRI), that could explain the cognitive deficit (including, but not limited to vascular encephalopathy or strokes, as imaged by cerebral MRI and Major Depression, as defined by DSM (current edition) criteria. The screening MRI scan shall be interpreted by a local radiologist and investigator for exclusionary findings prior to enrolling the subject.
7. history of malignancy within 5 years before screening (exceptions are squamous and
basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that
in the opinion of the investigator, with written concurrence with the sponsor's medical
monitor, is considered cured with minimal risk of recurrence).
8. history of drug or alcohol use disorder according to DSM (latest edition) criteria within
6 months before Screening or has a positive test result(s) for alcohol and/or drugs of
abuse (including: opiates (including methadone), cocaine, amphetamines,
methamphetamines, cannabinoids, barbiturates, and benzodiazepines) at screening or
admission to the clinical unit.
9.1. drinks, on average, more than 8 cups of tea/coffee/cocoa/cola/caffeinated beverages
(e.g., energy drink) per day for Part 1 subjects.
10. clinically significant acute illness within 7 days prior to study drug administration.
11.1. smokes cigarettes (or equivalent) and/or has used nicotine based products within 3 months prior to study drug administration for Part 1 subjects.
12. man who plans to father a child while enrolled in this study or within 13 weeks after the
last dose of study drug.
13. history of clinically significant drug and/or food allergies.
14. known or suspected intolerance or hypersensitivity to any biologic medication or
known allergies or clinically significant reactions to human proteins, monoclonal
antibodies or antibody fragments, or any of the excipients of JNJ-63733657 (refer to
Investigator's Br

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1. Assess the safety and tolerability of JNJ-63733657 following single<br /><br>ascending IV dose administration in healthy subjects (Part 1).<br /><br>2. Assess the safety and tolerability of JNJ-63733657 following multiple<br /><br>ascending IV dose administrations in subjects with prodromal or mild AD; Part<br /><br>2).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. Pharmacokinetics of JNJ-63733657 in Serum en CSF (Part 1)<br /><br>2. Immunogenicity of JNJ-63733657 in Serum (Part 1)<br /><br>3. Pharmacodynamics of JNJ-63733657 in CSF (Part 1)<br /><br>4. Pharmacokinetics of JNJ-63733657 in Serum en CSF (Part 2)<br /><br>5. Immunogenicity of JNJ-63733657 in Serum (Part 2)<br /><br>6. Pharmacodynamics of JNJ-63733657 in CSF (Part 2)</p><br>