Early Alzheimer's Disease MedDRA version: 18.1 Level: PT Classification code 10074616 Term: Prodromal Alzheimer's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: JNJ-54861911
Product Code: JNJ-54861911
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: not yet available
CAS Number: 1200493-78-2
Current Sponsor code: JNJ-54861911
Other d
Sponsors
Janssen-Cilag International N.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each potential subject must satisfy all of the following criteria to be enrolled in the study. 1. Subjects in the early AD spectrum must have a global CDR score of 0 (asymptomatic at risk for AD) to 0.5 (pAD) inclusive 2. Subjects with pAD: Subject must be a man or woman between 50 and 85 years of age, inclusive. Subjects who are asymptomatic at risk for AD: Subject must be a man or woman between 65 and 85 years of age, inclusive. If rolling over from study 54861911ALZ1005 subjects aged 60 to 64 maybe included. 3. Subjects must have had sufficient education or work experience to exclude mental retardation and must be able to read and write. 4. Subjects must have evidence of amyloid pathology by means of either: a) low CSF Aß1-42 levels at screening b) a positive amyloid PET scan at screening (depending on the site’s PET capability) by visual read 5. Subjects must have a body mass index (BMI=weight/height²) between 18 and 35 kg/m2, inclusive, at screening. 6. Before randomization, a woman must be not of childbearing potential: postmenopausal (=50 years of age with amenorrhea for at least 12 months; permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy)); or otherwise be incapable of pregnancy. In case of questionable status qualified personal of the sponsor should be consulted to decide on the potential for inclusion of the subject. 7. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control e.g., either 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, and all men must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug. In addition, their female partners, if of childbearing potential, should also use an appropriate method of birth control for at least the same duration. Effective methods of contraception include prescription oral contraceptives, contraceptive injections, intrauterine device, double barrier method, contraceptive patch. 8. Subjects must be otherwise healthy for their age group or medically stable with or without medication on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening or at baseline. If there are abnormalities, they must be consistent with the underlying illness in the study population and not a potential cause of cognitive impairment, with written concurrence with the sponsor's medical monitor. 9. Subjects must be otherwise healthy or medically stable on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel [including liver enzymes, other specific tests], hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant, to be appropriate and reasonable for the population under study and not to be a potential cause of cognitive impairment, with written concurrence with the sponsor's medical monitor. This determination must be recorded in the subject’s source documents and initialed by the investigator. 10. Subjects must have a reliable informant (relative, partner, or friend). The informant must be willing to participate as a source of information and has at lea
Exclusion criteria
Exclusion criteria: Any potential subject who meets any of the following criteria will be excluded from participating in the study. 1. Subject has evidence of any brain disease, other than potential very early signs of AD or typical age-related changes or any other abnormality that could explain a possible cognitive deficit. 2. Subject has met criteria for dementia or has a degenerative brain disorder that can cause dementia. 3. Subject has evidence of familial autosomal dominant AD. 4. Subject has a history of or current thyroid disease, thyroid dysfunction and is currently untreated for it. 5. Subject has a vitamin B12 or folic acid deficiency. 6. History or presence of significant depression as defined by the most current DSM criteria. 7. Subject has chromosome 21 trisomy (Down Syndrome); 8. Subject has a history of or current evidence of neurosyphilis 9. Subject has any contra-indications for MRI. 10. Subject has a clinically significant abnormal physical- or neurological examination, vital signs at screening or baseline. 11. Subject has, in the opinion of the investigator, a clinically significant 12-lead ECG at screening or baseline. In case of triplicate ECG recordings, 2 out of 3 individual recordings must have a QTc below 450 msec. 12. Subject has a relevant history of or current neurological disease which in the opinion of the investigator may make interpretation of possible new neurological signs or symptoms difficult. 13. Subject has a history of or current liver or renal insufficiency; clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, rheumatologic, psychiatric, or metabolic disturbances. 14. Subject has a 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 is considered cured with minimal risk of recurrence). 15. Subject has a history of epilepsy or fits or unexplained black-outs other than vasovagal collapse within 10 years before screening. 16. Subject has current anemia. 17. Subject has a history of positive tests for hepatitis B surface antigen or hepatitis C antibody, or other clinically active liver disease. 18. Subject has a history of human immunodeficiency virus (HIV) antibody positive. 19. Subject has a history of drug or alcohol abuse according to most current DSM criteria within 6 months before Screening or positive test result(s) for alcohol or other drugs of abuse at Screening (except if related to current treatment e.g., benzodiazepines). 20. Subject has taken any disallowed therapies. 21. Subject has a clinically significant acute illness within 7 days prior to study drug administration. 22. Subject has known allergies, hypersensitivity, or intolerance to JNJ-54861911 or its excipients. 23. Subject has received an investigational drug (excluding the use of JNJ-54861911 in previous studies). 24. Subject is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug. 25. Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject or that could prevent, limit, or confound the protocol-specified assessments. 26. Subject has had major surgery, (e.g., requiring general anesthesia) within 8 weeks before screening, or will not have fully recovered from surgery, or has surgery plan
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The assessment of specified safety parameters of JNJ-54861911;Timepoint(s) of evaluation of this end point: 6 months;Main Objective: The primary objective of this study is to investigate the longer-term safety and tolerability of JNJ-54861911 during 6 months of treatment in subjects in the early (predementia) AD spectrum.;Secondary Objective: The secondary objectives of this study are: • To assess the relationship of dose and exposure of JNJ-54861911 with safety in subjects in the early AD spectrum. • To evaluate the pharmacokinetics over time of JNJ-54861911 in subjects in the early AD spectrum. • To assess changes in CSF Aß species (Aß1-37, Aß1-38, Aß1-40, Aß1-42) and soluble amyloid precursor protein (sAPP) fragments (sAPPa, sAPPß, total sAPP) at 6 months of treatment with JNJ-54861911 compared to placebo in subjects in the early AD spectrum. • To assess changes in plasma Aß1-40 and sAPP fragments (sAPPa, sAPPß, total sAPP) at 6 months of treatment with JNJ-54861911 compared to placebo in subjects in the early AD spectrum. • To assess the relationship of changes in CSF and plasma Aß species and sAPP fragments with safety in subjects in the early AD spectrum. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The assessment of specified pharmacokinetic parameters of JNJ-54861911;Timepoint(s) of evaluation of this end point: 6 months | — |
Countries
Belgium, Germany, Netherlands, Spain, Sweden
Contacts
Public ContactClinical Registry Group
Janssen Pharmaceutica N.V.
Outcome results
None listed