| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Early Alzheimer's Disease |
|
| E.1.1.1 | Medical condition in easily understood language |
| Alzheimer's Disease (AD) is a neurodegenerative disease associated with aging. AD patients suffer from cognition deficits and memory loss as well as behavioral problems such as anxiety. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10074616 |
| E.1.2 | Term | Prodromal Alzheimer's disease |
| E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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. |
|
| E.2.2 | Secondary objectives of the trial |
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 Aβ species (Aβ1-37, Aβ1-38, Aβ1-40, Aβ1-42) and soluble amyloid precursor protein (sAPP) fragments (sAPPα, sAPPβ, 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 Aβ1-40 and sAPP fragments (sAPPα, sAPPβ, 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 Aβ species and sAPP fragments with safety in subjects in the early AD spectrum. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 least weekly contact with the subject (contact can be in-person, via telephone or electronic communication). The informant must have sufficient contact such that the investigator feels he/she can provide meaningful information about the subject’s daily function.
11. Subject must be able to be compliant with self-administration of medication
12. Subject must be able to swallow drug as a whole.
13. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
14. Subject must sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. |
|
| E.4 | Principal 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 planned during the time the subject is expected to participate in the study or within 4 weeks after the last dose of study drug administration.
27. Subject has a history of spontaneous, prolonged or severe bleeding.
28. Subject has donated one or more units of blood or acute loss of an equivalent amount of blood within 90 days prior to study drug administration.
29. Subject has a topical infection or local dermatological condition at the puncture site prior to puncture that may compromise the lumbar puncture.
30. Subject has a pigmentation abnormality of the skin such as vitiligo.
31. Subject has signs of increased intracranial pressure.
32. Subject has a current or recent history of clinically significant suicidal ideation within the past 6 months, or a history of suicidal behavior within the past year.
33. Subject is an employee of the investigator or study site, as well as family members of the employees or the investigator.
34. Subject has any condition that would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements.
35. Only for subjects who will have an optional PET scan performed at screening: Subject has past or planned exposure to ionizing radiation that in combination with the planned administration with study amyloid PET ligand would result in a cumulative exposure that exceeds local recommended exposure limits.
36. Subject is unable to comply with the study-specific requirements. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The assessment of specified safety parameters of JNJ-54861911 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| The assessment of specified pharmacokinetic parameters of JNJ-54861911 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 22 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
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