E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Early Alzheimer's Disease (Predementia) |
Enfermedad de Alzheimer temprana (Pre-demencia) |
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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. |
EA es una enfermedad neurodegenerativa asociada con la edad. Pacientes con EA sufren déficit de conocimiento y pérdida de memoria así como problemas de conducta como ansiedad. |
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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 | 17.0 |
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 |
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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. |
El objetivo principal de este estudio consiste en investigar la seguridad y tolerabilidad a más largo plazo de JNJ-54861911 durante 6 meses de tratamiento en pacientes con EA temprana (pre-demencia). |
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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 Aß species (Aß1-37, Aß1-38, Aß1-40, Aß1-42) and soluble amyloid precursor protein (sAPP) fragments (sAPP?, 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 (sAPP?, 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. |
Los objetivos secundarios de este estudio son los siguientes: - Evaluar la relación entre la dosis y exposición a JNJ-54861911 y la seguridad en pacientes con EA temprana. - Evaluar la farmacocinética a lo largo del tiempo de JNJ-54861911 en pacientes con EA temprana. - Evaluar las variaciones de especies de Aß (Aß1-37, Aß1-38, Aß1-40, Aß1-42) y de fragmentos de la proteína precursora del amiloide soluble (sAPP) (sAPP?, sAPPß, sAPP total) en líquido cefalorraquídeo (LCR) a los 6 meses de tratamiento con JNJ-54861911 en comparación con placebo en pacientes con EA temprana. - Evaluar las variaciones de Aß1-40 y fragmentos de sAPP (sAPP?, sAPP ß, sAPP total) en plasma a los 6 meses de tratamiento con JNJ-54861911 en comparación con placebo en pacientes con EA temprana. - Evaluar la relación entre las variaciones de especies de Aß y fragmentos de sAPP en LCR y plasma y la seguridad en pacientes con EA temprana. |
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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. 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. |
Para poder participar en el estudio, los candidatos deberán cumplir todos los criterios siguientes: 1. Los pacientes con EA temprana deben tener una puntuación CDR global de 0 (asintomático con riesgo de EA) a 0,5 (EAp), ambos inclusive. 2. Pacientes con EAp: el paciente debe ser de uno u otro sexo y tener una edad comprendida entre los 50 y 85 años, ambos inclusive. Pacientes asintomáticos con riesgo de EA: el paciente debe ser de uno u otro sexo y tener una edad comprendida entre los 65 y 85 años, ambos inclusive. 3. Los pacientes deben tener un nivel de estudios o una experiencia laboral suficientes para descartar un retraso mental y han de saber leer y escribir.
4. Los pacientes deben presentar indicios de patología amiloidea, a tenor de: a) concentraciones bajas de A?1-42 en LCR en la visita de selección#. b) PET amiloide positivo en la visita de selección (dependiendo de la posibilidad de realizar PET del centro) mediante interpretación visual 5. Los pacientes deben tener un índice de masa corporal (IMC = peso/estatura²) de entre 18 y 35 kg/m2, ambos inclusive, en la visita de selección. 6. Antes de la aleatorización, las mujeres no deben estar en edad fértil: deben ser posmenopáusicas (? 50 años de edad con amenorrea durante al menos 12 meses), estar esterilizadas permanentemente (por ejemplo, ligadura de trompas, histerectomía o salpingectomia bilateral) o ser incapaces de quedarse embarazadas por otro motivo. En caso de situación dudosa, deberá consultarse al personal cualificado del promotor para decidir sobre la posible inclusión de la paciente. 7. os varones que mantengan relaciones sexuales con mujeres en edad fértil y no se hayan sometido a una vasectomía deben comprometerse a utilizar un método anticonceptivo de barrera (por ejemplo, preservativo con espuma, gel, película, crema o supositorio espermicida o, en la pareja, diafragma o capuchón cervical/vaginal con espuma, gel, película, crema o supositorio espermicida), así como a no donar semen durante el estudio y hasta 3 meses después de recibir la última dosis del fármaco del estudio. Además, las parejas, en caso de estar en edad fértil, también deben utilizar un método anticonceptivo adecuado durante al menos el mismo período. Los métodos anticonceptivos eficaces comprenden anticonceptivos orales de venta con receta, anticonceptivos inyectables, dispositivos intrauterinos, métodos de doble barrera y parches anticonceptivos. 8. Los pacientes deben estar sanos, por lo demás, para su grupo de edad o médicamente estables, con o sin medicación, según la exploración física, los antecedentes médicos, las constantes vitales y el ECG de 12 derivaciones obtenidos en la visita de selección o basal. En caso de anomalías, han de ser compatibles con la enfermedad subyacente en la población del estudio y no una posible causa de deterioro cognitivo, con la conformidad por escrito del monitor médico del promotor. 9. Los pacientes deben estar sanos o médicamente estables, por lo demás, según los análisis clínicos efectuados en la visita de selección. Si los resultados de bioquímica sérica (incluidas enzimas hepáticas y otras pruebas específicas), hematología y análisis de orina se encuentran fuera del intervalo de referencia normal, el paciente únicamente podrá ser incluido si el investigador considera que las anomalías o desviaciones de la normalidad carecen de importancia clínica, resultan apropiadas y razonables para la población estudiada y no son una causa potencial de deterioro cognitivo, con la conformidad por escrito del monitor médico del promotor. Esta decisión deberá consignarse en los documentos originales del paciente con las iniciales del investigador. 10. Los pacientes deben contar con un informador fiable (familiar, pareja o amigo). El informador ha de estar dispuesto a participar como fuente de información y tener, como mínimo, un contacto semanal con el paciente (el contacto podrá ser en persona, por teléfono o por comunicación electrónica). El informador ha de tener un contacto suficiente para que el investigador considere que puede aportar información importante sobre las funciones cotidianas del paciente. 11. Los pacientes deben ser capaces de tomar la medicación de la forma prescrita. 12. Los pacientes deben ser capaces de tragar el fármaco entero. 13. Los pacientes deben ser capaces de respetar las prohibiciones y restricciones especificadas en este protocolo y estar dispuestos a hacerlo. 14. Los pacientes deben firmar un documento de consentimiento informado que indique que entienden la finalidad del estudio y los procedimientos que exige y que están dispuestos a participar en él. |
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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 or 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. 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. |
Para más información por favor consulte las páginas 22-25 del resumen en castellano del protocolo, de fecha 29 de Julio de 2014 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The assessment of specified safety parameters of JNJ-54861911 |
La evaluación de los parámetros de seguridad especificados de JNJ-54861911 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The assessment of specified pharmacokinetic parameters of JNJ-54861911 |
La evaluación de los parámetros farmacocinéticos especificadas de JNJ-54861911 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 7 |
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
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LVLS |
Última Visita Último Paciente |
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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 |