E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 100000004852 |
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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 |
•To evaluate the efficacy of MABT5102A compared with placebo, when administered over 68 weeks to patients with mild to moderate AD, in inhibiting disease progression using the Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAS-Cog [12-item])
•To evaluate the safety and tolerability of MABT5102A compared with placebo when administered over 68 weeks to patients with mild to moderate AD
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of MABT5102A compared with placebo, when administered over 68 weeks to patients with mild to moderate AD, in inhibiting disease progression using a global assessment measure, the Clinical Dementia Rating, Sum of Boxes (CDR-SOB) score |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
SUBSTUDY IN ASSOCIATION WITH MABT5102A STUDY ABE4869g
Dated 10 Dec 2010
The objectives of this research substudy are to characterize the effects of MABT5102A on multiple putative neurodegenerative and pharmacodynamic measures in the CSF of AD patients and to determine whether posttreatment changes are associated with or predict clinical response to MABT5102A.
DNA REPOSITORY SUBSTUDY IN ASSOCIATION WITH MABT5102A STUDY ABE4869g
Dated 10 Dec 2010
The primary objective of this study is to perform exploratory analyses to generate hypotheses identifying genes associated with treatment response, toxicity, or disease risk. If such genetic hypotheses are identified, they may be tested in future clinical studies within this therapeutic area. |
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E.3 | Principal inclusion criteria |
General
•Ability to provide written informed consent by the patient and a legally authorized health care representative for the patient
•Ability and willingness of patient and a legally authorized health care representative to comply with the protocol’s requirements
•Age 50−80 years
•Body weight ≥ 45 kg and ≤ 120 kg
•Adequate visual and auditory acuity in the investigator's judgment to allow for neuropsychological testing
•Fluent in the language of the test assessments
•Negative urine test for drugs of abuse (including medical marijuana) at screening
•For female patients, a negative serum β–human chorionic gonadotropin (β-hCG) pregnancy test at screening
•Normal thyroid-stimulating hormone (TSH) and vitamin B12 levels at screening
•For male patients with partners with reproductive potential, agreement to use a reliable means of contraception (e.g., condoms) during the study
•Availability of a person who can provide information on activities of daily living and behavior to complete the related assessments
This person must live with the patient at least 4 days per week and be familiar with the overall function and behavior of the patient.
Related to Neurology/Cognition
•Diagnosis of probable AD according to the NINCDS-ADRDA criteria (McKhann et al. 1984)
•MMSE score of 18−26 points at screening (Folstein et al. 1975)
•GDS-15 score of < 6
•CDR score of ≥ 0.5
•Completion of 6 years of education (or good work history consistent with exclusion of mental retardation or other pervasive developmental disorders)
Related to Medication
•For patients currently receiving treatment with approved AD treatments (AChE inhibitors or memantine): Treatment initiated and continued for at least the last 3 months prior to screening, at a stable dose for at least the last 2 months prior to screening
•For patients currently receiving other prescription medications: Treatment at a stable dose for ≥ 1 month prior to screening
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E.4 | Principal exclusion criteria |
General
•Female patient with reproductive potential
Female patients must either have undergone documented surgical sterilization or have not experienced menstruation for at least 12 consecutive months.
•Severe or unstable medical condition that, in the investigator's or Sponsor's opinion, would interfere with the patient's ability to complete the study assessments or would require the equivalent of institutional or hospital care
Related to Medical History/Conditions
•History or presence of clinically evident vascular disease potentially affecting the brain (e.g., stroke, clinically significant carotid or vertebral stenosis or plaque, aortic aneurysm, intracranial aneurysm, cerebral hemorrhage, arteriovenous malformation)
•Presence of more than two micro- or macrohemorrhages as assessed by T2* weighted GRE MRI
•History of severe, clinically significant (persistent neurologic deficit or structural brain damage) central nervous system trauma (e.g., cerebral contusion)
•History or presence of intracranial tumor (e.g., meningioma, glioma)
•Presence of potential metabolic cause of dementia or encephalopathy (e.g., vitamin B12 deficiency, thyroid abnormalities)
•History or presence of infections that affect the brain (e.g., syphilis, neuroborreliosis, viral or bacterial meningitis/encephalitis, HIV encephalopathy)
•History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., multiple sclerosis, lupus erythematosus, anti-phospholipid antibody syndrome, Behçet disease)
•History or presence of psychiatric disease other than AD that may affect cognition, including but not limited to clinically significant major psychiatric disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) (e.g. major depression, schizophrenia, bipolar disorder)
•History or presence of a neurologic disease other than AD that may affect cognition, including but not limited to Parkinson’s disease, corticobasal degeneration, dementia with Lewy bodies, Creutzfeldt–Jakob disease, progressive supranuclear palsy, frontotemporal degeneration, Huntington’s disease, normal pressure hydrocephalus, and hypoxia
•Presence of visual hallucinations, parkinsonism, chorea, eye movement abnormalities, dystonia, or gait disturbance suggestive of a non-AD diagnosis
•History of seizures with the exception of childhood febrile seizures
•History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins
•Known or suspected history of alcohol or drug abuse within the previous 5 years (DSM-IV criteria) Medical marijuana is allowed if stopped 3 months prior to screening.
•Evidence of malignancies, acute infections, renal failure that requires dialysis, or other unstable medical disease
•Hospitalization within 4 weeks prior to screening
•History of atrial fibrillation
•Thyroid disease unless euthyroid on treatment
•Clinically significant laboratory or ECG abnormalities in the investigator’s judgement
•Prolonged QTc interval (> 450 msec in males, > 470 msec in females)
•Impaired renal function (creatinine > 2 times the upper limit of normal [ULN])
•Impaired hepatic function (as indicated by transaminases > 1.2 x ULN or abnormalities in synthetic function tests judged by the investigator to be clinically significant)
•Impaired coagulation (PT or PTT > 1.5 x ULN)
•Platelet count < 100,000/uL
•Evidence of poorly controlled diabetes (glycosylated hemoglobin [HbA1c] >8.0%)
•Presence of significant cerebral vascular pathology as assessed by MRI imaging
Related to Medication
•Previous treatment with MABT5102A or any other therapeutic that targets Abeta
•Treatment with any investigational agent within 4.5 half-lives or 4 weeks prior to screening, whichever is longer
•Chemotherapy-induced cognitive dysfunction
•Chronic treatment with systemic steroids
•Treatment with any biologic therapy within 5 half-lives or 3 months prior to screening, whichever is longer, with the exception of routinely recommended vaccinations, which are allowed
See Protocol for full list |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy outcome measure is change in ADAS-Cog (12-item) score between baseline and Week 73. This will be used to estimate the difference in mean change from baseline in ADAS-Cog (12-item) score at Week 73 between MABT5102A- and placebo-treated patients. Analysis of covariance (ANCOVA) adjusting for ApoE4 status and MMSE score will be used to estimate the primary endpoint. |
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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) |
Change in ADCS-ADL score from baseline to Week 73 |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | 2 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Germany |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |