E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild Alzheimer's Disease. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
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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 safety and tolerability of repeated subcutaneous (s.c.) injections of 150µg CAD106 in patients with mild Alzheimer's Disease over the 52 weeks of the study. |
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E.2.2 | Secondary objectives of the trial |
• To determine the Aβ-specific antibody response to CAD106 by means of evaluating titer levels (IgG and IgM) in serum and in CSF; and assessing Qβ-specific antibody response: (IgG and IgM) in serum over the 52 weeks of the study. • To characterize Aβ-specific and Qβ-specific T-cell response in PBMCs from patients receiving CAD106 or placebo over the first 14 weeks of the study.
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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 |
Exploratory biomarker sub-studies on pharmacogenetics and blood pharmacogenomics are detailed in the enclosed protocol (section 7.8). These sub-studies are optional as only performed on patients who agree to participate by signing a separate informed consent.
Please see enclosed protocol, Section 7.8, for further details |
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E.3 | Principal inclusion criteria |
Key Inclusion criteria:
• Male and/or female patients between 40 and 85 years of age (both inclusive). • Female patients must be without childbearing potential (post-menopausal or surgically sterilized). • Diagnosis of dementia of the Alzheimer’s type according to the DSM-IV criteria (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) and satisfying the NINCDS-ADRA criteria for a clinical diagnosis of probable AD. • Mild AD as confirmed by MMSE score of 20 to 26 (both inclusive) at screening, untreated or on stable dose of cholinesterase inhibitor or memantine over the last 6 weeks. • With sufficient education and able to provide written informed consent prior to study participation. Having support from a primary caregiver accepting to accompany the patient at visits and assess the patient’s condition.
Please see enclosed protocol, section 5.1, for further details. |
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E.4 | Principal exclusion criteria |
Key Exclusion criteria:
• Any medical or neurological condition, other than AD, that contributes significantly to the patient’s dementia, including any CSF and/or cerebral MRI findings at screening. • History in the past two years or current diagnosis of CNS inflammation. • History or current diagnosis of significant cerebrovascular disease as defined by MRI central reader with a Hachinski score > 4. • >2 cerebral microhemorrhages or other relevant MRI findings. • History or current diagnosis of an active autoimmune disease. • Current diagnosis of a clinically relevant atopic condition. • Evidence of current inflammation or of any acute disease or infection in past 4 weeks, including fever (>38°C) in the 3 days prior to the first injection. • History of immunocompromise, or testing positive for Hepatitis B or Hepatitis C. • Vital signs outside of normal ranges for their age group • History of any severe or unstable cardiovascular disease, including QTc ≥ 450msec in males and ≥ 470msec in females. • Treatment with any of the following substances: - in the 3 months prior to first injection: • any investigational drug; any drug or treatment known to cause major organ system toxicity; - in the 6 weeks prior to first injection: • any new anticoagulants (excluding acetylsalicylic acid) or antiplatelet agents; • de novo initiation of treatment or change in dose of current treatment with cholinesterase-inhibitors (ChEIs) and/or memantine • start of treatment with psychotropic medication (with the exception of mild hypnotic drugs, and low doses of neuroleptic drugs); • centrally acting anticholinergic drugs including tricyclic and tetracyclic antidepressants or change in dose of non-anticholinergic antidepressant therapy; - in the 2 weeks before and after any of the three injections: • any other immunization • Participation in any other AD immunotherapy study receiving active treatment. • History in past 5 years or current treatment with immunosuppressive drugs, except local application of steroids.
Please see enclosed protocol, section 5.1, for further details.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to establish the safety and tolerability of repeated injections of 150µg of CAD106.
For the analysis of the primary objective, the following variables will be analysed: • Frequency of adverse events. • Frequency of cerebral MRI and CSF findings related to either inflammation, vasogenic edema or microhemorrhages. • Frequency of injection-related reactions from the patient’s diary.
Please see enclosed protocol, section 10.4, for further details.
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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 | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Determine Aβ- and Qβ-specific antibody titers in serum and in CSF (IgM and IgG). |
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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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | Information not present in EudraCT |
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 |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 14 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 14 |