E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alzheimer's Disease |
Alzheimerova choroba |
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E.1.1.1 | Medical condition in easily understood language |
Alzheimer's Disease |
Alzheimerova choroba |
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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 | 16.0 |
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 assess the longterm safety and tolerability of continued AFFITOPE® AD02 administrations following a predefined vaccination schedule (boosts at regular intervals after priming) over a total period of 37 months (includes the 18 months of the preceding AFF006 study). - to assess the clinical activity (parameters for cognition and function) of vaccination with AFFITOPE® AD02 when extending the vaccination schedule applied within the preceding phase II study AFF006 by boosts at regular intervals (comparison to previous placebo patients now being vaccinated with verum). |
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E.2.2 | Secondary objectives of the trial |
To assess the immunological and clinical activity (parameters for cognition, function, global aspects, behavior, quality of life) of vaccination with AFFITOPE® AD02 when extending the vaccination schedule applied within the preceding phase II study AFF006 (comparison to previous placebo patients now being vaccinated with verum). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients having participated in AFF006 as well as having received 6 IMP injections and having completed all visits, if not approved by the sponsor.
2. Written informed consent signed and dated by the patient (or her/his legal representative) and the caregiver. The patient’s capability to give informed consent has to be confirmed by an independent professional (psychiatrist, neurologist or psychologist dependent on the regulations in a given country).
3. Availability of a partner/caregiver knowing the patient and being able to accompany the patient at the visits and being available for the telephone interviews.
4. Female patients of childbearing potential are eligible if they use a medically accepted contraceptive method.
5. Scheduled elective hospitalization for diagnostic work-up is allowed for inclusion into the clinical trial. |
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E.4 | Principal exclusion criteria |
1. Pregnant women.
2. Sexually active women of childbearing potential who are not using a medically accepted birth control method and unreliable contraception in male subjects.
3. Participation in the active treatment phase of another clinical trial except AFF006 within 3 months before Visit 0.
4. History of questionable compliance to visit schedule; patients not expected to complete the clinical trial.
5. Presence or history of allergy to components of the vaccine, if considered relevant by the investigator.
6. Contraindication for Magnetic Resonance Imaging (MRI) imaging, including but not limited to pacemakers; cochlear implants, cerebral aneurysm clips; implanted infusion pumps; implanted nerve stimulators; metallic splinters in the eye; other magnetic, electronic, or mechanical implants; or any other clinical history or examination finding that, in the judgement of the investigator, would pose a potential hazard in combination with MRI. Exceptions may apply based on the number of Microhemorrhages (MHs) at baseline of AFF006 and their number over the follow-up MRIs. To be decided after consultaion with the sponsor.
7. Presence and/or history of Immunodeficiency (e.g., HIV infection).
8. Prior and/or current treatment with experimental immunotherapeutics including Intravenous Immunoglobulin (IVIG), Alzheimer’s Disease (AD) antibody therapy and/or vaccines for AD except AD02.
9. Prior and/or current treatment with immunosuppressive drugs.
10. Treatment with benzodiazepines and/or nootropics administered at high doses and/or as newly started treatment.
11. Treatment with anticholinergic drugs including Parkinson treatments, antidepressants (tricyclics), neuroleptics with anticholinergic properties, certain bladder relaxants, anticholinergic drugs for use in lung diseases. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Withdrawal criteria (number of patients who withdraw due to AEs, reason for withdrawal) - Adverse events (AEs) - Occurrence of any serious adverse events (SAE) possibly, probably or definitely related to the study vaccine at any time during the study. - Occurrence of local AEs (injection site pain, erythema (redness), hyperthermia at injection site, itching, edema (swelling), induration [hardening], granuloma within 1 week (Day 1-7) after each vaccination: Severity and duration - Occurrence of systemic AEs: headache, myalgia (muscle pain), fever, fatigue, nausea within 1 week (Day 1-7) after each vaccination: Severity and duration. - Physical and neurological examination results - Vital signs (blood pressure, heart rate, body weight) - Laboratory assessment (haematology, biochemistry, coagulation, and urinalysis)
Magnetic Resonance Imaging (MRI) of the brain to assess for events associated with AD/Aβ targeting drugs (e.g., vasogenic edema, microhemorrhages)
Co-primary efficacy endpoints: - Alzheimer Disease Assessment Scale-cognitive (ADAScog. (mod.) [cognition]) - Alzheimer' Disease Cooperative Study-Activities of Daily Living(ADCS-ADL [function]) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at any time: - Withdrawal criteria - AEs - Occurrence of any SAE possibly, probably or definitely related to the study vaccine - Physical and neurological examination results - Vital signs (blood pressure, heart rate, body weight) - Laboratory assessment (haematology, biochemistry, coagulation, urinalysis)
at V5, V7, Early Discontinuation Visit (EDV): MRI of the brain to assess for events associated with AD/Aβ targeting drugs (e.g. vasogenic edema, microhemorrhages)
within 1 week after each vaccination: - Occurrence of local AEs: injection site pain, erythema, hyperthermia at injection site, itching, edema, induration, granuloma - Occurrence of systemic AEs: headache, myalgia, fever, fatigue, nausea
at V0, V4, V5, V6, V7, EDV: - ADAScog. - ADCS-ADL |
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E.5.2 | Secondary end point(s) |
Clinical Dementia Rating 'sum of boxes' (CDR-sb) Free and Cued Selective Reminding Test (FCSRT) Standard neuropsychological test battery (CogState) Mini Mental State Examination (MMSE) Investigator’s global evaluation scale (IGE scale) Clinical Dementia Rating (CDR) [global aspects] Neuropsychiatric Inventory (NPI) [behavior] Quality of Life – in Patients with Alzheimer’s Disease (QOL-AD) Immunological parameters: Titres of IgG Abs specific for vaccine components (e.g. the immunizing peptide, monomeric Aβ and KLH) as assessed by ELISA |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at V0, V4, V5, V6, V7, EDV: Clinical Dementia Rating 'sum of boxes' (CDR-sb) Free and Cued Selective Reminding Test (FCSRT) Standard neuropsychological test battery (CogState) Mini Mental State Examination (MMSE) Clinical Dementia Rating (CDR) [global aspects] Neuropsychiatric Inventory (NPI) [behavior]
at V7, EDV: Investigator’s global evaluation scale (IGE scale)
at V0, V7, EDV: Quality of Life – in Patients with Alzheimer’s Disease (QOL-AD)
at V1, V4b, V5b, V6b, V7, EDV: Immunological parameters |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 |
Austria |
Croatia |
Czech Republic |
France |
Germany |
Slovakia |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |