E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alzheimer's Disease |
Alzheimer-Krankheit |
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E.1.1.1 | Medical condition in easily understood language |
Alzheimer's Disease |
Alzheimer-Krankheit |
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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 | 16.1 |
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 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). |
- Untersuchung der langfristigen Sicherheit und Verträglichkeit der
fortlaufenden Verabreichung von AFFITOP®AD02 nach einem
vordefinierten Impfschema (nach der ersten Impfung [„Grundimmunisierung"] folgen in regelmäßigen Abständen
Auffrischungsimpfungen [„booster"]) über einen Gesamtzeitraum von 37 Monaten (beinhaltet den Zeitraum der vorhergehenden AFF006- Studie über 18 Monate).
- Untersuchung der klinischen Wirksamkeit (kognitive und funktionale Parameter) der Vakzinierung mit AFFITOP®AD02 bei Extension des Vakzinationsschemas (das in der vorhergehenden Phase-II-Studie AFF006 angewendet wurde) durch Verabreichung von Auffrischungsimpfungen in regelmäßigen Abständen (Vergleich mit vorhergehenden Placebo-Patienten, die jetzt mit Verum geimpft werden). |
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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). |
Untersuchung der immunologischen und klinischen Wirksamkeit (kognitive und funktionale Parameter sowie Parameter für allgemeine Aspekte, Verhalten, Lebensqualität) der Impfung mit AFFITOP®AD02 bei Extension des Vakzinationsschemas, das in der vorhergehenden Phase-II-Studie AFF006 angewendet wurde (Vergleich mit vorhergehenden Placebo-Patienten, die jetzt mit dem Verum geimpft werden). |
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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 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. |
1. Teilnahme an der AFF006 mit Erhalt von 6 Injektionen mit dem Prüfmedikament und Absolvierung aller Besuche, falls nicht vom Sponsor bestätigt
2. Vom Patienten und seinem Betreuer unterschriebene und datierte Einwilligungserklärung. Die Fähigkeit des Patienten zur Abgabe einer Einwilligungserklärung muss von einem unabhängigen Experten (Psychiater, Neurologe oder Psychologe, je nach den Bestimmungen des entsprechenden Landes) bestätigt werden.
3. Verfügbarkeit eines (Ehe)-Partners /Betreuers, der den Patienten kennt und ihn zu den Besuchen begleiten kann und für die Telefon-Interviews (TIs) zur Verfügung steht. Dies ist notwendig, weil für einige neuropsychiatrische Tests Auskünfte von einer Person erforderlich sind, die den Patienten gut kennt. Weiterhin wird dadurch die Sicherheit für den Studienteilnehmer erhöht.
4. Weibliche Patienten im gebärfähigen Alter sind geeignet, wenn sie eine bewährte Kontrazeptionsmethode anwenden.
5. Ein geplanter, elektiver Krankenhausaufenthalt für diagnostische Abklärung ist erlaubt, um in die klinische Studie aufgenommen zu werden.
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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.
12. Institutionalized patients.
13. Patients having shown a treatment-related SAE or a SUSAR in AFF006 are to be excluded from the study. |
1. Schwangerschaft.
2. Sexuelle Aktivität bei Frauen im gebärfähigen Alter, die keine medizinisch anerkannte Verhütungsmethode anwenden, und unzuverlässige Kontrazeption bei männlichen Teilnehmern.
3. Teilnahme an der aktiven Behandlungsphase einer anderen klinischen Studie außer AFF006 innerhalb von 3 Monaten vor Besuch 0.
4. Vorgeschichte einer zweifelhaften Einhaltung des Zeitplans der Studienbesuche; Patient wird klinische Studie voraussichtlich nicht beenden.
5. Allergie gegen Bestandteile des Impfstoffes in der Vorgeschichte, falls vom Prüfarzt als relevant eingestuft.
6. Kontraindikationen für MRT-Aufnahmen sind unter anderem: Herzschrittmacher; Cochlea-Implantate, zerebrale Aneurysmaclips; implantierte Infusionspumpen; implantierte Nervenstimulatoren; Metallsplitter im Auge; oder eine andere beliebige klinische Vorgeschichte oder klinische Befunde, die nach Einschätzung des Prüfarztes eine potenzielle Gefahr im Zusammenhang mit MRT darstellen würden. Auf Grundlage der Anzahl von MH bei Baseline der AFF006 und ihrer Anzahl bei den MRT-Aufnahmen während der Nachbeobachtung können Ausnahmen gemacht werden. Entscheidung nach Absprache mit dem Sponsor.
7. Vorliegen und/oder Vorgeschichte einer Immundefizienz (z. B. HIV-Infektion).
8. Vorhergehende und/oder aktuelle Behandlung mit experimentellen Immuntherapeutika, einschließlich IVIG, Antikörpertherapie gegen AD und/oder Impfstoffe gegen AD außer AD02.
9. Vorhergehende und/oder aktuelle Behandlung mit Immunsuppressiva.
10. Behandlung mit Benzodiazepinen und/oder Nootropika in hohen Dosen und/oder als Neubehandlung.
11. Behandlung mit Anticholinergika, einschließlich Parkinson-Behandlungen, (trizyklischen) Antidepressiva, Neuroleptika mit anticholinergen Eigenschaften, bestimmten Blasen-Relaxantien, Anticholinergika zur Anwendung bei Lungenkrankheiten.
12. Personen, die auf behördlicher oder gerichtlicher Anordnung in einer Anstalt untergebracht wurden.
13. Patienten der Aff006, die im Zusammenhang mit der Behandlung ein SAE oder eine SUSAR erfahren haben. |
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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 | 8 |
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 |