The purpose of this study is to evaluate the benefit of adding an adjuvant to CAD106 and to select the dose of CAD106 and adjuvant to be used in further development. Additionally, clinical and biomarker measures (CSF, plasma biomarkers, volumetric…
ID
Source
Brief title
Condition
- Other condition
- Neurological disorders NEC
Synonym
Health condition
Dementie van het Alzheimer type
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Frequency of adverse events, cerebral MRI scan, injection-related reactions
collected in a patient diary, vital signs, neurological and physical
examination, ECG, blood sedimentation rate, hematology, blood chemistry,
urinalysis, specific immunological safety tests in blood and CSF
Secondary outcome
Ab-specific antibody levels in serum and CSF, Ab- and Qb-specific T-cells,
MMSE, CDR, ADCS - ADL, NPI-Q, ADAS - Cog, CogState Tests, COWAT, CFT;
Volumetric MRI. Additionally, PET imaging with florbetapir F18 if participating
in PET substudy.
Background summary
Alzheimer*s disease (AD) is one of the most prevalent neurological disorders
among the elderly worldwide. Currently, the only pharmacological therapies
available are symptomatic drugs, such as cholinesterase inhibitors, and other
drugs to control the secondary behavioral symptoms of AD. Accumulating evidence
strongly suggests that the *-amyloid peptide plays a causal role in AD and that
successful strategies for a disease-modifying therapy are likely to include
products that directly or indirectly affect the deposition of *-amyloid in the
brain. Immunotherapy has emerged as a promising approach to achieve this goal.
CAD106 is such immunotherapy and the safety and immunogenicity of CAD106 need
to be further evaluated in AD patients. The current study focuses on the
assessment of the safety and tolerability of the theraphy, in combination with
an adjuvant.
Study objective
The purpose of this study is to evaluate the benefit of adding an adjuvant to
CAD106 and to select the dose of CAD106 and adjuvant to be used in further
development. Additionally, clinical and biomarker measures (CSF, plasma
biomarkers, volumetric MRI ) will be assessed to generate hypotheses to be
further studied in Phase IIb/III. PET imaging with florbetapir F18 (at
participating centers) will also support this additional objective.
Study design
This is a multi-center, randomized, double-blind, placebo-controlled study in
patients with mild AD. After a screening period of max. 5 weeks, eligible
patients will be allocated to the active drug (CAD106 +/- adjuvant) or placebo
in a 7:1 randomization ratio under double-blind conditions. Study medication
will be injected intramuscular at weeks 0, 6, 12, 24, 36, 48 and 60. Thereafter
patients will continue in the study for a total duration of 90 weeks. Frequent
safety evaluations will be performed to allow close monitoring of patients, in
particular 2 lumbar punctures, and 6 MRIs to monitor any unwanted immune
response. An independent, unblinded Data Safety Monitoring Board will review
the data from the study on an ongoing basis and will be involved in all the
major decisions during the study.
Intervention
In cohort I all patients receive 7 injections of CAD106 or placebo. There are 6
arms:
- Arm 1: Injection 1-7: CAD106 150 ug + Alum 150 ug
- Arm 2: Injection 1-3: CAD106 150 ug + Alum 50 ug, injection 4-7: CAD106 150
ug + Alum 450 ug
- Arm 3: Injection 1-7: Placebo + Alum 150 ug
- Arm 4: Injection 1-3: CAD106 150 ug + MF59 250 uL, injection 4-7: CAD106 450
ug without adjuvant
- Arm 5: Injection 1-3: CAD106 150 ug + MF59 150 uL, injection 4-7: CAD106 450
ug without adjuvant
- Arm 6: Injection 1-3: Placebo + MF59 250 uL, injection 4-7: Placebo without
adjuvant
In cohort II all patients receive 7 injections of CAD106 (with or without
adjuvant) or placebo. There are 3 arms:
- CAD106 450 ug + Alum 450 ug
- CAD106 450 ug without adjuvant
- Placebo + Alum 450 ug
Study burden and risks
The patient will visit the hospital 22 times during 90 weeks. During these
visits, the following assessments will take place: 22 x lab assessment 2 x
lumbar punction 22 x blood pressure, pulse, body temperature and weight 11 x
physical examination and neurological examination 6 x ECG 6 x cerebral MRI, 6 x
completion of different tests/scales. In case patient participates in the PET
substudy: additionally 3 x PET imaging with Florbetapir F18. The patient needs
to complete a diary for 7weeks. The blood draws, the lumbar punctions and the
intravenous injections with Florbetapir (latter is performed only in the
patients participating in the PET substudy) may cause some discomfort. These
assessments will be performed by well trained personnel with experience. For
some people MRI scan and PET imaging (latter is performed only in the patients
participating in the PET substudy) may cause some discomfort. To be able to
take part in the study, there should be a care giver/partner with the patient
that will join the patient to all study visits.
Raapopseweg 1
6824 DP Arnhem
NL
Raapopseweg 1
6824 DP Arnhem
NL
Listed location countries
Age
Inclusion criteria
- Male and female patients below the age of 85 years. For PET Substudy (amendment 3): Male and female patients equal to or above the age of 50 years and below the age of 85 years
- 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
- Patients who satisfy the criteria for a clinical diagnosis of probable AD established by NINCDS-ADRDA
- Mild AD as confirmed by a MMSE score of 20 to 26 (both inclusive)
- Primary caregiver is present and willing to assent in writing to taking the responsibility for assessing the condition of the patient throughout the study, and for providing input to safety and tolerability assessments in accordance with all protocol requirements.
Exclusion criteria
- Any medical or neurological condition, other than AD, that contributes significantly to the patient*s dementia
- History in the past two years or current diagnosis of CNS inflammation
- Evidence of vascular dementia or other cerebrovascular disease
- Current DSM-IV diagnosis of major depression and/or any other DSM-IV Axis 1 diagnosis that may interfere with the evaluation of the patient*s response to study medication
- Current diagnosis of an active, uncontrolled seizure disorder.
- History or current diagnosis of an active autoimmune disease
- Coronary heart disease
- Symptomatic heart failure
- Initiation or change in dose of current treatment with cholinesterase-inhibitors (ChEIs) and/or other AD treatment in the 4 weeks prior to clinical assessments
- History of alcohol or drug abuse within the last 2 years and/or current alcohol/drug abuse
- Patients who have been declared mentally incompetent
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-012394-35-NL |
| ClinicalTrials.gov | NCT01097096 |
| CCMO | NL30823.000.09 |