A 90-week, multi-center, randomized, double-blind, placebo-controlled study in patients with mild Alzheimer’s Disease (AD) to investigate the safety, tolerability and Abeta-specific antibody response following repeated i.m. injections of adjuvanted CAD106.

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2009-012394-35-BE
• Date of registration: 03/02/2010
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A 90-week, multi-center, randomized, double-blind, placebo-controlled study in patients with mild Alzheimer’s Disease (AD) to investigate the safety, tolerability and Abeta-specific antibody response following repeated i.m. injections of adjuvanted CAD106.
• Scientific title: A 90-week, multi-center, randomized, double-blind, placebo-controlled study in patients with mild Alzheimer’s Disease (AD) to investigate the safety, tolerability and Abeta-specific antibody response following repeated i.m. injections of adjuvanted CAD106.
• Date of first enrolment: 22/03/2010
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012394-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Germany, Italy, Netherlands, Spain, Sweden, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent obtained before any assessment is performed according to local requirements for obtaining consent in mild AD patients. For PET sub-study in addition: Written informed consent to participate in the sub-study.
2. Male and female patients below the age of 85 years. For PET sub-study in addition: Patients must be 50 years of age or above to participate in the sub-study.
3. Female patients must be without childbearing potential (post-menopausal or surgically sterilized).
4. Diagnosis of dementia of the Alzheimer’s type according to the DSM-IV criteria.
5. Patients who satisfy the criteria for a clinical diagnosis of probable AD.
6. Mild AD as confirmed by a MMSE score of 20 to 26 (both inclusive) at screening, and either untreated or on stable dose of cholinesterase inhibitor and/or other AD treatment over the last 4 weeks prior to the clinical assessments.
7. Sufficient education to have been able to read, write, and communicate effectively during the pre-morbid state.
8. Cooperative, willing to complete all aspects and attend all visits of the study including lumbar puncture/CSF samplings (primarily for safety reasons), and capable of doing so, either alone or with the aid of a responsible caregiver.
9. Residing with someone in the community throughout the study or, if living alone, who have daily contact with a primary caregiver.
10. 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.

For a detailed description of the Inclusion Criteria, please refer to Section 4.1 of the enclosed protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Exclusion criteria related to CNS:
1. Any medical or neurological condition, other than AD, that contributes significantly to the patient’s dementia, including any CSF and/or brain MRI findings at screening.
2. History in the past two years or current diagnosis of CNS inflammation.
3. Evidence of vascular dementia or other cerebrovascular disease, assessed by investigator and/or MRI central reader.
4. 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, including other primary neurodegenerative dementia, schizophrenia, or bipolar disorder.
5. History or current diagnosis of seizure disorder.

Exclusion criteria related to other medical conditions:
6. Any advanced, severe, progressive, or unstable disease that may interfere with the safety, tolerability and pharmacodynamic assessments and/or with the antibody titer response in the study or put the patient at special risk
7. History or current diagnosis of an active autoimmune disease.
8. Evidence of systemic inflammation.
9. Coronary heart disease.
10. Symptomatic heart failure fulfilling the criteria of New York Heart Association (NYHA) Category > II or known left ventricular dysfunction with left ventricular ejection fraction <45%, or any other severe or unstable cardiovascular disease.
11. Vital signs outside of the following ranges at screening and baseline evaluations.
12. A QTc value greater or equal to 500 msec on the screening electrocardiogram as assessed by the central ECG reader using either Bazett or Fredericia formula, whichever the highest.
13. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases.

Exclusion criteria related to PET sub-study
25.Contraindication to PET scan investigations.
26.Participation in PET or Nuclear Medicine investigations in the previous year. 27.Intolerance to previous PET scans; i.e. previous hypersensitivity reactions to any PET ligand or imaging agent or failure to participate in and comply with previous PET scans

For a detailed description of the Exclusion Criteria, please refer to Section 4.2 of the enclosed protocol.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Alzheimer's Disease.
MedDRA version: 14.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: CAD106
Product Code: CAD106A
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Not available yet
CAS Number: N/A
Current Sponsor code: CAD106A
Other descriptive name: CAD106
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Product Name: Florbetapir F18
Product Code: 18F-AV-45
Pharmaceutical Form: Injection
INN or Proposed INN: Florbetapir F18
CAS Number: 956103-76-7
Current Sponsor code: 18F-AV-45
Other descriptive name: (E)-4-(2-(6-(2-(2-(2-[18F]fluoroethoxy)ethoxy)ethoxy)pyridin
Concentration unit: MBq megabecquerel(s)
Concentration type: equal
Concentration number: 260-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 22 visits post baseline over 90 weeks (details see protocol table 6-1)

Secondary Objective: • To characterize the Aß- and Qß-specific antibody response to CAD106 (with Alum or MF59) in serum and CSF, e.g. by measuring Aß-specific IgMs and Qß-specific IgGs in serum, and markers of the quality of the immune response.
• To characterize Aß-specific and Qß-specific T-cell response to CAD106 (with Alum or MF59) using PBMCs.
• To evaluate changes over time of the concentrations of disease related markers (Aß1-40 and Aß1-42 in plasma; Aß1-40, Aß1-42, total-tau, phospho-tau in CSF, or other markers) in patients with mild AD receiving CAD106 (with Alum or MF59) compared to placebo.

Primary end point(s): •Adverse events, serious adverse events, discontinuation due to an AE •Cerebral safety MRI (including signs of inflammation, microhemorrhages, and other findings)
•CSF findings related to inflammation (white blood cells, IgG index, oligoclonal bands in blood and CSF)
•All other safety assessments (eg. laboratory tests, ECGs, vital signs) •Injection-related reactions from the adverse events and the patient’s diary such as Bruising (Ecchymosis), Redness, Induration, Swelling, Local pain, Chills, Malaise, Muscle pain (Myalgia), Joint pain (Arthralgia), Headache, Sweating, and Fatigue
•Immune response after repeated up to 7 injections of CAD106 in each treatment arm as measured primarily by the profile of Abeta-specific IgG titers in serum. The immune response will be assessed by CMAX, TMAX, and AUC (area under the curve) and by responders status

Main Objective: • To assess the safety and tolerability of up to 7 repeated injections of CAD106 with Alum or MF59 in patients with mild Alzheimer’s Disease (AD) over 90 weeks.
• To compare the immunogenicity of CAD106 with Alum or MF59 in patients with mild Alzheimer’s Disease (AD) as measured by the titers of Aß-specific IgG in serum across regimens and in reference to non-adjuvanted CAD106.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 22 visits post baseline over 90 weeks (details see protocol table 6-1).

Secondary end point(s): As listed in protocol section 9.5

Secondary ID(s)

CCAD106A2203

2009-012394-35-NL

Source(s) of Monetary Support

Novartis Pharma Services AG