Safety, Tolerability and Abeta-specific Antibody Response of Repeated i.m. Injections of Adjuvanted CAD106 in Mild Alzheimer Patients

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01097096

Collaborator

(none)

177

Enrollment

Locations

Arms

33.1

Duration (Months)

5.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will assess the safety, tolerability and Abeta-specific antibody response of repeated intra-muscular injections of adjuvanted CAD106 in patients with mild Alzheimer's Disease.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Biological: CAD106 Biological: Placebo Biological: Alum Biological: MF59	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

177 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official 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

Study Start Date :

Mar 1, 2010

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: CAD106 150μg + Adjuvant 1 at middle dose	Biological: CAD106 150μg and 450μg doses were reconstituted and administered via intramuscular injection Biological: MF59 An adjuvant (additive to increase potency) of low, middle and high doses which was mixed with reconstituted active CAD106
Active Comparator: CAD106 150μg + Adjuvant 1 at low dose	Biological: CAD106 150μg and 450μg doses were reconstituted and administered via intramuscular injection Biological: MF59 An adjuvant (additive to increase potency) of low, middle and high doses which was mixed with reconstituted active CAD106
Placebo Comparator: Placebo + Adjuvant 1 at middle dose	Biological: Placebo Identical placebo to CAD106 administered via intramuscular injection
Active Comparator: CAD106 150μg + Adjuvant 2 at middle dose	Biological: CAD106 150μg and 450μg doses were reconstituted and administered via intramuscular injection Biological: MF59 An adjuvant (additive to increase potency) of low, middle and high doses which was mixed with reconstituted active CAD106
Active Comparator: CAD106 150μg + Adjuvant 2 at low dose	Biological: CAD106 150μg and 450μg doses were reconstituted and administered via intramuscular injection Biological: MF59 An adjuvant (additive to increase potency) of low, middle and high doses which was mixed with reconstituted active CAD106
Placebo Comparator: Placebo + Adjuvant 2 at middle dose	Biological: Placebo Identical placebo to CAD106 administered via intramuscular injection
Active Comparator: CAD106 450μg + either Adjuvant 1 or 2 at middle dose	Biological: CAD106 150μg and 450μg doses were reconstituted and administered via intramuscular injection Biological: Alum An adjuvant (additive to increase potency ) of low, middle or high doses which was mixed with reconstituted active CAD106 Biological: MF59 An adjuvant (additive to increase potency) of low, middle and high doses which was mixed with reconstituted active CAD106
Active Comparator: CAD106 450μg + either Adjuvant 1 or 2 at low dose	Biological: CAD106 150μg and 450μg doses were reconstituted and administered via intramuscular injection Biological: Alum An adjuvant (additive to increase potency ) of low, middle or high doses which was mixed with reconstituted active CAD106 Biological: MF59 An adjuvant (additive to increase potency) of low, middle and high doses which was mixed with reconstituted active CAD106
Placebo Comparator: Placebo + either Adjuvant 1 or 2 at middle dose	Biological: Placebo Identical placebo to CAD106 administered via intramuscular injection

Outcome Measures

Primary Outcome Measures

Safety and tolerability assessments (physical/neurological examinations, electrocardiogram (ECG), vital signs, standard and special laboratory evaluations, Magnetic Resonance Imaging (MRIs), Adverse events / Serious adverse events (AE/SAE) monitoring). [Screening and through the end of the study to Week 90]

Secondary Outcome Measures

Amyloid beta (Aβ)-specific and Qβ carrier-specific antibody response to CAD106 (with either adjuvant) in serum and cerebrospinal fluid (CSF) [Screening and through the end of the study to Week 90]
Amyloid beta (Aβ)-specific and Qβ carrier-specific T-cell response to CAD106 (with either adjuvant) using peripheral blood mononuclear cells (PBMCs) [Screening and at week 8]
Changes over time of the concentrations of disease related markers (Aβ1-40 and Aβ1-42 in plasma; Aβ1-40, Aβ1-42, total-tau, phospho-tau in CSF, or other markers) in patients with mild AD receiving CAD106 (with either adjuvant) compared to placebo [Screening and through the end of the study to Week 90]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and/or female patients below 85 years of age (inclusive)
Diagnosis of mild Alzheimer's Disease
Mini-Mental State Examination (MMSE) 20 to 26 (inclusive) at screening, untreated or on stable dose of cholinesterase inhibitor or memantine over the last 4 weeks prior to clinical assessments

Exclusion Criteria:

Previously participated in an AD vaccine study and received active treatment
History or presence of an active autoimmune disease
History or presence of seizure disorder
Presence of significant coronary heart disease and/or cerebrovascular disease
Presence of other neurodegenerative disease and/or psychiatric disorders (with the exception of successfully treated depression)
Advanced, severe, progressive or unstable disease that might interfere with the safety, tolerability and pharmacodynamic assessments of the patient

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Costa Mesa	California	United States	92626
2	Novartis Investigative Site	Boulder	Colorado	United States	80304
3	Novartis Investigative Site	Hollywood	Florida	United States	33021
4	Novartis Investigative Site	Indianapolis	Indiana	United States	46202-5266
5	Novartis Investigative Site	Eatontown	New Jersey	United States	07724
6	Novartis Investigative Site	Antwerpen		Belgium	2020
7	Novartis Investigative Site	Leuven		Belgium	3000
8	Novartis Investigative Site	Toronto	Ontario	Canada	M3B 2S7
9	Novartis Investigative Site	Toronto	Ontario	Canada	M6M 3Z5
10	Novartis Investigative Site	Greenfield Park	Quebec	Canada	J4V 2J2
11	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 2M4
12	Novartis Investigative Site	Magdeburg		Germany	39120
13	Novartis Investigative Site	Nuernberg		Germany	90402
14	Novartis Investigative Site	Brescia	BS	Italy	25123
15	Novartis Investigative Site	Firenze	FI	Italy	50134
16	Novartis Investigative Site	Genova	GE	Italy	16132
17	Novartis Investigative Site	Milano	MI	Italy	20122
18	Novartis Investigative Site	Roma	RM	Italy	00161
19	Novartis Investigative Site	Roma	RM	Italy	00179
20	Novartis Investigative Site	Amsterdam		Netherlands	1081 GM
21	Novartis Investigative Site	Stavanger		Norway	4068
22	Novartis Investigative Site	Sant Cugat	Barcelona	Spain	08190
23	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
24	Novartis Investigative Site	Barcelona	Cataluña	Spain	08003
25	Novartis Investigative Site	Barcelona	Cataluña	Spain	08041
26	Novartis Investigative Site	Barakaldo	País Vasco	Spain	48903
27	Novartis Investigative Site	Mölndal		Sweden	43141
28	Novartis Investigative Site	Stockholm		Sweden	SE-141 86
29	Novartis Investigative Site	Basel		Switzerland	4031
30	Novartis Investigative Site	Biel		Switzerland	2500
31	Novartis Investigative Site	Lausanne		Switzerland	1011