PMID- 29231230
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 2426-0266 (Electronic)
IS  - 2274-5807 (Linking)
VI  - 2
IP  - 2
DP  - 2015
TI  - Results from a Phase II Study to Assess the Clinical and Immunological Activity 
      of AFFITOPE(R) AD02 in Patients with Early Alzheimer's Disease.
PG  - 103-114
LID - 10.14283/jpad.2015.63 [doi]
AB  - OBJECTIVES: The primary objective of this clinical trial was to assess the 
      clinical activity of various doses and formulations of AFFITOPE(R) AD02 following 
      its repeated s.c. administration to patients with early Alzheimer s disease (AD), 
      based on the evaluation of cognitive and functional domains. DESIGN: It was 
      designed as a randomized, placebo-controlled, parallel group, double blind, 
      multicenter phase II trial with 10 regular outpatient visits and 6 telephone 
      interviews. SETTING: The trial was performed at 32 sites in six countries. 
      PARTICIPANTS: A total of 332 patients were enrolled and 265 patients completed 
      the trial in 3 treatment groups with AD02 and 2 control groups with aluminum 
      oxihydroxide, here named IMM-AD04. Patients were randomly assigned to 5 groups: 
      two doses of IMM-AD04, 25microg AD02 (in two different formulations) and 75microg AD02. 
      INTERVENTION: At months 0, 1, 2, 3, 9 and 15, each patient received a single s.c. 
      injection of the corresponding preparations of AFFITOPE(R) AD02 or the control, 
      IMM-AD04. MEASUREMENTS: Co-primary efficacy outcomes included a measure of 
      cognition (adapted AD Assessment Scale cognitive [aADAS cog]), and a measure of 
      function (adapted AD Cooperative Trial Activities of Daily Living [aADCS-ADL]). A 
      primary composite score was the sum of these two scores. RESULTS: Treatments were 
      generally well tolerated and adverse events (AEs) were seen at similar rates 
      across all treatment groups, with the exception that more injection site 
      reactions were seen in the groups with a higher level of adjuvant. None of the 
      AD02 groups showed a benefit over the IMM-AD04 controls for primary or 
      exploratory efficacy outcomes. The control groups differed on aADCS-ADL and 
      therefore couldn't be pooled (p=0.039). Unexpectedly, the 2mg IMM-AD04 showed 
      statistically significant effects over the other groups on several clinical 
      outcomes including: aADAS-cog, aADL, Composite, ADAS-cog, CDR-sb, and QOL-AD 
      Caregiver as well as two biomarker outcomes: right and total hippocampal volume 
      (all p<0.05). 48% of patients in the IMM-AD04 2mg group had no decline in the 
      composite outcome over 18 months compared to 17%-31% in the other groups, which 
      is consistent with historical placebo groups. CONCLUSION: No significant 
      treatment effects were seen for the investigational compound AD02. However, the 
      IMM-AD04 2mg group showed statistically significant effects over all other groups 
      on several clinical outcomes as well as a slowing of decline on right hippocampal 
      volume. The data support further development of IMM-AD04 as a disease modifying 
      agent in line with EMA/FDA definitions.
FAU - Schneeberger, A
AU  - Schneeberger A
AD  - Achim Schneeberger, AFFiRiS AG, Karl-Farkas-Gasse 22, 1030 Wien, Austria, Email: 
      Achim.Schneeberger@affiris.com, Tel: +43-(1)-7981575-300, Fax 
      +43-(1)-7981575-311.
FAU - Hendrix, S
AU  - Hendrix S
FAU - Mandler, M
AU  - Mandler M
FAU - Ellison, N
AU  - Ellison N
FAU - Burger, V
AU  - Burger V
FAU - Brunner, M
AU  - Brunner M
FAU - Frolich, L
AU  - Frolich L
FAU - Mimica, N
AU  - Mimica N
FAU - Hort, J
AU  - Hort J
FAU - Rainer, M
AU  - Rainer M
FAU - Imarhiagbe, D
AU  - Imarhiagbe D
FAU - Kurz, A
AU  - Kurz A
FAU - Peters, O
AU  - Peters O
FAU - Gertz, H-J
AU  - Gertz HJ
FAU - Tierney, L
AU  - Tierney L
FAU - Mattner, F
AU  - Mattner F
FAU - Schmidt, W
AU  - Schmidt W
FAU - Dubois, B
AU  - Dubois B
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - J Prev Alzheimers Dis
JT  - The journal of prevention of Alzheimer's disease
JID - 101638820
OTO - NOTNLM
OT  - AFFITOPE(R)
OT  - Aluminum
OT  - Alzheimer s disease
OT  - clinical trial
OT  - vaccination
COIS- AS, MM, VB, LT, FM, WS are employees of AFFiRiS, the company that commercializes 
      the AFFITOPE(R) technology described in the manuscript. SH and NE are consultants 
      for AFFiRiS through Pentara Corporation.MB, LF, NM, JH, MR, DI, AK, OP, HG, BD 
      declare no conflict of interest.
EDAT- 2015/01/01 00:00
MHDA- 2015/01/01 00:01
CRDT- 2017/12/13 06:00
PHST- 2017/12/13 06:00 [entrez]
PHST- 2015/01/01 00:00 [pubmed]
PHST- 2015/01/01 00:01 [medline]
AID - 10.14283/jpad.2015.63 [doi]
PST - ppublish
SO  - J Prev Alzheimers Dis. 2015;2(2):103-114. doi: 10.14283/jpad.2015.63.