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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2016

Open Access 01-12-2016 | Research

Safety and tolerability of BAN2401 - a clinical study in Alzheimer’s disease with a protofibril selective Aβ antibody

Authors: Veronika Logovinsky, Andrew Satlin, Robert Lai, Chad Swanson, June Kaplow, Gunilla Osswald, Hans Basun, Lars Lannfelt

Published in: Alzheimer's Research & Therapy | Issue 1/2016

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Abstract

Background

Several monoclonal antibodies for the treatment of Alzheimer’s disease (AD) have been in development over the last decade. BAN2401 is a monoclonal antibody that selectively binds soluble amyloid β (Aβ) protofibrils.

Methods

Here we describe the first clinical study with BAN2401. Safety and tolerability were investigated in mild to moderate AD. A study design was used with staggered parallel single and multiple ascending doses, from 0.1 mg/kg as a single dose to 10 mg/kg biweekly for four months. The presence of amyloid related imaging abnormalities (ARIA, E for edema, H for hemorrhage) was assessed with magnetic resonance imaging (MRI). Cerebrospinal fluid (CSF) and plasma samples were analyzed to investigate pharmacokinetics (PK) and effects on biomarkers.

Results

The incidence of ARIA-E/H on MRI was comparable to that of placebo. BAN2401 exposure was approximately dose proportional, with a serum terminal elimination half-life of ~7 days. Only a slight increase of plasma Aβ(1-40) was observed but there were no measurable effects of BAN2401 on CSF biomarkers. On the basis of these findings Phase 2b efficacy study has been initiated in early AD.

Conclusions

BAN2401 was well-tolerated across all doses. The PK profile has guided us for selecting dose and dose regimens in the ongoing phase 2b study. There was no clear guidance for an effective dose based on biomarkers.

Trial registration number

NCT01230853 ClinicalTrials.gov Registered October 27, 2010.
Appendix
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Literature
1.
Ahmed M, Davis J, Aucoin D, Sato T, Ahuja S, et al. Structural conversion of neurotoxic amyloid-[beta]1-42 oligomers to fibrils. Nature Struct Mol Biol. 2010;17:561–7.CrossRef
2.
Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, Raman R, Sun X, Aisen PS, Siemers E, Liu-Seifert H, Mohs R. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s Disease. N Engl J Med. 2014;370:311–21.
3.
Englund H, Sehlin D, Johansson AS, Nilsson LN, Gellerfors P, Paulie S, Lannfelt L, Pettersson FE. Sensitive ELISA detection of amyloid-beta protofibrils in biological samples. J Neurochem. 2007;103:334–45.
4.
5.
Lacor PN, Buniel MC, Chang L, Fernandez SJ, Gong Y, Viola KL, Lambert MP, Velasco PT, Bigio EH, Finch CE, Krafft GA, Klein WL. Synaptic targeting by Alzheimer’s-related amyloid oligomers. J Neuroscience. 2004;24:10191–200.
6.
Lord A, Gumucio A, Englund H, Sehlin D, Sundquist VS, Söderberg L, Möller C, Gellerfors P, Lannfelt L, Pettersson FE, Nilsson LN. An amyloid-beta protofibril-selective antibody prevents amyloid formation in a mouse model of Alzheimer’s disease. Neurobiol Dis. 2009;36:425–34.
7.
8.
Mastrangelo IA, Ahmed M, Sato T, Liu W, Wang C, Hough P, Smith SO. High-resolution atomic force microscopy of soluble Abeta42 oligomers. J Mol Biol. 2006;358:106–19.
9.
Nilsberth C, Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K, Forsell C, Luthman J, Teplow DB, Younkin, SG, Näslund J, Lannfelt L. The ‘Arctic’ APP mutation (E693G) causes Alzheimer’s disease by enhanced Abeta protofibril formation. Nat Neurosci. 2001;4:887–93.
10.
O’Nuallain B, Freir DB, Nicoll AJ, Risse E, Ferguson N, Herron CE, Collinge J, Walsh DM. Amyloid β-protein dimers rapidly form stable synaptotoxic protofibrils. J Neurosci. 2010;30:14411–9.
11.
Paravastua AK, Leapmanb RD, Yaua WM, Tycko R. Molecular structural basis for polymorphism in Alzheimer’s amyloid fibrils. Proc Natl Acad Sci U S A. 2008;105:18349–54.CrossRef
12.
Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, Reichert M, Ketter N, Nejadnik B, Guenzler V, Miloslavsky M, Wang D, Lu Y, Lull J, Tudor IC, Liu E, Grundman M, Yuen E, Black R, Brashear HR. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s Disease. N Engl J Med. 2014;370:322–33.
13.
Schöll M, Wall A, Thordardottir S, Ferreira D, Bogdanovic N, Långström B, Almkvist O, Graff C, Nordberg A. Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers. Neurology. 2012;79:229–36.
14.
Sehlin D, Englund H, Simu B, Karlsson M, Ingelsson M, Nikolajeff F, Lannfelt L, Ekholm Pettersson F. Large aggregates are the major soluble Aβ species in AD brain fractionated with density gradient ultracentrifugation. PLoS One. 2012;7:e32014.
15.
Sehlin D, Hedlund M, Lord A, Englund H, Gellerfors P, Paulie S, Lannfelt L, Pettersson FE. Heavy-chain complementarity-determining regions determine conformation selectivity of anti-Aβ antibodies. Neurodegener Dis. 2011;8:117–23.
16.
Sperling RA, Jack CR, Black SE, Frosch MP, Greenberg SM, Hyman BT, Scheltens P, Carrillo MC, Thies W, Bednar MM, Black RS, Brashear HR, Grundman M, Siemers ER, Feldman HH, Schindler RJ. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimers Dement. 2011;7:367–85.
17.
Tucker S, Möller C, Tegerstedt K, Lord A, Laudon H, Sjödahl J, Söderberg L, Spens E, Sahlin C, Waara ER, Satlin A, Gellerfors P, Osswald G, Lannfelt L. The murine version of BAN2401 (mAb158) selectively reduces amyloid-β protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice. J Alzheimers Dis. 2015;43:575–88.
18.
19.
Walsh DM, Hartley DM, Kusumoto Y, Fezoui Y, Condron MM, Lomakin A, Benedek GB, Selkoe DJ, Teplow DB. Amyloid beta-protein fibrillogenesis. Structure and biological activity of protofibrillar intermediates. J Biol Chem. 1999;274:25945–52.
20.
Walsh DM, Lomakin A, Benedek GB, Condron MM, Teplow DB. Amyloid β-protein fibrillogenesis. J Biol Chem. 1997;272:22364–72.CrossRefPubMed
21.
Walsh DM, Selkoe DJ. Deciphering the molecular basis of memory failure in Alzheimer’s disease. Neuron. 2004;44:181–93.CrossRefPubMed
22.
Metadata
Title
Safety and tolerability of BAN2401 - a clinical study in Alzheimer’s disease with a protofibril selective Aβ antibody
Authors
Veronika Logovinsky
Andrew Satlin
Robert Lai
Chad Swanson
June Kaplow
Gunilla Osswald
Hans Basun
Lars Lannfelt
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2016
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-016-0181-2

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