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Clinical Trial
. 2021;11(3):1079-1089.
doi: 10.3233/JPD-212594.

Safety and Tolerability of Active Immunotherapy Targeting α-Synuclein with PD03A in Patients with Early Parkinson's Disease: A Randomized, Placebo-Controlled, Phase 1 Study

Werner Poewe  1 , Dieter Volc  2 , Klaus Seppi  1 , Rossella Medori  3 , Petra Lührs  3 , Alexandra Kutzelnigg  3 , Atbin Djamshidian  1 , Caroline Thun-Hohenstein  2 , Wassilios G Meissner  4 , Olivier Rascol  5 , Achim Schneeberger  3   6 , Günther Staffler  3 ; AFF011 investigators; AFF011 study investigators:; Werner Poewe  1 , Klaus Seppi  1 , Atbin Djamshidian  1 , Roberto deMarzi  1 , Beatrice Heim  1 , Stephanie Mangesius  1 , Raphaela Stolz  1 , Katarzyna Wachowicz  1 , Dieter Volc  2 , Caroline Thun-Hohenstein  2 , Constanze Riha  2 , Achim Schneeberger  3 , Vera Bürger  3 , Gergana Galabova  3
Affiliations
Clinical Trial

Safety and Tolerability of Active Immunotherapy Targeting α-Synuclein with PD03A in Patients with Early Parkinson's Disease: A Randomized, Placebo-Controlled, Phase 1 Study

Werner Poewe et al. J Parkinsons Dis. 2021.

Abstract

Background: Immunotherapies targeting α-synuclein aim to limit its extracellular spread in the brain and prevent progression of pathology in Parkinson's disease (PD). PD03A is a specific active immunotherapy (SAIT) involving immunization with a short peptide formulation.

Objective: This phase 1 study characterized the safety and tolerability of PD03A in patients with early PD. A key secondary objective was to evaluate immunological activity following immunization.

Methods: This was a phase 1 study of two different doses of PD03A versus placebo in PD patients. Patients were randomized (1:1:1) to receive four priming plus one booster vaccination of PD03A 15μg, PD03A 75μg or placebo and were followed for 52 weeks.

Results: Overall, 36 patients were randomized, of which 35 received five immunizations and completed the study. All patients experienced at least one adverse event. Transient local injection site reactions affected all but two patients; otherwise most AEs were considered unrelated to study treatment. A substantial IgG antibody response against PD03 was observed with a maximum titer achieved at Week-12. Differences in titers between both active groups versus placebo were statistically significant from the second immunization at Week-8 until Week-52.

Conclusion: The safety profile and positive antibody response of PD03A supports the further development of active immunotherapeutic approaches for the treatment of PD.

Keywords: Parkinson’s disease; active immunotherapy; immunization; α-synuclein.

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Conflict of interest statement

This study was part of an EU funded program (FP7, SYMPATH Consortium). Werner Poewe was an investigator in the study and reports receiving personal fees from AFFiRiS. Dieter Volc and Caroline Thun-Hohenstein were investigators in the study and have received funding from AFFiRiS AG. Rossella Medori has received consultancy fees from AFFiRiS; Petra Lührs and Alexandra Kutzelnigg are employed by AFFiRiS AG and Achim Schneeberger was employed by AFFiRiS AG at the time of study. Klaus Seppi and Atbin Djamshidian were investigators in the study. Wassilios Meissner and Olivier Rascol were advisors to the study as part of the SYMPATH Consortium.

Werner Poewe reports receiving personal fees from AFFiRiS, AbbVie, AstraZeneca, BIAL, Boston Scientific, Britannia, Intec, Ipsen, Lundbeck, NeuroDerm, Neurocrine, Denali Pharmaceuticals, Novartis, Orion Pharma, Prexton, Teva, UCB and Zambon. He receives royalties from Thieme, Wiley Blackwell, Oxford University Press and Cambridge University Press and grant support from the Michael J Fox Foundation, EU FP7 and Horizon 2020. Dieter Volc and Caroline Thun-Hohenstein were investigators in the study and received funding from AFFiRiS AG. Klaus Seppi reports personal fees from Teva, UCB, Lundbeck, AOP Orphan Pharmaceuticals AG, Roche, Grünenthal, Stada, Licher Pharma, Biogen and Abbvie, honoraria from the International Parkinson and Movement Disorders Society, research grants from FWF Austrian Science Fund, Michael J. Fox Foundation, and AOP Orphan Pharmaceuticals AG, outside the submitted work. Rossella Medori has received consultancy fees from AFFiRiS. Petra Lührs, Alexandra Kutzelnigg, Achim Schneeberger and Günther Staffler are currently or were in the past employed by AFFiRiS AG.

Atbin Djamshidian reports receiving honoraria from Abbvie and Biogen.

Wassilios Meissner reports fees for editorial activities with Springer Nature and Elsevier, consultancy fees from Lundbeck and Biohaven, and teaching honoraria from UCB.

Olivier Rascol has acted as a scientific advisor for drug companies developing antiparkinsonian medications (AbbVie, Adamas, Acorda, Addex, Aguettant, Alkahest, AlzProtect, Apopharma, Astrazeneca, Bial, Biogen, Britannia, Buckwang, Cerevel, Clevexel, Irlab, Eli-Lilly, Lundbeck, Neuroderm, ONO Pharma, Orion Pharma, Osmotica, Oxford Biomedica, Pfizer, Prexton Therapeutics, Sanofi, Servier, Sunovion, Théranexus, Takeda, Teva, UCB, Watermark Research, XenoPort, XO, Zambon) and has received unrestricted scientific grants from academic non-profit entities (Agence Nationale de la Recherche (ANR), CHU de Toulouse, France-Parkinson, INSERM-DHOS Recherche Clinique Translationnelle, MJ Fox Foundation, Programme Hospitalier de Recherche Clinique du Ministère de la Santé, European Commission (FP7, H2020).

Figures

Fig. 1
Fig. 1
PD03A phase 1 study scheme.
Fig. 2
Fig. 2
Patient disposition.
Fig. 3
Fig. 3
Geometric mean antibody titers over time for (A) PD03A peptide and (B) native target sequence on α-synuclein.
See this image and copyright information in PMC

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