Status:
Completed
Clinicaltrials.gov identifier:
Sponsor:
Affiris
Enrollment:
32
Study Design:
The Phase 1 AFF008 series comprised 4 consecutive studies - AFF008, AFF008E, AFF008A and AFF008AA. In total, 32 patients were enrolled, 24 of them receiving active treatment and 8 PD patients only on standard of care medication, who served as an observational comparison group.
The active group were randomized to receive four immunizations with either low dose (15μg) or high dose (75μg) AFFITOPE® PD01A in intervals of four weeks on an outpatient basis (study AFF008). Eight patients were in an untreated, observational control group.
Twenty-one patients in the PD01A treatment groups and five in the observational group completed the entire series of studies. At screening, the average time of PD after the first diagnosis was 2.6 years. Patients were allowed to continue their standard of care PD medication.
An additional observational follow-up period of twelve months was added (study AFF008E). Part three of the study series (AFF008A) administered a booster immunization after rerandomizing patients from study AFF008E into two different doses of boost (15μg or 75μg AFFITOPE® PD01A). The reboost study (AFF008AA) gave a second booster with a fixed dose of 75μg AFFITOPE® PD01A to patients previously immunized five times. Key objectives were to show safety and tolerability as well as immunogenicity of AFFITOPE® PD01A in a long-term treatment setting.
Results:
Both doses of AFFITOPE® PD01A were locally and systemically well tolerated1. No study drug-related serious adverse events (SAE) or suspected unexpected serious adverse reactions (SUSAR) occurred. Systemic adverse events were very similar to those in patients on standard of care treatment. The majority of adverse events, approximately 55%, were local reactions (LRs), the great majority of LRs being only mild and without dose dependency.
AFFITOPE® PD01A showed a clear immune response against the peptide itself and cross-reactivity against α-synuclein targeted epitope over time. The first boost immunization produced a significant effect on all analysed titers, resulting in the maximum titers observed in this series of studies. The second boost immunization further stabilized the produced antibody titers. Thus, a significant increase in titers against PD01A was seen over time, which translated into a humoral immune response against α-synuclein, being approximately one order of magnitude lower. In addition, PD01-specific antibodies were detectable in cerebrospinal fluid.
Data from post-hoc analyses indicate that AFFITOPE® PD01-induced antibodies preferentially bind to both oligomeric and fibrillar α-synuclein when compared with monomers and showed that there was a trend in reduction of oligomeric α-synuclein levels in plasma as well as cerebrospinal fluid upon treatment with PD01A at week 26.
Clinical scores for PD were stable during the entire study period, however, the study was not designed and not powered to evaluate clinical efficacy.
The logical next step is a Phase 2 study to further evaluate safety and tolerability and to gain early insight into clinical efficacy.
