1st patient dosed in Phase 2 trial testing vaccine for Parkinson’s
Vaccine targets toxic alpha-synuclein, aims to prevent nerve cell degeneration
The first patient has been dosed in a Phase 2 clinical trial testing AC Immune’s ACI-7104.056, an investigational vaccine targeting toxic alpha-synuclein forms to prevent nerve cell degeneration in Parkinson’s disease.
AC Immune expects to complete the enrollment of the first group of patients in the VacSYn Phase 2 clinical trial (NCT06015841) and deliver initial safety findings by the year’s end.
The study is now underway at several sites in Germany and Spain, and recruitment is ongoing at certain Spanish sites.
“We continue to progress our pipeline … [with] our [alpha-synuclein] active immunotherapy, ACI-7104.056,” Andrea Pfeifer, AC Immune’s CEO, said in a company press release, noting that three of its treatments will be “in mid- to late-stage clinical testing for neurodegeneration” by the end of this year.
“With further clinical readouts from our precision medicine pipeline ahead, we continue to work diligently towards earlier diagnosis and treatment to prevent progression of neurodegenerative diseases,” Pfeifer added.
ACI-7104.056 developed based on earlier Parkinson’s vaccine
Parkinson’s disease is caused by the progressive dysfunction and death of dopaminergic neurons — nerve cells that are responsible for producing dopamine, a brain chemical neurons use to communicate with each other.
A hallmark of Parkinson’s is the formation of toxic protein clumps, or aggregates, inside neurons, mainly composed of the alpha-synuclein protein. These protein clumps are thought to contribute to neuronal dysfunction and death, and as such, therapeutic strategies to reduce alpha-synuclein are expected to alter the disease’s course.
ACI-7104.056 is an optimized vaccine formulation designed to induce alpha-synuclein-specific antibodies that recognize the toxic protein clumps.
The advancement of ACI-7104.056 into a Phase 2 study was based on Phase 1 data from a predecessor experimental vaccine — dubbed Affitope PD01A and developed by Affiris — tested in people with early Parkinson’s disease. In July 2021, AC Immune acquired Affiris’ anti-alpha-synuclein programs.
The Phase 1 AFF008 clinical trial (NCT01568099) demonstrated that Affitope PD01A was safe and well tolerated in patients receiving the vaccine injections once monthly for one year, in addition to standard treatment.
In the follow-up Phase 1 AFF008A trial (NCT 02216188), patients were randomly assigned to receive a single injection of the vaccine to boost their immune reaction. After one year, they received a second so-called boost in the Phase 1 AFF008AA study (NCT02618941). A total of 21 treated and five control patients completed the entire study series.
Affitope PD01A was found to induce an antibody immune response against alpha-synuclein. The first boost injection induced a significant increase in the production of specific antibodies, while the second further stabilized those levels.
Trial testing safety, efficacy, and tolerability of vaccine
The VacSYn Phase 2 trial will assess ACI-7104.056’s safety, tolerability, efficacy, and pharmacological properties in as many as 150 patients with early-stage Parkinson’s. In the first part of the study, researchers will analyze biomarker data to define the dosing regimen and monitor disease-specific biomarkers.
Subsequently, a second part will aim to obtain clinical proof-of-concept data and monitor disease progression, as well as measuring digital, imaging, and fluid biomarkers.
The trial’s primary goals include the assessment of the frequency and intensity of adverse events, and whether or not they are related to the treatment. Other main goals are the number of participants with abnormal magnetic resonance imaging (MRI) data or with clinically significant changes in physical and neurological examinations.
The blood levels of specific alpha-synuclein antibodies generated by the vaccine also will be measured.
The trial also will evaluate the levels of alpha-synuclein antibodies in other fluids, particularly the cerebrospinal fluid or CSF, the liquid that surrounds the brain and spinal cord). It also will assess levels of dopamine transporter proteins — which are responsible for reabsorbing dopamine back into neurons, and whose levels are reduced in Parkinson’s — in specific brain regions.
Further, changes in motor and nonmotor function will be assessed using the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale, known as MDS-UPDRS.
AC Immune also is developing a positron emission tomography (PET) tracer, called ACI-12589, which can detect deposits of disease-causing alpha-synuclein in the brain. A recently published study included the first-in-human data evaluating ACI-12589 as a diagnostic tool in people with Parkinson’s and other alpha-synuclein-related diseases.