Vaccine trial for early Parkinson’s meets primary objectives
UB-312 was well tolerated and able to produce an immune response
UB-312, an experimental vaccine by Vaxxinity, appeared safe and well tolerated and was able to produce an immune response against toxic alpha-synuclein protein aggregates in people with early Parkinson’s disease, according to data from a clinical trial.
According to the company, UB-312 met the primary objectives of the Phase 1 clinical trial (NCT04075318), which consisted of two parts: the first involving healthy adults and the second focusing on individuals with Parkinson’s disease.
The results from both parts of the trial were consistent and deemed promising, indicating a favorable outcome for UB-312. Based on these findings, the company intends to advance to a Phase 2 clinical trial.
“These positive Phase 1 results demonstrate several important features necessary for an immunotherapy against Parkinson’s disease and other synucleinopathies to be successful, and represent a further proof-of-principle for Vaxxinity’s platform in chronic disease,” Mei Mei Hu, CEO of Vaxxinity, said in a company news release. “These results support the further development of UB-312 in a Phase 2 clinical trial. We continue to view UB-312 as a promising candidate for the prevention or disease modification of Parkinson’s disease globally.”
Parkinson’s disease is characterized by the presence of abnormal clumps or tangles of alpha-synuclein protein in the brain. These protein aggregates are believed to play a role in the progression of the disease.
UB-312 stimulates production of antibodies targeting disease-associated alpha-synuclein forms
Vaxxinity’s experimental vaccine, UB-312, incorporates a synthetic fragment of the alpha-synuclein protein and immune-stimulating molecules. The vaccine is specifically designed to stimulate the production of antibodies in the body that target the disease-associated forms of alpha-synuclein. By doing so, UB-312 aims to initiate an immune response that can potentially mitigate the impact of the protein aggregates and stop the development of Parkinson’s disease.
“A vaccine against alpha-synuclein is a revolutionary concept that can be of immense impact in treating neurodegenerative diseases such as Parkinson’s disease and synucleinopathies,” said Geert Jan Groeneveld, MD, PhD, the trial’s principal investigator.
Groeneveld is also chief medical and scientific officer at the Centre for Human Drug Research in Leiden, Netherlands, where the trial took place.
In the initial phase of the placebo-controlled trial, involving 50 healthy volunteers ages 40 to 85, UB-312 demonstrated good tolerability across multiple dosage levels. Most reported side effects were mild, such as headaches and localized reactions at the injection site, which went away on their own.
UB-312 was immunogenic, that is, it produced an immune response against toxic alpha-synuclein protein. Antibodies against abnormal forms of the protein were detected in the blood and cerebrospinal fluid (CSF), the liquid that surrounds the brain and spinal cord. This means the antibodies were able to cross the blood-brain barrier that usually keeps treatments from entering the brain.
Second part of clinical trial
The second part of the trial tested two doses (100 and 300 micrograms) of UB-312 versus a placebo in 20 age-matched people with early Parkinson’s. The trial ran over a 20-week treatment period followed by 24 weeks of observation, during which researchers evaluated the vaccine’s safety, tolerability, and immunogenicity.
Of the 13 participants who completed dosing with UB-312, 12 (92%) developed antibodies against alpha-synuclein that were also detected in the CSF. Two experienced serious side effects, only one of which was deemed possibly related to treatment, and those went away on their own. The safety profile was similar in the UB-312 and placebo groups.
“UB-312 was observed to safely break immune tolerance, inducing antibodies against toxic aggregated forms of alpha-synuclein,” Hu said.
Immune tolerance occurs when the immune system does not mount an immune response against self-antigens, preventing it from attacking normal, healthy cells and tissues.
“Importantly, these antibodies crossed the blood brain barrier, and the data also suggest potential target engagement in the periphery, where pathological [disease-causing] alpha-synuclein is known to be concentrated,” Hu added.
While the trial also included exploratory measures of motor symptoms and cognitive impairment, a common nonmotor symptom of Parkinson’s, it was not designed or powered to detect differences between UB-312 and placebo groups.
The Michael J. Fox Foundation for Parkinson’s Research is now funding a two-year project that Vaxxinity will launch in collaboration with the Mayo Clinic and the University of Texas Houston.
Together, they’ll use a lab technique called protein misfolding cyclic amplification to see how well the antibodies found in the CSF of the trial’s participants can bind to abnormally shaped alpha-synuclein.
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