UB-312 Vaccine Well Tolerated by Healthy Adults in Ongoing Trial
UB-312, an experimental vaccine targeting aggregated and toxic forms of alpha-synuclein to treat Parkinson’s disease, was generally well tolerated at multiple doses in a clinical trial in healthy adults.
Study data also suggest that UB-312 prompted an immune response, as designed, against the alpha-synuclein protein.
With two doses now selected for further testing, the Phase 1 trial (NCT04075318) has moved into its second part and is actively recruiting about 20 Parkinson’s patients at its single center in the Netherlands.
Results were in the study, “A Randomized First-in-Human Study With UB-312, a UBITh® α-Synuclein Peptide Vaccine,” published in Movement Disorders.
One of the hallmark molecular features of Parkinson’s is the buildup of abnormal clumps or tangles of alpha-synuclein in the brain. These protein aggregates are thought to drive the disease’s development.
UB-312, by Vaxxinity, is an experimental vaccine that contains a synthetic piece of the alpha-synuclein protein alongside immune-stimulating molecules. It is designed to prompt the body to make antibodies that target disease-associated forms of alpha-synuclein.
In its first part, the Phase 1 clinical trial enrolled 50 healthy adults, ages 40 to 85. All were randomly assigned to placebo injections or those of UB-312 at doses ranging from 40 to 2,000 micrograms, with regular monitoring for almost one year.
The trial’s design had called for each participant to receive three injections on its first, fifth, and 13th week of dosing, followed by monitoring. Those in groups testing doses of 300 micrograms and lower (24 people) finished the trial as planned, except for one participant who was excluded due to initial abnormal laboratory tests.
UB-312 was generally well tolerated at doses up to 300 micrograms given three times, the researchers reported. A total of 96 events were classified as possibly or probably a side effect of the medication; most were headaches and reactions at the vaccination site such as pain or tenderness, which went away on their own in time.
“Local vaccination-site reactions did not increase after subsequent immunizations, and no severe local reactions were observed,” the researchers wrote.
Dosing for groups assigned to UB-312 injections at 1,000 micrograms and above was stopped after the first or second dose. Researchers made this decision after one person twice dosed at 1,000 micrograms developed serious (grade 3) flu-like symptoms, which was deemed an event of interest. Symptoms were managed with over-the-counter pain relievers and resolved in about a day. A participant given the lower, 300 microgram dose had also developed flu-like symptoms that were less severe.
“This type of flu-like reaction is commonly observed with active vaccines containing a potent adjuvant [immune activator]. Similar reactions have been observed for other nonreplicating vaccines, both approved and in clinical development,” the scientists wrote.
They noted that flu-like symptoms usually develop because the immune system is being activated, as intended, by the vaccine.
“Given the self-limiting nature of the flu-like reactions and their resemblance to such events occurring with many other vaccines, we believe the safety and reactogenicity of UB-312 is acceptable and does not preclude further development of doses up to 300 [micrograms],” the researchers added.
Prior to the trial, none of the adults vaccinated with UB-312 had detectable antibodies against alpha-synuclein. However, by trial week nine, all given the experimental vaccine had detectable antibodies against the protein.
Anti-alpha-synuclein antibodies were detectable out to 45 weeks in participants given UB-312 at doses of 100 or 300 micrograms, with the most potent response seen in the six people given three, 300 microgram injections. These six volunteers also had detectable anti-alpha-synuclein antibodies in the fluid that surrounds the brain and spinal cord, called the cerebrospinal fluid or CSF.
“In this first-in-human study, UB-312 was generally safe, well tolerated, and generated robust time- and dose-dependent anti-[alpha-synuclein] antibodies detectable in both serum [blood] and CSF,” the researchers concluded.
“Minimal effects were observed on normal [alpha-synuclein] levels in plasma and CSF,” they added.
Doses of 100 and 300 micrograms were selected to be tested in people with early or mild to moderate Parkinson’s in the ongoing trial’s second portion.
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