Clinical trial NCT04075318: Study of UB-312 in Healthy Participants and Parkinson's Disease Patients
Official title: A Phase 1 Study to Evaluate the Safety, Tolerability, and Immunogenicity of UBITh® PD Immunotherapeutic Vaccine (UB-312) in Healthy Participants and Participants With Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Parkinsonism
Lead sponsor: United Neuroscience Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Centre for Human Drug Research, Netherlands
name: Worldwide Clinical Trials
name: Vaxxinity, Inc.
First posted: 2019-08-30
Enrollment: 70
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a 44-week, randomized, placebo-controlled, double-blind, single-center, phase 1 clinical trial consisting of a dose-escalation Part A study in healthy participants, followed by a Part B in participants with Parkinson's disease with a selected doses from Part A.

Detailed description: This is a first-in-human Phase 1 study to determine the safety, tolerability, and immunogenicity of UB-312 in healthy participants and in participants with Parkinson's disease (PD). UB-312 is a UBITh®-enhanced synthetic peptide-based vaccine and may provide an active immunotherapy option for treating synucleinopathies including the most prevalent form, PD.

The study consists of two parts. Part A of the study with healthy participants will consist of dose escalation and cohort staggering for up to seven planned dose levels or placebo. Part B of the study will consist of two cohorts of participants with Parkinson's disease (PD). Dosing for Part B will be based on safety, tolerability and immunogenicity from Part A. All eligible participants will be enrolled in a 44-week study consisting of 20 weeks of treatment and 24 weeks of follow-up.

Eligibility criteria: Inclusion Criteria:

* Male or female aged 40 to 85 years old, inclusive at screening
* Expected to be able to undergo all study procedures
* Other inclusion criteria apply

For Part B only:

* A diagnosis of PD, confirmed by a neurologist
* Hoehn \&Yahr Stage ≤ III at Screening
* Stable treatment of permitted antiparkinsonian medications from 30 days prior to first study drug administration or 60 days for MAO-B inhibitors, and expected to remain stable throughout the study

Exclusion Criteria:

* Clinically significant abnormalities, as judged by the investigator
* History of medical, neurological or psychiatric conditions which in the opinion of the investigator may compromise participant's safety or scientific value of the study
* Acute or chronic infection as judged by the investigator, for positive human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV)
* History or evidence of an autoimmune disorder
* History of anergy.
* Participated/participating in any clinical trial with monoclonal antibodies or vaccines directed at aSyn
* Other exclusion criteria apply

For Part B only:

* Other known or suspected cause of Parkinsonism other than idiopathic PD
* History or evidence at Screening of PD-related freezing episodes, falls, or orthostatic hypotension
* Dopamine transporter single-photon emission computerized tomography scan (DaTscan) inconsistent with dopamine transporter deficit.
* Clinically significant neurological disease other than PD

Primary outcomes:
measure: Frequency of Adverse Events
timeFrame: 44 weeks
measure: Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood
timeFrame: 44 weeks
measure: Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF
timeFrame: 44 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research
Study officials:
affiliation: Vaxxinity, Inc.
name: Medical Director, MD
role: STUDY_DIRECTOR
References:
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citation: Wang CY, Finstad CL, Walfield AM, Sia C, Sokoll KK, Chang TY, Fang XD, Hung CH, Hutter-Paier B, Windisch M. Site-specific UBITh amyloid-beta vaccine for immunotherapy of Alzheimer's disease. Vaccine. 2007 Apr 20;25(16):3041-52. doi: 10.1016/j.vaccine.2007.01.031. Epub 2007 Jan 19.
citation: Wang CY, Wang PN, Chiu MJ, Finstad CL, Lin F, Lynn S, Tai YH, De Fang X, Zhao K, Hung CH, Tseng Y, Peng WJ, Wang J, Yu CC, Kuo BS, Frohna PA. UB-311, a novel UBITh(R) amyloid beta peptide vaccine for mild Alzheimer's disease. Alzheimers Dement (N Y). 2017 Apr 14;3(2):262-272. doi: 10.1016/j.trci.2017.03.005. eCollection 2017 Jun.
citation: Eijsvogel P, Misra P, Concha-Marambio L, Boyd JD, Ding S, Fedor L, Hsieh YT, Sun YS, Vroom MM, Farris CM, Ma Y, de Kam ML, Radanovic I, Vissers MFJM, Mirski D, Shareghi G, Shahnawaz M, Singer W, Kremer P, Groeneveld GJ, Yu HJ, Dodart JC. Target engagement and immunogenicity of an active immunotherapeutic targeting pathological alpha-synuclein: a phase 1 placebo-controlled trial. Nat Med. 2024 Sep;30(9):2631-2640. doi: 10.1038/s41591-024-03101-8. Epub 2024 Jun 20.
citation: Yu HJ, Thijssen E, van Brummelen E, van der Plas JL, Radanovic I, Moerland M, Hsieh E, Groeneveld GJ, Dodart JC. A Randomized First-in-Human Study With UB-312, a UBITh(R) alpha-Synuclein Peptide Vaccine. Mov Disord. 2022 Jul;37(7):1416-1424. doi: 10.1002/mds.29016. Epub 2022 Apr 15.