Study of UB-312 in Healthy Participants and Parkinson's Disease Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease; Parkinsonism
• Intervention / Treatment: Biological: UB-312; Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands
    • Centre for Human Drug Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UB-312 40 mcg; UB-312 40 mcg by intramuscular injection at Weeks 1, 5 and 13	Biological: UB-312; A synthetic peptide-based vaccine
Experimental: UB-312 100 mcg; UB-312 100 mcg by intramuscular injection at Weeks 1, 5 and 13	Biological: UB-312; A synthetic peptide-based vaccine
Experimental: UB-312 40/300 mcg; UB-312 40 mcg at Week 1 and 300 mcg at Weeks 5 and 13 by intramuscular injection	Biological: UB-312; A synthetic peptide-based vaccine
Experimental: UB-312 300 mcg; UB-312 300 mcg by intramuscular injection at Weeks 1, 5 and 13	Biological: UB-312; A synthetic peptide-based vaccine
Experimental: UB-312 40/1000 mcg; UB-312 40 mcg at Week 1 and 1000 mcg at Weeks 5 and 13 by intramuscular injection	Biological: UB-312; A synthetic peptide-based vaccine
Experimental: UB-312 1000 mcg; UB-312 1000 mcg by intramuscular injection at Weeks 1, 5 and 13	Biological: UB-312; A synthetic peptide-based vaccine
Experimental: UB-312 2000 mcg; UB-312 2000 mcg by intramuscular injection at Weeks 1, 5 and 13	Biological: UB-312; A synthetic peptide-based vaccine
Placebo Comparator: Placebo; Placebo by intramuscular injection at Weeks 1, 5 and 13	Biological: Placebo; Matching placebo
Experimental: UB-312 300/100 mcg; UB-312 300 mcg at Week 1 and 100 mcg at Weeks 5 and 13 by intramuscular injection	Biological: UB-312; A synthetic peptide-based vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Adverse Events	Number of AEs will be assessed	44 weeks
Immunogenicity of UB-312 as determined by anti-aSyn antibodies in blood and CSF	Immunogenicity will be measured by change from baseline of blood anti-aSyn antibody titers.	Weeks 1, 2, 5, 6, 9, 13, 14, 17, 21, 29, 37 and 45
Immunogenicity of UB-312 as determined by anti-aSyn antibodies in blood and CSF	Immunogenicity will be measured by change from baseline of CSF anti-aSyn antibody titers	Weeks 1, 21 and 45

Collaborators and Investigators

• Sponsor: United Neuroscience Ltd.
• Collaborators: Worldwide Clinical Trials; Centre for Human Drug Research, Netherlands; Vaxxinity, Inc.
• Investigators: Study Director: Dario Mirski, MD, Vaxxinity, Inc.

Publications and helpful links

General Publications

• Wang CY, Walfield AM. Site-specific peptide vaccines for immunotherapy and immunization against chronic diseases, cancer, infectious diseases, and for veterinary applications. Vaccine. 2005 Mar 18;23(17-18):2049-56. doi: 10.1016/j.vaccine.2005.01.007.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2019
• Primary Completion (Actual): March 1, 2023
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: August 5, 2019
• First Submitted That Met QC Criteria: August 28, 2019
• First Posted (Actual): August 30, 2019

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Parkinsonian Disorders
• Other Study ID Numbers: UB-312-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No