Parkinsonism, Parkinson's Disease
Conditions
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.
Interventions
BIOLOGICALPlacebo
Matching placebo
BIOLOGICALUB-312
A synthetic peptide-based vaccine
Sponsors
Centre for Human Drug Research, Netherlands
Worldwide Clinical Trials
Vaxxinity, Inc.
United Neuroscience Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse Events | 44 weeks | Number of AEs will be assessed |
| Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood | 44 weeks | Number of Participants with Anti-aSyn Antibodies in Blood from Weeks 1 through 45. |
| Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF | 44 weeks | Number of Participants with Anti-aSyn Antibodies in CSF from Weeks 1 through 45. |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A: UB-312 40 mcg UB-312 40 mcg by intramuscular injection at Weeks 1, 5 and 13
UB-312: A synthetic peptide-based vaccine | 6 |
| Part A: UB-312 100 mcg UB-312 100 mcg by intramuscular injection at Weeks 1, 5 and 13
UB-312: A synthetic peptide-based vaccine | 6 |
| Part A: UB-312 40/300 mcg UB-312 40 mcg at Week 1 and 300 mcg at Weeks 5 and 13 by intramuscular injection
UB-312: A synthetic peptide-based vaccine | 6 |
| Part A: UB-312 300 mcg UB-312 300 mcg by intramuscular injection at Weeks 1, 5 and 13
UB-312: A synthetic peptide-based vaccine | 6 |
| Part A: UB-312 40/1000 mcg UB-312 40 mcg at Week 1 and 1000 mcg at Weeks 5 and 13 by intramuscular injection
UB-312: A synthetic peptide-based vaccine | 6 |
| Part A: UB-312 1000 mcg UB-312 1000 mcg by intramuscular injection at Weeks 1, 5 and 13
UB-312: A synthetic peptide-based vaccine | 6 |
| Part A: UB-312 2000 mcg UB-312 2000 mcg by intramuscular injection at Weeks 1, 5 and 13
UB-312: A synthetic peptide-based vaccine | 6 |
| Part A: Placebo Placebo by intramuscular injection at Weeks 1, 5 and 13
Placebo: Matching placebo | 8 |
| Part B: UB-312 300/100 mcg UB-312 300 mcg at Week 1 and 100 mcg at Weeks 5 and 13 by intramuscular injection
UB-312: A synthetic peptide-based vaccine | 7 |
| Part B: UB-312 300 mcg UB-312 300 mcg at Weeks 1, 5 and 13 by intramuscular injection
UB-312: A synthetic peptide-based vaccine | 7 |
| Part B: Placebo Placebo by intramuscular injection at Weeks 1, 5 and 13
Placebo: Matching placebo | 6 |
| Total | 70 |
Baseline characteristics
| Characteristic | Part A: UB-312 40 mcg | Total | Part B: Placebo | Part B: UB-312 300 mcg | Part B: UB-312 300/100 mcg | Part A: Placebo | Part A: UB-312 2000 mcg | Part A: UB-312 1000 mcg | Part A: UB-312 40/1000 mcg | Part A: UB-312 300 mcg | Part A: UB-312 40/300 mcg | Part A: UB-312 100 mcg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 72.5 years | 66.1 years | 61.0 years | 63.4 years | 67.4 years | 64.6 years | 72.0 years | 68.3 years | 65.0 years | 60.0 years | 68.5 years | 65.0 years |
| Race (NIH/OMB) Other American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Other Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Other Black or African American | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Other More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Other Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Other Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Other White | 6 Participants | 66 Participants | 6 Participants | 7 Participants | 7 Participants | 7 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 5 Participants |
| Region of Enrollment Netherlands | 6 participants | 70 participants | 6 participants | 7 participants | 7 participants | 8 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants |
| Sex: Female, Male Female | 2 Participants | 29 Participants | 1 Participants | 2 Participants | 1 Participants | 4 Participants | 4 Participants | 1 Participants | 2 Participants | 4 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 41 Participants | 5 Participants | 5 Participants | 6 Participants | 4 Participants | 2 Participants | 5 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 7 | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 5 / 6 | 6 / 6 | 5 / 6 | 6 / 6 | 6 / 6 | 6 / 6 | 5 / 6 | 8 / 8 | 7 / 7 | 7 / 7 | 5 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 3 / 7 | 0 / 7 | 0 / 6 |
Outcome results
Primary
Frequency of Adverse Events
Number of AEs will be assessed
Time frame: 44 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: UB-312 40 mcg | Frequency of Adverse Events | 22 TEAEs |
| Part A: UB-312 100 mcg | Frequency of Adverse Events | 31 TEAEs |
| Part A: UB-312 40/300 mcg | Frequency of Adverse Events | 25 TEAEs |
| Part A: UB-312 300 mcg | Frequency of Adverse Events | 31 TEAEs |
| Part A: UB-312 40/1000 mcg | Frequency of Adverse Events | 24 TEAEs |
| Part A: UB-312 1000 mcg | Frequency of Adverse Events | 17 TEAEs |
| Part A: UB-312 2000 mcg | Frequency of Adverse Events | 18 TEAEs |
| Part A: Placebo | Frequency of Adverse Events | 25 TEAEs |
| Part B: UB-312 300/100 mcg | Frequency of Adverse Events | 59 TEAEs |
| Part B: UB-312 300 mcg | Frequency of Adverse Events | 42 TEAEs |
| Part B: Placebo | Frequency of Adverse Events | 20 TEAEs |
Primary
Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood
Number of Participants with Anti-aSyn Antibodies in Blood from Weeks 1 through 45.
Time frame: 44 weeks
Population: Per protocol population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: UB-312 40 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood | 5 Participants |
| Part A: UB-312 100 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood | 5 Participants |
| Part A: UB-312 40/300 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood | 5 Participants |
| Part A: UB-312 300 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood | 6 Participants |
| Part A: UB-312 40/1000 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood | 0 Participants |
| Part A: UB-312 1000 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood | 0 Participants |
| Part A: UB-312 2000 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood | 0 Participants |
| Part A: Placebo | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood | 0 Participants |
| Part B: UB-312 300/100 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood | 5 Participants |
| Part B: UB-312 300 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood | 7 Participants |
| Part B: Placebo | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in Blood | 0 Participants |
Primary
Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF
Number of Participants with Anti-aSyn Antibodies in CSF from Weeks 1 through 45.
Time frame: 44 weeks
Population: per protocol population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: UB-312 40 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF | 1 Participants |
| Part A: UB-312 100 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF | 4 Participants |
| Part A: UB-312 40/300 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF | 3 Participants |
| Part A: UB-312 300 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF | 6 Participants |
| Part A: UB-312 40/1000 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF | 0 Participants |
| Part A: UB-312 1000 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF | 0 Participants |
| Part A: UB-312 2000 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF | 0 Participants |
| Part A: Placebo | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF | 0 Participants |
| Part B: UB-312 300/100 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF | 4 Participants |
| Part B: UB-312 300 mcg | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF | 1 Participants |
| Part B: Placebo | Immunogenicity of UB-312 as Determined by Anti-aSyn Antibodies in CSF | 0 Participants |