Migraine
Conditions
Brief summary
This first in-human (FIH) study of UB-313, an anti-calcitonin gene-related peptide based immunotherapeutic candidate, is designed to assess the safety, tolerability, and immunogenicity of 4 selected UB-313 dose regimens in healthy adults.
Detailed description
This is a single-site, randomized, double-blind, placebo-controlled, multidose regimen, FIH study of UB-313, an anti-CGRP peptide-based immunotherapy candidate. The double-blind period will include dose escalation and cohort staggering for up to 4 planned dose levels of UB-313 or placebo in 4 cohorts of healthy participants. All eligible participants will be enrolled in the study for up to 44 weeks, consisting of IM injections of UB-313 or placebo at Week 0 (Baseline, Day 1), Week 4, and Week 12. The End of Treatment (EoT) is defined as Week 16, followed by a follow-up period up to Week 44.
Interventions
BIOLOGICALUB-313
A synthetic peptide-based immunotherapy
BIOLOGICALPlacebo
Normal saline
Sponsors
Vaxxinity, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Is a male or female aged 18 to 55 years old, inclusive, at time of informed consent. * Has a body mass index between 18 and 30 kg/m2, inclusive at Screening, and with a minimum weight of 50 kg. * Male participants and their partners of childbearing potential must commit to the use of highly effective contraceptives for the study duration and for at least 12 weeks after the last dose. Men must refrain from donating sperm during this same period. * Female participants must be of nonchildbearing potential, or, for women of childbearing potential, must be willing to practice highly effective contraception throughout the duration of the study and for at least 24 weeks following the last dose. * Other inclusion criteria apply
Exclusion criteria
* Has a history of clinically significant medical or psychiatric conditions, which in the opinion of the Investigator may compromise the participant's safety or the scientific value of the study, posing an unacceptable risk to the participant or interfere with the participant's ability to comply with study procedures or abide by study restrictions. * Presents any concern by the Investigator regarding safe participation in the study or for any other reason (including contraindication to MRI) that the Investigator considers the participant inappropriate for participation in the study. * Has a recent history (within the past year of Screening) of migraine headache. * Has unsuitable skin characteristics for the dermal capsaicin challenge as determined by the Investigator. * Has not demonstrated at least a 100% increase in dermal blood flow following capsaicin challenge as part of Screening procedures and measured through laser speckle contrast imaging. * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events | 44 weeks | The number and percentage of participants with TEAEs were tabulated. |
| Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, 28, 36 and 44; Week 0, Week 16 and Week 44 are reported | Immunogenicity measured by blood anti-CGRP antibody titers, reported as Optical Density (OD) of 1:25 dilution. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Weeks 0, 4, 8, 12, 16, 20 | Number of Participants with inhibition of capsaicin-induced increase in dermal blood flow |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| UB-313 Cohort 1 UB-313 100mcg administered by intramuscular (IM) injection at Week 0, Week 4 and Week 12
UB-313: A synthetic peptide-based immunotherapy | 8 |
| UB-313 Cohort 2 UB-313 300mcg administered by IM injection at Week 0 and 100mcg at Week 4 and Week 12
UB-313: A synthetic peptide-based immunotherapy | 8 |
| UB-313 Cohort 3 UB-313 300mcg administered by IM injection at Week 0, Week 4 and Week 12
UB-313: A synthetic peptide-based immunotherapy | 8 |
| UB-313 Cohort 4 UB-313 600mcg administered by IM injection at Week 0 and 100mcg at Week 4 and Week 12
UB-313: A synthetic peptide-based immunotherapy | 8 |
| Placebo Comparator Placebo (normal saline), administered by IM injection at Week 0, Week 4 and Week 12
Placebo: Normal saline | 8 |
| Total | 40 |
Baseline characteristics
| Characteristic | UB-313 Cohort 1 | Total | Placebo Comparator | UB-313 Cohort 4 | UB-313 Cohort 3 | UB-313 Cohort 2 |
|---|---|---|---|---|---|---|
| Age, Continuous | 35.1 years STANDARD_DEVIATION 13.66 | 31.1 years STANDARD_DEVIATION 10.32 | 26.0 years STANDARD_DEVIATION 8.88 | 30.4 years STANDARD_DEVIATION 7.87 | 31.6 years STANDARD_DEVIATION 11.92 | 32.5 years STANDARD_DEVIATION 8.52 |
| BMI | 25.39 kg/m2 STANDARD_DEVIATION 3.388 | 23.76 kg/m2 STANDARD_DEVIATION 2.931 | 23.68 kg/m2 STANDARD_DEVIATION 2.6 | 21.88 kg/m2 STANDARD_DEVIATION 2.384 | 24.29 kg/m2 STANDARD_DEVIATION 3.624 | 23.58 kg/m2 STANDARD_DEVIATION 1.834 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 40 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Female | 3 Participants | 21 Participants | 4 Participants | 5 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 19 Participants | 4 Participants | 3 Participants | 2 Participants | 5 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 7 / 8 | 8 / 8 | 6 / 8 | 8 / 8 | 7 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Immunogenicity Measured by Serum Anti-CGRP Antibodies.
Immunogenicity measured by blood anti-CGRP antibody titers, reported as Optical Density (OD) of 1:25 dilution.
Time frame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, 28, 36 and 44; Week 0, Week 16 and Week 44 are reported
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UB-313 Cohort 1 | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 0 (Baseline) | 0.5161 Optical Density (OD) | Standard Deviation 0.1697 |
| UB-313 Cohort 1 | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 44 (EoS) | 1.4449 Optical Density (OD) | Standard Deviation 0.8055 |
| UB-313 Cohort 1 | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 16 (EoT) | 2.7271 Optical Density (OD) | Standard Deviation 1.2042 |
| UB-313 Cohort 2 | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 16 (EoT) | 2.1900 Optical Density (OD) | Standard Deviation 1.0378 |
| UB-313 Cohort 2 | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 0 (Baseline) | 0.4720 Optical Density (OD) | Standard Deviation 0.1688 |
| UB-313 Cohort 2 | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 44 (EoS) | 1.2225 Optical Density (OD) | Standard Deviation 0.576 |
| UB-313 Cohort 3 | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 16 (EoT) | 3.2903 Optical Density (OD) | Standard Deviation 0.7628 |
| UB-313 Cohort 3 | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 0 (Baseline) | 0.6024 Optical Density (OD) | Standard Deviation 0.2292 |
| UB-313 Cohort 3 | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 44 (EoS) | 1.7653 Optical Density (OD) | Standard Deviation 0.9176 |
| UB-313 Cohort 4 | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 0 (Baseline) | 0.5495 Optical Density (OD) | Standard Deviation 0.0994 |
| UB-313 Cohort 4 | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 44 (EoS) | 1.5401 Optical Density (OD) | Standard Deviation 0.7779 |
| UB-313 Cohort 4 | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 16 (EoT) | 3.0731 Optical Density (OD) | Standard Deviation 0.9075 |
| Placebo Comparator | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 16 (EoT) | 0.4776 Optical Density (OD) | Standard Deviation 0.0861 |
| Placebo Comparator | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 0 (Baseline) | 0.4900 Optical Density (OD) | Standard Deviation 0.0862 |
| Placebo Comparator | Immunogenicity Measured by Serum Anti-CGRP Antibodies. | Week 44 (EoS) | 0.5614 Optical Density (OD) | Standard Deviation 0.1321 |
Primary
Number of Participants With Treatment-Emergent Adverse Events
The number and percentage of participants with TEAEs were tabulated.
Time frame: 44 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| UB-313 Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events | 7 Participants |
| UB-313 Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events | 8 Participants |
| UB-313 Cohort 3 | Number of Participants With Treatment-Emergent Adverse Events | 6 Participants |
| UB-313 Cohort 4 | Number of Participants With Treatment-Emergent Adverse Events | 8 Participants |
| Placebo Comparator | Number of Participants With Treatment-Emergent Adverse Events | 7 Participants |
Secondary
Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow
Number of Participants with inhibition of capsaicin-induced increase in dermal blood flow
Time frame: Weeks 0, 4, 8, 12, 16, 20
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UB-313 Cohort 1 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Baseline | 0 Participants |
| UB-313 Cohort 1 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 4 | 1 Participants |
| UB-313 Cohort 1 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 8 | 0 Participants |
| UB-313 Cohort 1 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 12 | 0 Participants |
| UB-313 Cohort 1 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 16 | 0 Participants |
| UB-313 Cohort 1 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 20 | 0 Participants |
| UB-313 Cohort 2 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 16 | 0 Participants |
| UB-313 Cohort 2 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 20 | 0 Participants |
| UB-313 Cohort 2 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Baseline | 1 Participants |
| UB-313 Cohort 2 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 8 | 0 Participants |
| UB-313 Cohort 2 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 12 | 0 Participants |
| UB-313 Cohort 2 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 4 | 0 Participants |
| UB-313 Cohort 3 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 12 | 0 Participants |
| UB-313 Cohort 3 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 16 | 0 Participants |
| UB-313 Cohort 3 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Baseline | 0 Participants |
| UB-313 Cohort 3 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 8 | 0 Participants |
| UB-313 Cohort 3 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 4 | 0 Participants |
| UB-313 Cohort 3 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 20 | 0 Participants |
| UB-313 Cohort 4 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 12 | 0 Participants |
| UB-313 Cohort 4 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 4 | 0 Participants |
| UB-313 Cohort 4 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 8 | 0 Participants |
| UB-313 Cohort 4 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 20 | 0 Participants |
| UB-313 Cohort 4 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 16 | 0 Participants |
| UB-313 Cohort 4 | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Baseline | 0 Participants |
| Placebo Comparator | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 16 | 1 Participants |
| Placebo Comparator | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 8 | 0 Participants |
| Placebo Comparator | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 4 | 0 Participants |
| Placebo Comparator | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 20 | 0 Participants |
| Placebo Comparator | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Week 12 | 1 Participants |
| Placebo Comparator | Pharmacodynamics of the Immune Response Measured by Capsaicin-induced Increase in Dermal Blood Flow | Baseline | 0 Participants |