A Phase 1 Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study to Evaluate the Safety, Tolerability, and Immunogenicity of UBITh® CGRP Immunotherapy (UB-313) in Healthy Participants
Phase: PHASE1
Conditions: Migraine
Sponsor: Vaxxinity, Inc.

 
 
 
CLINICAL TRIAL PROTOCOL 
 
 
 
 
 
Investigational Product: 
UBITh® CGRP Immunotherapy (UB-313) 
 
A Phase 1 Randomized, Double-Blind, Placebo-Controlled, First-in-Human 
Study to Evaluate the Safety, Tolerability, and Immunogenicity of UBITh® 
CGRP Immunotherapy (UB-313) in Healthy Participants 
 
 
EudraCT: 2022-000798-19 
 
 
 
 
 
 
Protocol Number: 
UB-313-101 
 
Final Version 3.0
Date: 13 APRIL 2023
 
 
 
This document contains confidential information and is the property of Vaxxinity Ltd. (Vaxxinity, further referred 
to as the Sponsor). The receiver(s) of this document understand(s) and agree(s) that this document is not to be 
disclosed to any unauthorized third party without prior written agreement issued by the Sponsor. The need to 
disclose certain information contained in this document for the purpose of obtaining informed consent from 
potential participants or their legally acceptable representative(s) will be considered as exceptions. 
 

 
Clinical Trial Protocol  
      UB-313-101 Final Version 3.0, 13 April 2023 
 
 
 
CONFIDENTIAL 
Page 2 of 9 
SYNOPSIS 
Protocol Number 
UB-313-101 
Title of Study 
A Phase 1 Randomized, Double-Blind, Placebo--Controlled, First-in-Human 
Study to Evaluate the Safety, Tolerability, and Immunogenicity of UBITh® 
CGRP Immunotherapy (UB-313) in Healthy Adults 
Study Site 
This study will be conducted at one study center (Center for Clinical 
Pharmacology) in Leuven, Belgium 
Development Phase 
Phase 1, First-in-human 
Study Objectives 
Primary Objectives:  
 
To evaluate the safety and tolerability of UB-313, when administered at 
selected dose regimens given intramuscularly (IM) to healthy adults.  
 
To evaluate the anti-calcitonin gene-related peptide (anti-CGRP) specific 
antibody responses to selected UB-313 dose regimens in healthy adults.   
Secondary Objective: 
 
To evaluate the effects of selected UB-313 dose regimens on capsaicin-
induced dermal blood flow (DBF) as a surrogate marker of target 
engagement. 
Exploratory Objectives: 
 
To evaluate the effects of selected UB-313 dose regimens on CGRP 
concentrations in serum.  
 
To characterize antibodies generated by UB-313. 
 
To examine cytokine release induced by UB-313. 
Endpoints 
Primary Endpoints 
Safety will be assessed by adverse events (AEs), adverse events of special 
interest (AESIs), medically attended adverse events (MAAEs), local (injection 
site) and systemic (generalized) reactions (i.e., reactogenicity), clinical 
laboratory assessments (e.g., chemistry, hematology, urinalysis), vital signs, 
neurological and physical examinations, and electrocardiograms (ECGs) 
through the end of study.  
Immunogenicity will be measured by serum anti-CGRP antibody titers and 
analyzed from baseline to Week 16 and through the end of study (Week 44).  
Secondary Outcome Measure/Endpoints 
Pharmacodynamics (PD) of the immune response will be measured by the 
inhibition of capsaicin-induced increase in DBF and analyzed from baseline to 
Week 16 and either until return to baseline or until Week 44, whichever comes 
first. 
Exploratory Outcome Measures/Endpoints 
Exploratory outcome measures may include but are not limited to the 
following: 
 
CGRP concentrations in serum through the end of study.  
 
Antibody titers against components of UB-313 (i.e., CpG1 and UBITh1) 
through the end of study. 
 
Isotype-specific anti-CGRP antibody titers through the end of study. 
 
Cytokine release from peripheral blood mononuclear cells stimulated with 
a component of UB-313 (T-cell ELISpot) through Week 16. 

 
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Methodology 
This single center, double-blind, placebo-controlled, multidose regimen, first-
in-human (FIH) study of UB-313, an anti-CGRP peptide -based 
immunotherapeutic candidate, is designed to assess the safety, tolerability, and 
immunogenicity of 4 selected UB-313 dose regimens in healthy adults.   
 
Screening Period 
All participants will undergo Laser Speckle Contrast Imaging (LSCI) 
assessments at Screening to ensure a capsaicin response of at least 100% 
increase in DBF. 
 
Following Screening, all eligible participants (approximately 40) will be 
randomized to receive 3 IM injections of UB-313 or placebo in a staggered 
manner by cohort as described below. 
 
Investigational Product Dosage and Schedule:  
Cohort 
Number of 
Participants 
Dose Regimen (0.5mL) 
 
 
Week 1  
  Week 4   
Week 12 
1  
(N=10) 
8  
100 μg   
100 μg  
100 μg  
2 
Placebo 
Placebo  
Placebo 
2 
(N=10) 
8 
300 μg   
100 μg  
100 μg  
2 
Placebo 
Placebo  
Placebo 
3 
(N=10) 
8 
300 μg   
300 μg  
300 μg  
2 
Placebo 
Placebo  
Placebo 
4 
(N=10) 
8 
  600 μg 
100 μg  
100 μg  
2 
Placebo 
Placebo  
Placebo 
 
 
Double-Blind Period 
Eligible healthy participants will be enrolled into 1 of the 4 cohorts, as 
previously described. For safety purposes, dosing of all cohorts will be 
staggered. Sentinel dosing will be performed in Cohorts 1 (first dose of 
100 g), 2 (first dose of 300 g), and 4 (first dose of 600 g). The remaining 
participants in a cohort may be enrolled following a safety review conducted at 
least 24-hours after sentinel dosing; however, no more than 4 participants will 
be dosed within a 24-hour period. 
 
Once all escalation safety evaluable participants within each of the dose levels 
(100 μg for Cohort 1, and 300 μg in Cohorts 2 and 3) have been observed for 
1 week following their first dose of study Investigational Medicinal Product 
(IMP), all available safety data will be reviewed by the Safety Review 
Committee (SRC) before progressing to the next higher dose cohort (100 μg to 
300 μg to 600 μg).  

 
Clinical Trial Protocol  
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Cohort 3 may begin dosing at least 24 hours after all participants in Cohort 2 
have received their first dose, and available (blinded) safety and tolerability 
data have been reviewed by the SRC. Based on the available data, a decision 
will be made to begin dosing of Cohort 3. 
 
Participants will be provided with a diary. Starting the day of IMP 
administration, they will fill in the diary daily for 7 days, recording their 
temperature, and any solicited local and systemic symptoms of reactogenicity.  
 
Capsaicin Challenge  
 
A capsaicin-induced increase in DBF model will be used to assess the PDs of 
the UB-313-mediated immune response. Personnel who will perform these 
assessments will not be involved in UB-313 safety and tolerability evaluation 
due to the potential of unblinding. The capsaicin challenge will be conducted at 
Screening, Baseline before the first dose, and every 4 weeks up to Week 20 and 
subsequently every 8 weeks until the end of study at Week 44. After Week 16, 
LSCI assessment may no longer be required once the average capsaicin 
induced DBF increase within that cohort has returned to baseline (i.e., DBF 
response ±2 SD before administration of IMP within a cohort).  
Total Expected Number 
of Participants 
Approximately 40 eligible healthy male and female participants (10 per cohort) 
will be enrolled to receive UB-313 or placebo.  
Main Inclusion Criteria 
Full details of inclusion criteria are listed in the protocol.  The main inclusion 
criteria include:  
 
 
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.  
Main Exclusion Criteria 
Full details of exclusion criteria are listed in the protocol.  The main exclusion 
criteria include:  
 
 
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. 

 
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 
Has not demonstrated at least a 100% increase in DBF following capsaicin 
challenge as part of Screening procedures and measured through LSCI. 
Investigational Medicinal 
Product 
UB-313 drug product is a synthetic CGRP peptide-based immunotherapy 
formulated in CpG1 and Adju-Phos®. It is provided in single dose vial (peptide: 
100 μg, 300 μg, or 600 μg; dosage volume: 0.5 mL).  
 
Placebo is 0.9% sodium chloride (normal saline), preservative free for 
injection. 
 
IMP will be either UB-313 or placebo and can also be referred to as study drug. 
Participation Duration 
The total study participation will last up to 48 weeks, including: 
Screening period: up to 4 weeks 
Double-blind period: 44 weeks  
Statistical Considerations  As this is an FIH study, the sample size is based on the exploratory nature of 
the design. No statistical power to be considered to determine the sample size.   
 
Primary time-points for immunogenicity and PD are two-fold: 
a) First phase at the end of Week 16 for evaluating maximal 
immuno-responses elicited by the 4 dosage regimens (i.e., cohorts) of UB-
313  
b) Second phase of response maintenance period after Week 16 until the end 
of study (Week 44), in which effects of the 4 dosage regimens of UB-313 
on the duration of responses will be evaluated.  
 
When any cohort completes Week 16, first phase analyses can be conducted 
based on cleaned cohort data up to Week 16. To maintain blinding for the 
remainder of the study, the first phase analyses will be conducted and reviewed 
only by a designated and independent team before the end of study final 
database lock. The purpose of the early analyses of first phase data prior to the 
completion of the study is to have an early read out of the first part of the 
primary immunogenicity and PD results to refine the development plan. Design 
of the second phase of the study will not be changed based on results from the 
first phase data.  
 
 

 
Clinical Trial Protocol  
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Table 1: 
Study Schedule of Assessments  
The Investigator may perform visits outside of the scheduled study visits (unscheduled visits) listed in the Schedule of Assessments table to conduct 
evaluations or assessments required to protect the well-being of the participant. 
Visit Number1 
Screen2 
V12,5 
V1a5 
V1b5 
V2 
V35 
V3a5 
V3b5 
V4 
V5 
V65 
V6a5 
V6b5 
V7 
V8 
V9,  
V10, 
V11 
V12/ET 
Week 
Up to 4 
wks 
W0 
W1 
W4 
W5 
W8 
W12 
W13 
W16 
W20,  
W28, 
W36 
W44 
Day (Visit 
Window) 
-28 to -
1 
D1  
(-3D) 
D1 
-- 
D2 
 
D3 
 
D8  
(±3D) 
D29 
(-3D) 
D29  
(±3D) 
D30 
 
D31 
 
D36  
(±3D) 
D57 
(±5D) 
D85  
(-3D) 
D85  
(±3D) 
D86 
D87 
 
D92  
(±3D) 
D113  
(±7D) 
D141,  
D197, 
D253 
(±14D) 
D309  
(±14D) 
Visit Type 
SRN 
Pre 
IMP 
IMP 
CRU 
TC 
CRU 
Pre 
IMP 
IMP 
CRU 
TC 
CRU 
CRU 
Pre 
IMP 
IMP 
CRU 
TC 
CRU 
EoT 
CRU 
CRU 
 
EoS/ET 
CRU 
General Assessments and Procedures 
Informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
assessment 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication 
review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE/SAE 
review3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Investigational Medicinal Product Administration and Assessments 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IMP Injection18 
 
 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Solicited local 
and systemic 
reactions 
assessment  
 
 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Extended unit 
stay5 
 
 
X5 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Diary review10 
 
 
X 
X 
 
X 
 
X 
X 
 
X 
 
 
X 
X 
 
X 
 
 
 
General Safety Assessments 
Vital signs (pre- 
and post-IMP)6,7 
X 
 
X 
X 
 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Visit Number1 
Screen2 
V12,5 
V1a5 
V1b5 
V2 
V35 
V3a5 
V3b5 
V4 
V5 
V65 
V6a5 
V6b5 
V7 
V8 
V9,  
V10, 
V11 
V12/ET 
Week 
Up to 4 
wks 
W0 
W1 
W4 
W5 
W8 
W12 
W13 
W16 
W20,  
W28, 
W36 
W44 
Day (Visit 
Window) 
-28 to -
1 
D1  
(-3D) 
D1 
-- 
D2 
 
D3 
 
D8  
(±3D) 
D29 
(-3D) 
D29  
(±3D) 
D30 
 
D31 
 
D36  
(±3D) 
D57 
(±5D) 
D85  
(-3D) 
D85  
(±3D) 
D86 
D87 
 
D92  
(±3D) 
D113  
(±7D) 
D141,  
D197, 
D253 
(±14D) 
D309  
(±14D) 
Visit Type 
SRN 
Pre 
IMP 
IMP 
CRU 
TC 
CRU 
Pre 
IMP 
IMP 
CRU 
TC 
CRU 
CRU 
Pre 
IMP 
IMP 
CRU 
TC 
CRU 
EoT 
CRU 
CRU 
 
EoS/ET 
CRU 
Weight 
X 
 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
X 
X 
X 
Physical exam4,8 
X 
 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
X 
Neurological 
exam4,8 
X 
 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
X 
Triplicate 
ECGs4 
X 
 
X 
 
 
X 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
X 
X 
MRI17   
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Laboratory Assessments4,9 
HIV, HCV, 
HBV 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical 
chemistry4 
X 
X 
 
 
 
X 
X 
 
 
 
X 
X 
X 
 
 
 
X 
X 
 
X 
Hematology4  
X 
X 
 
 
 
X 
X 
 
 
 
X 
X 
X 
 
 
 
X 
X 
 
X 
Urinalysis4 
X 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
Urine drug 
screen4 
X 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Pre-IMP 
alcohol breath 
test4  
X 
 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Pre-IMP 
pregnancy 
test4,11  
X 
 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
FSH11  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inflammatory 
markers4,12 
X 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
Cytokine panel 
(pre- and post-
IMP)13 
 
X 
X 
 
 
 
X 
X 
 
 
 
 
X 
X 
 
 
 
 
 
 
Pharmacodynamic Assessments4 
Serum 
antibodies4,14 
 
X 
 
 
 
X 
X 
 
 
 
X 
X 
X 
 
 
 
X 
X 
X 
X 
Serum CGRP4 
 
X 
 
 
 
X 
X 
 
 
 
X 
X 
X 
 
 
 
X 
X 
X 
X 

 
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Visit Number1 
Screen2 
V12,5 
V1a5 
V1b5 
V2 
V35 
V3a5 
V3b5 
V4 
V5 
V65 
V6a5 
V6b5 
V7 
V8 
V9,  
V10, 
V11 
V12/ET 
Week 
Up to 4 
wks 
W0 
W1 
W4 
W5 
W8 
W12 
W13 
W16 
W20,  
W28, 
W36 
W44 
Day (Visit 
Window) 
-28 to -
1 
D1  
(-3D) 
D1 
-- 
D2 
 
D3 
 
D8  
(±3D) 
D29 
(-3D) 
D29  
(±3D) 
D30 
 
D31 
 
D36  
(±3D) 
D57 
(±5D) 
D85  
(-3D) 
D85  
(±3D) 
D86 
D87 
 
D92  
(±3D) 
D113  
(±7D) 
D141,  
D197, 
D253 
(±14D) 
D309  
(±14D) 
Visit Type 
SRN 
Pre 
IMP 
IMP 
CRU 
TC 
CRU 
Pre 
IMP 
IMP 
CRU 
TC 
CRU 
CRU 
Pre 
IMP 
IMP 
CRU 
TC 
CRU 
EoT 
CRU 
CRU 
 
EoS/ET 
CRU 
PBMC for 
ELISpot4   
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Blood 
collection for 
research 
sample4,15 
 
X 
 
 
 
X 
X 
 
 
 
X 
X 
X 
 
 
 
X 
X 
X 
X 
HLA typing 
(optional) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X19 
X19 
Laser imaging 
and capsaicin 
challenge4 
X 
X 
 
 
 
 
X 
 
 
 
 
X 
X 
 
 
 
 
X 
X16 
X16 
Abbreviations: AE = adverse event; CRU = Clinical Research Unit; D = day; DBF = dermal blood flow; ECG = electrocardiogram; EoS = End of Study; EoT = End of Treatment; ET = Early 
Termination; FSH = follicle-stimulating hormone; H = hour; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; IM = intramuscular; IMP = 
investigational medicinal product; LSCI = Laser Speckle Contrast Imaging; MRI = magnetic resonance imaging; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; SAE = 
serious adverse event; SD = standard deviation; SRN = Screening; TC = telephone call, V = visit  
 
1. 
The Investigator may perform visits outside of the scheduled study visits (unscheduled visits) listed in the table to conduct evaluations or assessments required to protect the well-being 
of the participant.  
2. 
Screening and V1 visits can be rescheduled, and Screening window may be extended.  
3. 
AEs/SAEs recording from time of informed consent up to and including Follow-up or ET.  
4. 
On IMP administration days, all laboratory, PD, and capsaicin assessments are to be performed prior to IMP administration.   
5. 
After each IMP administration, (a) participants will stay for 6 hours (±2 hours) after injection for safety observation (except for sentinel participants who will stay for 24 hours after the 
first dose), (b) participants (except the sentinels’ first dose) will have an approximately 24-hour onsite safety review including review of vital signs, temperature, diary, AEs, and 
medications, (c) all participants will have a telephone call approximately 48-hours post IMP injection for safety check including AE and medication review, and (d) all participants will 
complete a diary daily for 7 days, starting from the day of IMP administration. 
6. 
On IMP administration days, vital signs (including temperature) will be measured before and after IMP administration. 
7. 
Participants should be resting in a semi-recumbent position for at least 10 minutes before vital signs measurements. Semi-recumbent vital signs will include heart rate, systolic and 
diastolic blood pressure, respiratory rate, and body temperature. 
8. 
Full neurological and physical examinations are to be performed during Screening, at Week 16 (EoT), Week 44 (EoS), and ET; brief (targeted) examinations may be performed at all 
other visits.  
9. 
Laboratory assessments are detailed in Section 7.7 and Appendix 1. 

 
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10. 
A diary will be dispensed on Day 1. Participants will complete it for 7 days daily, starting on the day of each administration of IMP. 
11. 
For females of childbearing potential only, blood pregnancy test at Screening and urine test at other visits. For females of nonchildbearing potential in post-menopausal state, FSH at 
screening.   
12. 
Inflammatory measures in blood will include but are not limited to C-reactive protein and erythrocyte sedimentation rate. At Screening only, antinuclear antibody, IgM rheumatoid 
factor, and anti-cyclic citrullinated peptide. 
13. 
Cytokine blood samples will be collected pre-dose and approximately 6 hours (±2 hours) post-dose, and only analyzed at the Investigator’s discretion if clinically indicated; otherwise, 
they will be analyzed at the EoT visit. The cytokine panel will include but is not limited to IFN-γ, IL-2, IL-4, IL-6, IL-8, and TNF-α. 
14. 
Antibody measures in blood, including but not limited to anti-CGRP target epitope, anti-UBITh, anti-CpG1, and isotyping of anti-CGRP antibodies.  
15. 
A sample to be obtained as allowed by local regulations and participant consent. 
16. 
After Week 16, LSCI assessment may no longer be required once the average capsaicin-induced DBF increase within that cohort has returned to baseline (i.e., DBF response ±2 SD 
before administration of IMP within a cohort).   
17. 
Historic MRI within 90 days of Screening may be accepted. 
18. 
IMP should be administered to the opposite arm that was used to take blood. Alternate arms should be used for injection visits and the arm used for IMP administration should be 
recorded. 
19. 
A blood sample to be obtained for HLA typing at any post-Week 16 visit as allowed by participant consent. Blood sample is only to be collected at one visit.