Immunogenicity & Safety Study of Adenovirus Type 5 (AD5) Based Oral Norovirus Vaccines

A Phase 1b, Open-label, Boost-optimization Study of an Adenoviral- Vector Based Oral Norovirus Vaccine (VXA-G1.1-NN) Expressing GI.1 VP1 Administered Orally to Healthy Adult Volunteers

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04875676

Acronym

VXA-NVV-105

Enrollment

Registered

2021-05-06

Start date

2021-04-30

Completion date

2022-02-16

Last updated

2024-05-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Norovirus Infections

Brief summary

To evaluate the immunogenicity of VXA-G1.1-NN with repeat-dose administration at Day 1 and varying boost schedules (Week 4, 8 or 12 post initial dose) in healthy adults aged 18-55, inclusive, and to assess the safety and tolerability of VXA- G1.1-NN with repeat-dose administration at varying boost schedules (Week 4, 8 or 12) in healthy adults aged 18-55, inclusive

Interventions

BIOLOGICALVXA-G1.1-NN

Norovirus GI.1 Norwalk VP1 Vaccine, Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with double-stranded RNA Adjuvant

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

* To be eligible for this study, participants must meet all the following: Age 1. 18 to 55 years old inclusive at the time of signing the Informed Consent Form (ICF). Type of Participants 2. General good health, without significant uncontrolled medical illness, based on medical history, physical examination, vital signs, and clinical laboratories (CBC, chemistry, and urinalysis) as determined by the investigator in consultation with the Research Monitor and Sponsor 3. Body mass index (BMI) between 17 and 35 kg/m2 at screening 4. Available for all planned visits and phone calls, and willing to complete all protocol- defined procedures and assessments (including ability and willingness to swallow multiple small enteric-coated tablets per study dose). Gender and Reproductive Considerations 5. Male or female participants Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Female participants must provide a negative pregnancy test at each required visit and fulfill one of the following criteria: * At least 1 year post-menopausal (defined as amenorrhea for ≥12 consecutive months prior to Screening without an alternative medical cause). * Women under 60 years will need to verify post-menopausal status via a follicle-stimulating hormone (FSH) test if another option to prevent potential pregnancy will not be utilized for 30 days prior to baseline vaccination and until 60 days after the last vaccination. * Surgically sterile * Use of oral, implantable, transdermal or injectable contraceptives for 30 days prior to initial vaccination and until 60 days after the last vaccination. The form of contraception must be approved by the Investigator * A reliable form of contraception must be approved by the Investigator (e.g., double barrier method, Depo-Provera, intrauterine device, Norplant, oral contraceptives, contraceptive patches). * Not be sexually active (abstinent) or be in a relationship with partner who is sterile (must be discussed with site staff and documented). Informed Consent 6. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion criteria

* The participants must be excluded from participating in the study if they meet any of the following: Medical Conditions 1. Presence of significant uncontrolled medical or psychiatric illness (acute or chronic) including institution of new medical/surgical treatment or significant dose alteration for uncontrolled symptoms or drug toxicity within 3 months of screening and reconfirmed at baseline 2. Cancer, or received treatment for cancer, within past 3 years (excluding basal cell carcinoma or squamous cell carcinoma) 3. Presence of immunosuppression or medical condition possibly associated with impaired immune responsiveness, including diabetes mellitus 1 and 2 4. History of irritable bowel disease or other inflammatory digestive or gastrointestinal condition that could affect the distribution/safety evaluation of an orally administered vaccine targeting the mucosa of the small intestine. Such conditions may include but are not limited to: 1. Esophageal Motility Disorder 2. Malignancy 3. Malabsorption 4. Pancreaticobiliary disorders 5. Irritable bowel syndrome 6. Inflammatory Bowel Disease 7. Surgical Resection 8. GERD 9. Hiatal Hernia 10. Peptic Ulcer (History of cholecystectomy is not exclusionary) 5. History of any form of angioedema 6. History of serious reactions to any vaccination such as anaphylaxis, respiratory problems, hives or abdominal pain 7. Diagnosed bleeding disorder or significant bruising or bleeding difficulties that could make blood draws problematic 8. Any condition that resulted in the absence or removal of the spleen 9. Acute disease within 72 hours prior to vaccination defined as the presence of a moderate or severe illness (as determined by the Investigator through medical history and physical exam). (Assessment may be repeated during screening period.) 10. Presence of a fever ≥ 38oC measured orally at baseline (Assessment may be repeated during screening period) 11. Any significant hospitalization within the last year which in the opinion of the Investigator or Sponsor could interfere with study participation. 12. Any other condition that in the clinical judgment of the investigator would jeopardize the safety or rights of a participant taking in the study, would render the participant unable to comply with the protocol or would interfere with the evaluation of the study endpoints Diagnostic Assessments 13. Positive human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) tests at the screening visit 14. Positive urine drug screen for drugs of abuse at screening 15. Positive breath or urine alcohol test at screening and baseline Prior/Concurrent Therapy 16. Receipt of a licensed vaccine within 14 days prior to baseline vaccination or planned administration during the study active period (4 weeks post each study vaccination). 17. Use of antibiotics, proton pump inhibitors, H2 blockers or antacids within 7 days prior to study drug administration or planned use during the active study period 18. Use of medications known to affect the immune function (e.g., systemic corticosteroids and others) within 2 weeks before study drug administration or planned use during the active study period 19. Daily use of nonsteroidal anti-inflammatory drugs within 7 days prior to study drug administration or planned use during the active study period 20. Administration of any investigational vaccine, drug or device within 8 weeks preceding study drug administration (Day 1), or planned use within the duration of the study Other Exclusions 21. Donation or use of blood or blood products within 30 days prior to study drug administration or planned donation during the active study period 22. History of drug, alcohol or chemical abuse within 1 year of screening 23. History of hypersensitivity or allergic reaction to any component of the investigational vaccine, including but not limited to fish gelatin

Design outcomes

Primary

Measure	Time frame	Description
Viral-capsid Protein 1 (VP1)-Specific Antibody Secreting Cells (ASC) by Enzyme-linked Immunospot (ELISpot) Assay	Day 1 (Initial Vaccination) through Day 8 post boost (Second Vaccination)	Comparison of VPI specific immunoglobin A (IgA) ASC levels between the 3 study cohorts by enzyme-linked immunospot (ELISpot) assay
Norovirus G1.1 Histo-blood Group Antigen (HBGA) Blocking Antibodies (BT50) Assay	Day 1 (Initial Vaccination) through Day 29 post boost (Second Vaccination)	Comparison of subjects with a ≥2-, 3- or 4-fold increase over baseline titer of GI.1 histo-blood group antigen (HBGA) blocking antibodies (BT50) levels between the 3 study cohorts.
VP1 Serum Immunoglobin G (IgG) by Mesoscale Discovery (MSD) Assay	Day 1 (Initial Vaccination) through Day 29 post boost (Second Vaccination)	Comparison of VPI specific immunoglobin A (IgA) ASC levels by Mesoscale Discovery (MSD) assay between the 3 study cohorts

Secondary

Measure	Time frame	Description
Solicited Symptoms of Reactogenicity	Day 1 (Vaccination) to Day 8 post each vaccination	Comparison of frequency, duration, and severity of solicited symptom events in participants

Other

Measure	Time frame	Description
Unsolicited Adverse Events (AEs)	Day 1 (Vaccine) through 28 days following boost (Second Vaccination)	Comparison of the frequency, duration, and severity of unsolicited AEs and serious AEs (SAEs) including AEs of Special Interest (AESIs) and new onsets of chronic illness (NOCIs) in participants
Long-term Safety	Day 1 (Vaccine) through 6 months following boost (Second Vaccination)	Frequency, duration, and severity of all SAEs, AESIs and NOCIs through 6 months after last vaccination.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Cohort 1 (4-week Boost Vaccination) (4-week boost vaccination) 10 subjects will receive two doses of 1x10 log10 IU ± 0.5 log at Day 1 and Week 4 VXA-G1.1-NN: Norovirus GI.1 Norwalk VP1 Vaccine, Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with double-stranded RNA Adjuvant	10
Cohort 2 (8-week Boost Vaccination) (8-week boost vaccination) 10 subjects will receive two doses of 1x10 log10 IU± 0.5 log at Day 1 and Week 8 VXA-G1.1-NN: Norovirus GI.1 Norwalk VP1 Vaccine, Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with double-stranded RNA Adjuvant	10
Cohort 3 (12-week Boost Vaccination) (12-week boost vaccination) 10 subjects will receive two doses of 1x10 log10 IU± 0.5 log at Day 1 and Week 12 VXA-G1.1-NN: Norovirus GI.1 Norwalk VP1 Vaccine, Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with double-stranded RNA Adjuvant	10
Total	30

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Lost to Follow-up	1	0	0

Baseline characteristics

Characteristic	Cohort 1 (4-week Boost Vaccination)	Cohort 2 (8-week Boost Vaccination)	Cohort 3 (12-week Boost Vaccination)	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	10 Participants	10 Participants	10 Participants	30 Participants
Age, Continuous	43.2 years STANDARD_DEVIATION 7.42	35.4 years STANDARD_DEVIATION 9.97	34.9 years STANDARD_DEVIATION 10.09	37.8 years STANDARD_DEVIATION 9.72
BMI	28.27 kg/m^2 STANDARD_DEVIATION 3.248	27.94 kg/m^2 STANDARD_DEVIATION 4.94	27.32 kg/m^2 STANDARD_DEVIATION 3.917	27.84 kg/m^2 STANDARD_DEVIATION 3.971
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	3 Participants	3 Participants	9 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants	7 Participants	7 Participants	21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Height	163.23 centimeter STANDARD_DEVIATION 7.236	175.63 centimeter STANDARD_DEVIATION 7.85	166.22 centimeter STANDARD_DEVIATION 10.734	168.36 centimeter STANDARD_DEVIATION 10.001
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	5 Participants	3 Participants	3 Participants	11 Participants
Race (NIH/OMB) Black or African American	2 Participants	2 Participants	0 Participants	4 Participants
Race (NIH/OMB) More than one race	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
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	3 Participants	5 Participants	7 Participants	15 Participants
Region of Enrollment United States	10 participants	10 participants	10 participants	30 participants
Sex: Female, Male Female	4 Participants	7 Participants	4 Participants	15 Participants
Sex: Female, Male Male	6 Participants	3 Participants	6 Participants	15 Participants
Vaccinated for COVID-19 No	2 Participants	4 Participants	7 Participants	13 Participants
Vaccinated for COVID-19 Yes - Johnson & Johnson	0 Participants	0 Participants	0 Participants	0 Participants
Vaccinated for COVID-19 Yes - Moderna	4 Participants	3 Participants	0 Participants	7 Participants
Vaccinated for COVID-19 Yes - Other	0 Participants	0 Participants	0 Participants	0 Participants
Vaccinated for COVID-19 Yes - Pfizer-BioNTech	4 Participants	3 Participants	3 Participants	10 Participants
Weight	75.22 kilogram STANDARD_DEVIATION 9.359	86.99 kilogram STANDARD_DEVIATION 20.457	75.54 kilogram STANDARD_DEVIATION 13.36	79.25 kilogram STANDARD_DEVIATION 15.603

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 10	0 / 10	0 / 10
other Total, other adverse events	6 / 10	3 / 10	6 / 10
serious Total, serious adverse events	0 / 10	1 / 10	0 / 10

Outcome results

Primary

Norovirus G1.1 Histo-blood Group Antigen (HBGA) Blocking Antibodies (BT50) Assay

Comparison of subjects with a ≥2-, 3- or 4-fold increase over baseline titer of GI.1 histo-blood group antigen (HBGA) blocking antibodies (BT50) levels between the 3 study cohorts.

Time frame: Day 1 (Initial Vaccination) through Day 29 post boost (Second Vaccination)