Norovirus Infections
Conditions
Keywords
Healthy participants, VXA-G1.1-NN, VXA-G2.4-NS
Brief summary
The primary objective of this study is to evaluate the safety and tolerability of an oral bivalent GI.1/GII.4 norovirus vaccine administration in healthy lactating female participants and to assess the short-term immunogenicity of oral bivalent GI.1/GII.4 norovirus vaccine administration in healthy lactating female participants and its association with the immunogenicity response in breastmilk.
Interventions
BIOLOGICALVXA-G1.1-NN
Oral tablets.
BIOLOGICALVXA-G2.4-NS
Oral tablets.
BIOLOGICALPlacebo Tablets
Oral tablets.
Sponsors
Vaxart
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Lactating females aged ≥ 18 years at the time of enrolment and their breastfed infants aged \>30 days to 11 months of age at the time of the participants' study drug administration. 2. In stable and good general health, without significant medical illness, based on medical history, physical examination (including vital signs), and clinical judgment of the investigator. 3. Lactating females willing and able to provide informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. 4. Lactating females who are willing to provide consent for their breastfed infant. 5. Negative pregnancy tests at screening and prior to dose on Day 1. 6. Available for all planned visits and tele-health appointments, and ability to comply with all study-related evaluations (including but not limited to having the ability and willingness to swallow multiple small enteric-coated tablets per study dose, express/pump breastmilk, and collect infant stool samples). 7. Plan to continue breastfeeding as the main source of the infant's nutrition for at least 1 month (longer is preferred with goal of 6 months post dose if possible) from the time of study drug administration. Exclusive breastfeeding is acceptable but not necessary. 8. The nursing infant is the product of a singleton pregnancy AND does not have any of the following: 1. Any abnormality that may interfere with breastfeeding or milk absorption 2. Active infection (may be included if the infection resolves and the participant is re-assessed during the screening period) 3. Infant has any other medical condition or abnormality that, in the opinion of the investigator, could compromise the infant's appropriate inclusion in this study including interference with the interpretation of study results (such as malabsorption) 4. One or more documented brief resolved unexplained events (BRUEs) 5. Extreme prematurity (infants who were born at less than 28 weeks gestation) 6. 30 days of age or less at the participant's study drug administration OR greater than 11 months of age at the participant's study drug administration 7. Prior hospitalization that is not exclusively for hyperbilirubinemia requiring phototherapy 8. Any genetic/metabolic disease 9. Any chronic illness requiring long term medication 9. Participants must be willing to use a highly effective form of contraception for 30 days prior to vaccination and until 60 days after the vaccination. Acceptable forms are oral, implantable, intrauterine, transdermal, intravaginal, injectable, double barrier or abstinence (participants using diaphragms must also use condom). The form of contraception must be approved by the investigator.
Exclusion criteria
1. Presence of a fever ≥ 38.0°C measured orally at baseline, on Day 1 prior to vaccination. (Assessment may be repeated once during screening period). 2. 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 once during screening period). 3. Participants who have received antipyretic/analgesic medications within 24 hours prior to the intended vaccine administration. 4. Positive human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) tests at the screening visit. 5. History of hypersensitivity or allergic reaction to any component of the investigational vaccine, including but not limited to fish gelatin. 6. History of serious reactions to vaccination such as anaphylaxis, respiratory problems, hives, or abdominal pain. 7. Presence of significant uncontrolled medical or psychiatric illness (acute or chronic) including the 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. 8. History of significant pregnancy-related complications during this pregnancy, including but not limited to pre-eclampsia, eclampsia, or gestational diabetes unless a full resolution is documented. 9. Cancer, or treatment for cancer, within the past 3 years (excluding fully treated and resolved basal cell carcinoma or squamous cell carcinoma). 10. Presence of immunosuppression or medical condition possibly associated with impaired immune responsiveness, including diabetes mellitus type 1 or 2. 11. 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: a. Any history of: i. Malignancy ii. Malabsorption iii. Pancreatobiliary disorders iv. Inflammatory bowel disease v. Irritable bowel disease vi. Hiatal hernia vii. Surgical resection b. History of diagnosis or treatment in past 5 years of: i. Esophageal or gastric motility disorder ii. Gastroesophageal reflux disease (GERD) - Will allow for participants with a history of pregnancy-related GERD if fully resolved for \>3 months and no other history of GERD diagnosis iii. Peptic ulcer iv. Cholecystectomy 12. Any condition that resulted in the absence or removal of the spleen. 13. History of any form of angioedema. 14. Diagnosed bleeding disorder or significant bruising or bleeding difficulties that could make blood draws problematic. 15. History of GI bleeding including hematochezia (blood in stool) or melena (black stool). 16. Any significant hospitalization within the last year which in the opinion of the investigator or sponsor could interfere with study participation. 17. Any of the following history or conditions that may lead to a higher risk of clotting events and/or thrombocytopenia: 1. Family or personal history of bleeding or thrombosis 2. History of heparin-related thrombotic events, and/or receiving heparin treatments 3. History of autoimmune or inflammatory disease 4. Presence of any of the following conditions known to increase the risk of thrombosis within 6 months prior to screening: i. Recent surgery other than fully healed cesarean delivery or excision/ biopsy of cutaneous lesions ii. Immobility (confined to bed or wheelchair for 3 or more successive days) iii. Head trauma with loss of consciousness or documented brain injury iv. Receipt of anticoagulants for prophylaxis of thrombosis v. Recent clinically significant infection including hospitalization for COVID-19 related illness 18. 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. 19. Receipt of a licensed vaccine (including any COVID-19 vaccines under Emergency Use Authorization) within 14 days prior to study drug dose or planned administration during the study active period. 20. 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. 21. Use of medications known to affect the immune function (including but not limited to systemic corticosteroids, leukotriene modifiers, and Janus kinase \[JAK\] inhibitors) within 2 weeks before study drug administration or planned use during the active study period. 22. Daily use of nonsteroidal anti-inflammatory drugs within 7 days prior to study drug administration or planned use during the active study period. 23. Donation or receipt of blood or blood products within 30 days prior to study drug administration or planned donation during the active study period. 24. Participating in any clinical trial with another investigational product within 30 days prior to the first trial visit or intend to participate in another clinical trial at any time during the conduct of this trial. 25. Are first-degree relatives of individuals involved in trial conduct. 26. Positive urine drug screen for drugs of abuse at screening. 27. Positive alcohol test at screening or baseline. 28. History of drug, alcohol, or chemical abuse within 1 year of screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants (Mothers) With Any Solicited Symptoms of Reactogenicity for 1 Week Following Trial Dose | 1 week post study dose (8 days) | Solicited symptoms of reactogenicity were predefined adverse events (AEs) for which the participant was specifically questioned, and which were noted by the participant in their solicited symptom diary, including: fever (any temperature 100°F or higher), headache, myalgia (muscle pain), abdominal pain, anorexia (defined as not eating), nausea, vomiting, diarrhea, and malaise/fatigue. The severity of each solicited symptom of reactogenicity was graded by the participant as mild, moderate, severe or life-threatening. |
| Number of Participants (Mothers) With Unsolicited Treatment-emergent Adverse Events (TEAEs) | 4 weeks post dose (29 days) | TEAEs:AEs that began after start of an investigational product or an already present event that worsens in intensity or frequency following intervention.An AE considered serious (SAE) if,in view of Investigator or Sponsor,it resulted in death,life-threatening AE,inpatient hospitalization/prolongation of hospitalization,persistent or significant incapacity or disability disrupting normal life functions,congenital anomaly/birth defect,or an important medical event which based upon medical judgment may have jeopardized participant and required intervention to prevent 1 of outcomes.AESIs:serious/non-serious AEs of scientific and medical concern with potential immune mediated conditions and events associated with thrombosis and thrombocytopenia.NOCI:diagnosis post-enrollment and vaccination of new chronic medical condition,including those controllable by medication.An AE was unsolicited if it did not fulfill conditions prelisted in eCRF in terms of diagnosis/onset window post-vaccination. |
| Geometric Mean Concentration (GMC) of Serum Viral Protein 1 (VP1) Specific (G1.1) Immunoglobulin A (IgA) on Days 1, 8 and 29 | Days 1, 8 and 29 | GMC of serum VP1 specific (G1.1) IgA was measured by Meso Scale Discovery (MSD) assay. Assay was measured in an arbitrary unit per milliliter (AU/mL). |
| GMC of Serum VP1 Specific (G2.4) IgA on Days 1, 8 and 29 | Days 1, 8 and 29 | GMC of serum VP1 specific (G2.4) IgA was measured by MSD assay. Assay is measured in AU/mL. |
| Geometric Mean Fold Rise (GMFR) From Day 1 to Day 8 of Serum VP1 Specific (G1.1) IgA From Day 1 to Day 8 | Day 1 to Day 8 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 8 with least square mean value at baseline (Day 1). |
| GMFR of Serum VP1 Specific (G1.1) IgA From Day 1 to Day 29 | Day 1 to Day 29 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 29 with least square mean value at baseline (Day 1). |
| GMFR of Serum VP1 Specific (G2.4) IgA From Day 1 to Day 8 | Day 1 to Day 8 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 8 with least square mean value at baseline (Day 1). |
| GMFR of Serum VP1 Specific (G2.4) IgA From Day 1 to Day 29 | Day 1 to Day 29 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 29 with least square mean value at baseline (Day 1). |
| Number of Participants Who Achieved a 2-fold, 3-fold and 4-fold GMC Rise in Serum VP1 Specific (G1.1) IgA | Days 1, 8, 29 and 180 | A 2, 3, 4-fold rise represented the participants with at least a 2, 3, or 4-fold rise in antibodies compared to pre-vaccination dosing Baseline (Day 1). |
| Number of Participants Who Achieve a 2-fold, 3-fold and 4-fold GMC Rise in Serum VP1 Specific (G2.4) IgA | Days 1, 8, 29 and 180 | A 2, 3, 4-fold rise represented the participants with at least a 2, 3, or 4-fold rise in antibodies compared to pre-vaccination dosing Baseline (Day 1). |
| GMC of Breastmilk VP1 Specific (G1.1) IgA on Days 1, 8 and 29 | Days 1, 8, and 29 | GMC of breastmilk VP1 specific (G1.1) IgA was measured by MSD assay. Assay is measured in Relative Light Unit per microgram (RLU)/µg of total IgA which is a normalized measure used to quantify the specific binding of IgA antibodies to norovirus VLPs (measured in RLU) relative to the total amount of IgA protein present in a breast milk. |
| GMC of Breastmilk VP1 Specific (G2.4) IgA on Days 1, 8 and 29 | Days 1, 8 and 29 | GMC of breastmilk VP1 specific (G2.4) IgA was measured by MSD assay. Assay is measured in RLU/µg of total IgA which is a normalized measure used to quantify the specific binding of IgA antibodies to norovirus VLPs (measured in RLU) relative to the total amount of IgA protein present in a breast milk. |
| GMFR of Breastmilk VP1 Specific (G1.1) IgA From Day 1 to Day 8 | Day 1 to Day 8 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 8 with least square mean value at baseline (Day 1). |
| GMFR of Breastmilk VP1 Specific (G2.4) IgA From Day 1 to Day 8 | Day 1 to Day 8 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 8 with least square mean value at baseline (Day 1). |
| GMFR of Breastmilk VP1 Specific (G1.1) IgA From Day 1 to Day 29 | Day 1 to Day 29 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 29 with least square mean value at baseline (Day 1). |
| GMFR of Breastmilk VP1 Specific (G2.4) IgA From Day 1 to Day 29 | Day 1 to Day 29 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 29 with least square mean value at baseline (Day 1). |
| Number of Participants Who Achieve a 2-fold, 3-fold and 4-fold GMC Rise in Breastmilk VP1 Specific (G1.1) IgA | Days 1, 8, 29, 60 and 180 | A 2, 3, and 4-fold rise represented the participants with at least a 2, 3, or 4-fold rise in antibody compared to pre-vaccination dosing Baseline (Day 1). |
| Number of Participants Who Achieve a 2-fold, 3-fold and 4-fold GMC Rise in Breastmilk VP1 Specific (G2.4) IgA | Days 1, 8, 29, 60 and 180 | A 2, 3, and 4-fold rise represented the participants with at least a 2, 3, or 4-fold rise in antibodies compared to pre-vaccination dosing Baseline (Day 1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With SAEs, AESIs and NOCIs Through 12 Months Post Dose | Up to 12 months | An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the eCRF in terms of diagnosis and/or onset window post-vaccination. An AESIs serious or nonserious) is one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor can be appropriate. NOCIs was defined as diagnosis post-enrollment and vaccination of a new medical condition, which is chronic in nature, including those potentially controllable by medication. Only unsolicited SAEs, AESI and NOCIs data was planned to be collected and assessed for the assessment of this OM and solicited SAEs, AESIs and NOCIs was out of the scope of assessment. Participants with unsolicited SAEs, AESIs and NOCIs throughout the trial were reported in this outcome measure. |
| GMC of Serum VP1 Specific (G1.1) IgA on Day 180 | Day 180 | GMC of serum VP1 specific (G1.1) IgA was measured by MSD assay. Assay is measured in AU/mL. |
| GMC of Serum VP1 Specific (G2.4) IgA on Day 180 | Day 180 | GMC of serum VP1 specific (G2.4) IgA was measured by MSD assay. Assay is measured in AU/mL. |
| GMFR of Serum VP1 Specific (G1.1) IgA From Day 1 to Day 180 | Day 1 to Day 180 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 180 with least square mean value at baseline (Day 1). |
| GMFR of Serum VP1 Specific (G2.4) IgA From Day 1 to Day 180 | Day 1 to Day 180 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 180 with least square mean value at baseline (Day 1). |
| GMC of Breastmilk VP1 Specific (G1.1) IgA on Days 60 and 180 | Days 60 and 180 | GMC of breastmilkVP1 specific (G1.1) IgA was measured by MSD assay. Assay is measured in RLU/µg of total IgA which is a normalized measure used to quantify the specific binding of IgA antibodies to norovirus VLPs (measured in RLU) relative to the total amount of IgA protein present in a breast milk. |
| GMC of Breastmilk VP1 Specific (G2.4) IgA on Days 60 and 180 | Days 60 and 180 | GMC of breastmilk VP1 specific (G2.4) IgA was measured by MSD assay. Assay is measured in RLU/µg of total IgA which is a normalized measure used to quantify the specific binding of IgA antibodies to norovirus VLPs (measured in RLU) relative to the total amount of IgA protein present in a breast milk. |
| GMFR of Breastmilk VP1 Specific (G1.1) IgA From Day 1 to Day 60 | Day 1 to Day 60 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 60 with least square mean value at baseline (Day 1). |
| GMFR of Breastmilk VP1 Specific (G2.4) IgA From Day 1 to Day 60 | Day 1 to Day 60 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 60 with least square mean value at baseline (Day 1). |
| GMFR of Breastmilk VP1 Specific (G1.1) IgA From Day 1 to Day 180 | Day 1 to Day 180 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 180 with least square mean value at baseline (Day 1). |
| GMFR of Breastmilk VP1 Specific (G2.4) IgA From Day 1 to Day 180 | Day 1 to Day 180 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 180 with least square mean value at baseline (Day 1). |
| GMC of Serum VP1 Specific (G1.1) Immunoglobulin G (IgG) on Days 1, 8, 29, and 180 | Days 1, 8, 29, and 180 | GMC of serum VP1 specific (G1.1) IgG was measured by MSD assay. Assay is measured in AU/mL. |
| GMC of Serum VP1 Specific (G2.4) IgG on Days 1, 8, 29, and 180 | Days 1, 8, 29 and 180 | GMC of serum VP1 specific (G2.4) IgG was measured by MSD assay. Assay is measured in AU/mL. |
| GMFR of Serum VP1 Specific (G1.1) IgG From Day 1 to Days 8, 29, and 180 | From Day 1 to Days 8, 29, and 180 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Days 8, 29 and 180 with least square mean value at baseline (Day 1). |
| GMFR of Serum VP1 Specific (G2.4) IgG From Day 1 to Days 8, 29, and 180 | From Day 1 to Days 8, 29, and 180 | GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Days 8, 29 and 180 with least square mean value at baseline (Day 1). |
| Number of Participants Who Achieved a 2-fold, 3-fold, and 4-fold GMC Rise in Serum VP1 Specific (G1.1) IgG | Days 1, 8, 29, and 180 | A 2, 3, and 4-fold rise represents the participants with at least a 2, 3, or 4-fold rise in antibodies compared to pre-vaccination dosing Baseline (Day 1). |
| Number of Participants Who Achieved a 2-fold, 3-fold and 4-fold GMC Rise in Serum VP1 Specific (G2.4) IgG | Days 1, 8, 29, and 180 | A 2, 3, and 4-fold rise represented the participants with at least a 2, 3, or 4-fold rise in antibodies compared to pre-vaccination dosing Baseline (Day 1). |
| Geometric Mean Titer (GMT) of Serum Blocking Titers 50 (BT50) (G1.1) on Days 1, 8, 29, and 180 | Days 1, 8, 29, and 180 | Serum BT50 (G1.1) through 6 months after trial drug dose was measured by histo-blood group antigen (HBGA) assay. Blood samples were collected at different timepoints throughout the trial. |
| GMT of Serum BT50 (G2.4) on Days 1, 8, 29, and 180 | Days 1, 8, 29, and 180 | Serum BT50 (G2.4) through 6 months after trial drug dose was measured by HBGA assay. Blood samples were collected at different timepoints throughout the trial. |
| GMFR of Serum BT50 (G1.1) From Day 1 to Days 8, 29 and 180 | Day 1 to Days 8, 29, and 180 | The fold rise was calculated per participant by dividing the least square mean value on Days 8, 29 and 180 with least square mean value at baseline (Day 1). |
| GMFR of Serum BT50 (G2.4) From Day 1 to Days 8, 29 and 180 | Day 1 to Days 8, 29 and 180 | The fold rise was calculated per participant by dividing the least square mean value on Days 8, 29 and 180 with least square mean value at baseline (Day 1). |
| Number of Participants Who Achieved 2-fold, 3-fold, and 4-fold GMT Rise in Serum VP1 Specific (G1.1) IgG | Days 1, 8, 29, and 180 | A 2, 3, and 4-fold rise represented the participants with at least a 2, 3, or 4-fold rise in antibodies compared to pre-vaccination dosing Baseline (Day 1). |
| Number of Participants With 2-fold, 3-fold and 4-fold GMT Rise in Serum VP1 Specific IgG (G2.4) | Days 1, 8, 29, and 180 | A 2, 3, and 4-fold rise represented the participants with at least a 2, 3, or 4-fold rise in antibodies compared to pre-vaccination dosing Baseline (Day 1). |
Countries
South Africa
Contacts
STUDY_DIRECTORMedical Director
Vaxart, Inc.
Participant flow
Recruitment details
A total of 76 mother participants were enrolled between October 2023 and December 2024 in South Africa.
Pre-assignment details
This study enrolled breastfeeding mother-infant dyads. Each dyad consisted of one lactating mother and her breastfed infant. Only mothers received the investigational product; infants did not receive any study treatment. All Participant Flow numbers (Started, Completed, Not Completed) represent mother-infant dyads.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized 18-65 years | 0 Participants |
| Age, Customized 30 days to 11 months | 76 Participants |
| Race/Ethnicity, Customized Ethnicity Black or African American | 29 Participants |
| Race/Ethnicity, Customized Ethnicity Others | 1 Participants |
| Race/Ethnicity, Customized Race | 152 Participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 10 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 | 0 / 16 | 0 / 30 | 0 / 30 | 0 / 16 |
| other Total, other adverse events | 16 / 30 | 13 / 30 | 6 / 16 | 0 / 30 | 0 / 30 | 0 / 16 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 16 | 0 / 30 | 0 / 30 | 0 / 16 |
Outcome results
None listed