Safety and Efficacy of Intranasal Administration of Avacc... | NCT05604690

Status Module

Name	Class
Novotech (Australia) Pty Limited	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment Arm: Cohort 1 and 2	Experimental	Subjects will receive 2 doses of Avacc 10 via intranasal application. Cohort 1 will receive a low dose of Avacc 10 Cohort 2 will receive a high dose of Avacc 10. Dosage Form: Liquid Unit Dose: Investigational product (IP) in Phosphate Buffered Saline Route of Administration: Intranasal Physical Description: Slightly opalescent in glass vial	Biological: Avacc 10
OMV Arm: Cohort 1 and 2	Active Comparator	Subjects will receive 2 doses of Outer Membrane Vesicles (OMV) comparator via intranasal application. Dosage Form: Liquid Unit Dose: OMV comparator in TRIS/sucrose buffer Route of Administration: Intranasal Physical Description: Slightly opalescent in glass vial	Combination Product: Outer Membrane Vesicles (OMV) : OMV alone in vehicle
Placebo Are: Cohort 1 and 2	Placebo Comparator	Subjects will receive 2 doses of placebo via intranasal application. Dosage Form: Liquid Unit Dose: Placebo in TRIS/sucrose buffer Route of Administration: Intranasal Physical Description: Clear, colorless in glass vial	Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Avacc 10	Biological	Intranasal application of either low dose or high dose of Covid 19 vaccine.	Treatment Arm: Cohort 1 and 2

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
To evaluate the safety and tolerability of intranasal administration of Avacc 10 in healthy subjects by incidence of adverse events.	Adverse Events will be coded using the most current version of the MedDRA®	Screening to end of the follow up period; up to 28 days post final administration period
To evaluate the safety and tolerability of intranasal administration of Avacc 10 in healthy subjects by evaluating serious adverse events.	Serious Adverse Events will be coded using the most current version of the MedDRA®	Screening to end of the follow up period; up to 28 days post final administration period
To evaluate the safety and tolerability of intranasal administration of Avacc 10 in healthy subjects by incidence of clinically significant laboratory findings	Clinical laboratory samples will consist of hematology, biochemistry, and urinalysis	Screening to end of the follow up period; up to 28 days post final administration period
To evaluate the safety and tolerability of intranasal administration of Avacc 10 in healthy subjects by incidence of clinically significant ECG findings	ECG findings will be used for safety analysis.	Screening to end of the follow up period; up to 28 days post final administration period
To evaluate the safety and tolerability of intranasal administration of Avacc 10 in healthy subjects by incidence of clinically significant vital signs	BP [systolic and diastolic], PR, and temperature will be measured for analysis of vital signs	Screening to end of the follow up period; up to 28 days post final administration period

Secondary Outcomes

Measure	Description	Time Frame
To evaluate the immunogenic response of intranasal administration of Avacc 10 in healthy subjects. Immunogenicity evaluations will be done via serum analysis for biomarkers representative of an immunogenic response to a SARSCoV-2 vaccine.	Assessment will be performed of the association between changes in immunogenicity outcomes of SARS-CoV-2 NAbs in serum, anti-SARS-CoV-2 IgA and IgG in serum. The Immunogenicity Population will be the primary population for immunogenicity endpoints.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

To be eligible for this study, a participant has to meet all of the following inclusion criteria:
1. Healthy male or female subjects between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, a full physical/neurological examination including vital signs (including systolic and diastolic BP, temperature, and PR), a 12-lead ECG, and clinical laboratory tests).
2. Participant must have received a vaccination against SARS-CoV-2 or have been exposed to SARS-CoV-2 at least ≥ 4 months prior to the first study dose or shown to be sero-positive to IgG by any of the serological tests marketed as EUA and authorized by the FDA.
3. Negative test for SARS-CoV-2 at first visit (Day 1) prior to dosing.
4. Females must be non-pregnant and non-lactating and must use an acceptable, highly effective contraception in the case of heterosexual intercourse.
5. Males must use highly effective contraception in the case of heterosexual intercourse.
6. BMI between 18.0 to 32.0 kg/m2 , inclusive; and a total body weight ≥ 50.0 kg for males and ≥ 45.0 kg for females.
7. Written or electronic informed consent from the patient prior to any study procedures in a manner approved by a HREC.
8. Willing and able to comply with the scheduled visits, confinement period, treatment plan, laboratory tests, and other trial procedures and requirements.

Exclusion Criteria:

A participant who meets any of the following exclusion criteria must be excluded from the study:
1. Evidence or history of medical conditions which are unstable, or under investigations currently, defined as major changes to management/medication or surgery/hospitalization in the last 12 months, including hematological (including clotting disorders), renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, and untreated seasonal allergies at time of dosing).
2. History of clinically significant autoimmune disorder (such as Guillain-Barré syndrome).
3. History of febrile illness within 14 days prior to the first dose.
4. Confirmed SARS-CoV-2 infection within the last 4 months prior to study enrollment.
5. Known exposure to another person with SARS-CoV-2 infection within the last 14 days prior to study enrolment.
6. Vaccination with a live vaccine within the 4 weeks prior to study enrollment or any non-live vaccination within the 2 weeks prior to study enrollment, or that is planned during study participation.
7. Vaccination against N. meningitidis (type B).
8. History of frequent epistaxis (defined as a weekly occurrence, or more frequently).
9. Evidence of a deviated septum, or other nasal abnormality, which may impede the ability for intranasal administration of any study medication.
10. History of, or current positive results for, any of the following serological tests: HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HbcAb), or hepatitis C antibody (HCVAb).
11. Malignancy or a history of malignancy in the previous 5 years, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or adequately treated cervical carcinoma-in-situ.
12. Documented history of alcohol, cocaine, or IV drug abused within 6 months of study enrollment.
13. Treatment with an IP within 90 days, preceding study enrollment.
14. Use of prescription and non-prescription intranasal drug within 7 days prior to first dose of intranasal administration and throughout the study, until 1 month after the last intranasal administration.
15. Screening supine BP ≥ 155 mmHg (systolic) or ≥ 95 mmHg (diastolic), following at least 5 minutes of supine rest. If BP is ≥ 155 mmHg (systolic) or ≥ 95 mmHg (diastolic), the BP should be repeated 2 more times with the subject at supine rest and the average of the 3 BP values should be used to determine the subjects' eligibility.
16. Screening 12-lead ECG following at least 5 minutes of supine rest demonstrating a Fridericia corrected QT (QTcF) interval ˃ 450 msec (for males) or > 470 msec (for females) or a QRS interval ≥ 120 msec. If QTcF exceeds 450 msec for men or 470 msec for females, or QRS exceeds ≥ 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF (or QRS) values should be used to determine the subjects' eligibility.
17. Subjects with clinically significant abnormalities (as determined by the Investigator) in clinical laboratory tests at Screening, as assessed by the study-specific clinical laboratory. A single repeat test may be conducted if deemed necessary. Exception may be granted at the discretion of the Investigator where no confounding factors are expected to impact the safety of the subjects or the integrity of the study
18. Pregnant, lactating, or planning to become pregnant (self or partner) at any time during the study, or 90 days after last intranasal administration.
19. Blood or plasma donation of approximately 500 mL or more within 90 days prior to the first intranasal administration.
20. Previous history of intolerance or hypersensitivity to any component of the IP formulation.
21. Subjects who have previously experienced a Grade 3 or higher AE to receipt of a SARS-CoV-2 vaccination.
22. Subjects who are investigational site staff members directly involved in the conduct of this study and their family members, site staff otherwise supervised by the Investigator, and participants who are employees of the Sponsor or are agents of the Sponsor.
23. Any other reason, criteria that may interfere with the interpretation of study results or, in the judgement of the Investigator, would make the subject inappropriate for entry into this study.

ID	Term
D011024	Pneumonia, Viral
D011014	Pneumonia
D012141	Respiratory Tract Infections
D007239	Infections