Clinical trial NCT05029856: Evaluation of the Safety and Immunogenicity of SII Vaccine Constructs Based on the SARS-CoV-2 (COVID-19) Variant in Adults
Official title: A Randomized, Observer-Blinded, Phase 1/2 Study With an Open-Label Group to Evaluate the Safety and Immunogenicity of SII Vaccine Constructs Based on SARS-CoV-2 Variants in Adults
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Covid19
Lead sponsor: Novavax
Sponsor class: INDUSTRY
First posted: 2021-09-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a randomized, observer-blinded, Phase 1/2 study with an open-label group to evaluate the safety and immunogenicity of 3 novel SARS-CoV-2 variant vaccine constructs adjuvanted with Matrix-M1 adjuvant. Investigational products will include a monovalent SII SARS-CoV-2 B.1.351 (Beta) variant vaccine (SII B.1.351), a bivalent SII vaccine containing antigen for both the ancestral strain and B.1.351 (Beta) variant of SARS-CoV-2 (SII Bivalent), and a monovalent SII SARS-CoV-2 B.1.617.2 (Delta) variant vaccine (SII B.1.617.2).


Eligibility criteria: Inclusion Criteria:

1. Adults 18 to 64 years of age, inclusive, at screening.
2. Willing and able to give informed consent prior to study enrollment and to comply with study procedures.
3. Female participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile \[ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy\] or postmenopausal \[defined as amenorrhea at least 12 consecutive months\]) must agree to be heterosexually inactive from at least 28 days prior to enrollment and through the end of the study OR agree to consistently use a medically acceptable method of contraception listed below from at least 28 days prior to enrollment and through the end of the study.

   1. Condoms (male or female) with spermicide (if acceptable in country)
   2. Diaphragm with spermicide
   3. Cervical cap with spermicide
   4. Intrauterine device
   5. Oral or patch contraceptives
   6. Norplant®, Depo-Provera®, or other in-country regulatory approved contraceptive method that is designed to protect against pregnancy
   7. Abstinence, as a form of contraception, is acceptable if in line with the participant's lifestyle
4. Is medically stable, as determined by the investigator (based on a review of health status, vital signs \[to include body temperature\], medical history, and targeted physical examination \[to include body weight\]). Vital signs must be within medically acceptable ranges prior to the first vaccination.
5. Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study.

   For previously vaccinated Participants (Groups C, D and H):
6. Documented receipt of 2 doses of the investigational Novavax vaccine with Matrix-M1 adjuvant (NVX-CoV2373) administered approximately 21 days apart or 2 doses of a TGA-authorized/approved COVID-19 vaccine administered at least 60 days prior to first study vaccination.

Exclusion Criteria:

If an individual meets any of the following criteria, he or she is ineligible for this study:

1. History of laboratory-confirmed (by PCR or serology to SARS-CoV-2) COVID-19 infection at any time prior to randomization/enrollment.
2. Previous receipt of any investigational or authorized/approved vaccine, prophylactic or therapeutic agent for the prevention or treatment of SARS-CoV-2 infection, except for previously vaccinated participants.
3. Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to first study vaccination.
4. Received influenza vaccination within 14 days prior to first study vaccination, or any other vaccine within 30 days prior to the first study vaccination.
5. Any known allergies to products contained in the investigational product.
6. Any history of anaphylaxis to any prior vaccine.
7. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.
8. Chronic administration (defined as \> 14 continuous days) of immunosuppressants, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to first study vaccination.
9. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to first study vaccination.
10. Active cancer (malignancy) on therapy within 3 years prior to first study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma or lentigo maligna and uterine cervical carcinoma in situ without evidence of disease, at the discretion of the investigator).
11. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of study.
12. Suspected or known history of alcohol abuse or drug addiction within 2 years prior to the first study vaccine dose that, in the opinion of the investigator, might interfere with protocol compliance.
13. Any other condition that, in the opinion of the investigator, would pose a health risk to the participant if enrolled or could interfere with evaluation of the study vaccine or interpretation of study results (including neurologic or psychiatric conditions likely to impair the quality of safety reporting).
14. Study team member or immediate family member of any study team member (inclusive of Sponsor, CRO, and study site personnel involved in the conduct or planning of the study).

Primary outcomes:
measure: MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as GMT
timeFrame: Day 14 and Day 35
measure: MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs
timeFrame: Day 14 and Day 35
measure: MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta)expressed as GMT
timeFrame: Day 14 and Day 35
measure: MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta)expressed as SCRs/SRRs
timeFrame: Day 14 and Day 35
measure: Incidence, duration, and severity of solicited local and systemic adverse events (AEs)
timeFrame: Day 0 to Day 7
measure: Incidence, duration, severity, and relationship of unsolicited AEs through 28 days
timeFrame: Day 0 to Day 28
measure: Incidence and relationship of medically attended adverse events (MAAEs), adverse events of special interest (AESIs) (predefined list), and serious adverse events (SAEs)
timeFrame: Day 0 to Day 217
Secondary outcomes:
measure: MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in previously vaccinated patients
timeFrame: Day 0 to Day 189
measure: MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in participants seronegative at baseline
timeFrame: Day 0 to Day 217
measure: MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs in previously vaccinated patients
timeFrame: Day 0 to Day 189
measure: MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs in participants seronegative at baseline.
timeFrame: Day 0 to Day 217
measure: MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta) expressed as GMFR in participants seronegative at baseline
timeFrame: Day 0 to Day 217
measure: MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta) expressed as GMFR in previously vaccinated participants
timeFrame: Day 0 to Day 189
measure: MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta)expressed as SCRs/ SRRs in participants seronegative at baseline
timeFrame: Day 0 to Day 217
measure: MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta)expressed as SCRs/ SRRs in previously vaccinated participants
timeFrame: Day 0 to Day 189
measure: IgG geometric mean concentrations (GMCs) to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in previously vaccinated participants
timeFrame: Day 0 to Day 189
measure: IgG geometric mean concentrations (GMCs) to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in participants seronegative at baseline
timeFrame: Day 0 to Day 217
measure: IgG geometric mean concentrations (GMCs) to the B.1.617.2 (Delta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein in participants seronegative at baseline
timeFrame: Day 0 to Day 217
measure: IgG geometric mean concentrations (GMCs) to the B.1.617.2 (Delta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein in previously vaccinated participants
timeFrame: Day 0 to Day 189
measure: Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in previously vaccinated participants
timeFrame: Day 0 to Day 189
measure: Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in participants seronegative at baseline
timeFrame: Day 0 to Day 217
measure: Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs in previously vaccinated participants
timeFrame: Day 0 to Day 189
measure: Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs in participants seronegative at baseline
timeFrame: Day 0 to Day 217
measure: Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.617.2 (Delta) expressed as GMFR in participants seronegative at baseline
timeFrame: Day 0 to Day 217
measure: Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.617.2 (Delta) expressed as GMFR in previously vaccinated participants
timeFrame: Day 0 to Day 189
measure: Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.617.2 (Delta) expressed as SCRs/SRRs in participants seronegative at baseline
timeFrame: Day 0 to Day 217
measure: Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.617.2 (Delta) expressed as SCRs/SRRs in previously vaccinated participants
timeFrame: Day 0 to Day 189
Other outcomes:
Locations:
city: Maroubra
country: Australia
facility: Australian Clinical Research Network (ACRN)
state: New South Wales
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice - Sydney
state: New South Wales
city: Geelong
country: Australia
facility: University Hospital Geelong-Barwon Health
state: Victoria
city: Melbourne
country: Australia
facility: Emeritus Research
state: Victoria
Study officials:
affiliation: Novavax
name: Clinical Development
role: STUDY_DIRECTOR
References: