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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04368988




Registration number
NCT04368988
Ethics application status
Date submitted
24/04/2020
Date registered
30/04/2020
Date last updated
9/10/2020

Titles & IDs
Public title
Evaluation of the Safety and Immunogenicity of a SARS-CoV-2 rS Nanoparticle Vaccine With/Without Matrix-M Adjuvant
Scientific title
A 2-Part, Phase 1/2, Randomized, Observer-Blinded Study To Evaluate The Safety And Immunogenicity Of A SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Or Without MATRIX-M™ Adjuvant In Healthy Subjects
Secondary ID [1] 0 0
2019nCoV-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - SARS-CoV-2 rS - Phase 1
Other interventions - SARS-CoV-2 rS/Matrix-M Adjuvant - Phase 1
Other interventions - Normal saline solution (NSS), Placebo - Phase 1
Other interventions - Normal saline solution (NSS), Placebo - Phase 2
Other interventions - SARS-CoV-2 rS/Matrix-M Adjuvant, Day 0 - Phase 1
Other interventions - Normal saline solution (NSS), Placebo, Day 21 - Phase 1
Other interventions - SARS-CoV-2 rS/Matrix-M Adjuvant, Days 0 and 21 - Phase 2
Other interventions - Normal saline solution (NSS), Placebo, Day 189 - Phase 2
Other interventions - SARS-CoV-2 rS/Matrix-M Adjuvant, Day 0 - Phase 2
Other interventions - Normal saline solution (NSS), Placebo, Day 21 - Phase 2
Other interventions - SARS-CoV-2 rS/Matrix-M Adjuvant - Day 189 - Phase 2

Placebo Comparator: Placebo - Phase 1 - 2 doses of Placebo (Saline), 1 dose each on Days 0 and 21.

Experimental: SARS-CoV-2 rS - 25 µg without Matrix-M - Phase 1 - 2 doses of SARS-CoV-2 rS - 25 µg, 1 dose each on Days 0 and 21.

Experimental: SARS-CoV-2 rS - 5 µg + 50 µg Matrix-M - Phase 1 - 2 doses of SARS-CoV-2 rS - 5 µg + 50 µg Matrix-M (mixed together for each injection), 1 dose each on Days 0 and 21.

Experimental: SARS-CoV-2 rS - 25 µg + 50 µg Matrix-M - Phase 1 - 2 doses of SARS-CoV-2 rS - 25 µg + 50 µg Matrix-M (mixed together for each injection), 1 dose each on Days 0 and 21.

Experimental: SARS-CoV-2 rS - 25 µg + 50 µg Matrix-M then Placebo - Phase 1 - 1 dose of SARS-CoV-2 rS - 25 µg + 50 µg Matrix-M (mixed together for injection), on Day 0 followed by 1 dose of Placebo on Day 21.

Placebo Comparator: Placebo - Phase 2 - 3 doses of Placebo (Saline), 1 dose each on Days 0, 21, and 189.

Experimental: SARS-CoV-2 rS - 5/5 µg + 50 µg Matrix-M - Phase 2 - 2 doses of SARS-CoV-2 rS - 5 µg + 50 µg Matrix-M (co-formulated), 1 dose each on Days 0 and 21, followed by 1 dose of Placebo on Day 189.

Experimental: SARS-CoV-2 rS - Alternating 5 µg + 50 µg Matrix-M - Phase 2 - 1 dose of SARS-CoV-2 rS - 5 µg + 50 µg Matrix-M (co-formulated) on Day 0 then 1 dose of Placebo on Day 21 followed by 1 dose of SARS-CoV-2 rS - 5 µg + 50 µg Matrix-M (co-formulated) on Day 189.

Experimental: SARS-CoV-2 rS - 25/25 µg + 50 µg Matrix-M - Phase 2 - 2 doses of SARS-CoV-2 rS - 25 µg + 50 µg Matrix-M (co-formulated), 1 dose each on Days 0 and 21, followed by 1 dose of Placebo on Day 189.

Experimental: SARS-CoV-2 rS - Alternating 25/5 µg + 50 µg Matrix-M - Phase 2 - 1 dose of SARS-CoV-2 rS - 25 µg + 50 µg Matrix-M (co-formulated) on Day 0 then 1 dose of Placebo on Day 21 followed by 1 dose of SARS-CoV-2 rS - 5 µg + 50 µg Matrix-M (co-formulated) on Day 189.


Other interventions: SARS-CoV-2 rS - Phase 1
Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS (0.6 mL) on Days 0 and 21.

Other interventions: SARS-CoV-2 rS/Matrix-M Adjuvant - Phase 1
Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS mixed with Matrix-M adjuvant (0.6 mL) on Days 0 and 21.

Other interventions: Normal saline solution (NSS), Placebo - Phase 1
Alternating intramuscular (deltoid) injections of placebo (0.6 mL) on Days 0 and 21.

Other interventions: Normal saline solution (NSS), Placebo - Phase 2
Alternating intramuscular (deltoid) injections of placebo (0.5 mL) on Days 0, 21, and 189.

Other interventions: SARS-CoV-2 rS/Matrix-M Adjuvant, Day 0 - Phase 1
Intramuscular (deltoid) injection of SARS-CoV-2 rS mixed with Matrix-M adjuvant (0.6 mL) on Day 0.

Other interventions: Normal saline solution (NSS), Placebo, Day 21 - Phase 1
Intramuscular injection of placebo (0.6 mL) in alternate deltoid on Day 21.

Other interventions: SARS-CoV-2 rS/Matrix-M Adjuvant, Days 0 and 21 - Phase 2
Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M adjuvant (0.5 mL) on Days 0 and 21.

Other interventions: Normal saline solution (NSS), Placebo, Day 189 - Phase 2
Intramuscular injection of placebo (0.5 mL) in alternating deltoid on Day 189.

Other interventions: SARS-CoV-2 rS/Matrix-M Adjuvant, Day 0 - Phase 2
Intramuscular (deltoid) injection of SARS-CoV-2 rS co-formulated with Matrix-M adjuvant (0.5 mL) on Day 0.

Other interventions: Normal saline solution (NSS), Placebo, Day 21 - Phase 2
Intramuscular injection of placebo (0.5 mL) in alternating deltoid on Day 21.

Other interventions: SARS-CoV-2 rS/Matrix-M Adjuvant - Day 189 - Phase 2
Intramuscular injection of SARS-CoV-2 rS co-formulated with Matrix-M adjuvant (0.5 mL) in alternating deltoid on Day 189.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Participants with Solicited Adverse Events (AEs) - Phase 1 - Percentage of participants with solicited AEs (local, systemic) for 7 days following each primary vaccination (Days 0, 21) by severity score, duration, and peak intensity.
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Safety Laboratory Values (Serum Chemistry, Hematology) - Phase 1 - Safety laboratory values (serum chemistry, hematology) by FDA toxicity scoring (absolute and change from baseline where identified) at 7 days after each vaccination.
Timepoint [2] 0 0
28 days
Primary outcome [3] 0 0
Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs) - Phase 1 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by enzyme-linked immunosorbent assay (ELISA) expressed as GMTs through Day 35.
Timepoint [3] 0 0
35 days
Primary outcome [4] 0 0
Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs) - Phase 1 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs through Day 35.
Timepoint [4] 0 0
35 days
Primary outcome [5] 0 0
Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs) - Phase 1 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs through Day 35. SCR is the proportion of participants with =4-fold rises in ELISA units.
Timepoint [5] 0 0
35 days
Primary outcome [6] 0 0
Serum IgG Antibody Levels Expressed as GMTs - Phase 2 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs for the two-dose regimens by dose at Day 35 regardless of baseline immune status and stratified by baseline immune status.
Timepoint [6] 0 0
Day 35
Primary outcome [7] 0 0
Serum IgG Antibody Levels Expressed as GMFRs - Phase 2 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs for the two-dose regimens by dose at Day 35 regardless of baseline immune status and stratified by baseline immune status.
Timepoint [7] 0 0
Day 35
Primary outcome [8] 0 0
Serum IgG Antibody Levels Expressed as SCRs - Phase 2 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs (=4-fold rises) for the two-dose regimens by dose at Day 35 regardless of baseline immune status and stratified by baseline immune status.
Timepoint [8] 0 0
Day 35
Primary outcome [9] 0 0
Participants with Solicited Adverse Events (AEs) - Phase 2 - Percentage of participants with solicited AEs (local, systemic) for 7 days following each primary vaccination (Days 0 and 21) by severity score, duration, and peak intensity. Unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, all medically attended adverse events [MAAEs]) through the 35 days by Medical Dictionary for Regulatory Activities (MedDRA) classification, severity score, and relatedness.
Timepoint [9] 0 0
28 days
Primary outcome [10] 0 0
Participants with Unsolicited AEs - Phase 2 - Percentage of participants with unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, all medically attended adverse events [MAAEs]) through the 35 days by Medical Dictionary of Regulatory Activities (MedDRA) classification, severity score, and relatedness.
Timepoint [10] 0 0
35 days
Secondary outcome [1] 0 0
Participants with Unsolicited AEs - Phase 1 - Percentage of participants with unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, all MAAEs) through the first 49 days by MedDRA classification, severity score, and relatedness.
Timepoint [1] 0 0
49 days
Secondary outcome [2] 0 0
Participants with Abnormal Vital Signs - Phase 1 - Percentage of participants with vital sign abnormalities on the day of vaccination by severity scoring immediately following vaccination.
Timepoint [2] 0 0
21 days
Secondary outcome [3] 0 0
Changes from Baseline in Body Temperature - Phase 1 - Mean changes from baseline in body temperature by treatment group and visit.
Timepoint [3] 0 0
189 days
Secondary outcome [4] 0 0
Changes from Baseline in Blood Pressure - Phase 1 - Mean changes from baseline in blood pressure by treatment group and visit.
Timepoint [4] 0 0
189 days
Secondary outcome [5] 0 0
Changes from Baseline in Pulse Rate - Phase 1 - Mean changes from baseline in pulse rate by treatment group and visit.
Timepoint [5] 0 0
189 days
Secondary outcome [6] 0 0
Participants with MAAEs - Phase 1 - Percentage of participants with MAAEs, defined as AEs that lead to an unscheduled visit to a healthcare practitioner, through Day 105 by MedDRA classification, severity score, and relatedness.
Timepoint [6] 0 0
105 days
Secondary outcome [7] 0 0
Participants with Related MAAEs; Serious Adverse Events (SAEs); and Adverse Events of Special Interest (AESI) - Phase 1 - Percentage of participants with MAAEs assessed as related to study vaccine, SAEs, and AESIs until the end of the study (EOS) by MedDRA classification and severity score. All SAEs and AESI, defined as potential immune-mediated medical conditions or AEs relevant to COVID-19, by MedDRA classification, severity score, and relatedness.
Timepoint [7] 0 0
386 days
Secondary outcome [8] 0 0
Assessment of Serum IgG Antibody Levels Expressed as GMTs at Multiple Time Points - Phase 1 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at multiple time points through Day 189.
Timepoint [8] 0 0
189 days
Secondary outcome [9] 0 0
Assessment of Serum IgG Antibody Levels Expressed as GMFRs at Multiple Time Points - Phase 1 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at multiple time points through Day 189.
Timepoint [9] 0 0
189 days
Secondary outcome [10] 0 0
Assessment of Serum IgG Antibody Levels Expressed as SCRs at Multiple Time Points - Phase 1 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs (proportion of participants with =2-fold and =4-fold rises in antibody levels) at multiple time points through Day 189.
Timepoint [10] 0 0
189 days
Secondary outcome [11] 0 0
Assessment of Serum IgG Antibody Levels Expressed by Seroresponse Rates (SRRs) at Multiple Time Points - Phase 1 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SRRs (proportion of participants with rises in ELISA units exceeding the 95th percentile of placebo participants) at multiple time points through Day 189.
Timepoint [11] 0 0
189 days
Secondary outcome [12] 0 0
Angiotensin-Converting Enzyme 2 (ACE2) Receptor Binding Inhibition Assay Expressed as GMTs - Phase 1 - Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMTs at multiple time points through Day 189.
Timepoint [12] 0 0
189 days
Secondary outcome [13] 0 0
ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs - Phase 1 - Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMFRs at multiple time points through Day 189.
Timepoint [13] 0 0
189 days
Secondary outcome [14] 0 0
ACE2 Receptor Binding Inhibition Assay Expressed as SCRs - Phase 1 - Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SCRs at multiple time points through Day 189.
Timepoint [14] 0 0
189 days
Secondary outcome [15] 0 0
ACE2 Receptor Binding Inhibition Assay Expressed as SRRs - Phase 1 - Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SRRs at multiple time points through Day 189.
Timepoint [15] 0 0
189 days
Secondary outcome [16] 0 0
Neutralizing Antibody Activity Expressed as GMTs - Phase 1 - Neutralizing antibody activity as detected by microneutralization assay (MN) expressed as GMTs at multiple time points through Day 49.
Timepoint [16] 0 0
49 days
Secondary outcome [17] 0 0
Neutralizing Antibody Activity Expressed as GMFRs - Phase 1 - Neutralizing antibody activity as detected by MN expressed as GMFRs at multiple time points through Day 49.
Timepoint [17] 0 0
49 days
Secondary outcome [18] 0 0
Neutralizing Antibody Activity Expressed as SCRs - Phase 1 - Neutralizing antibody activity as detected by MN expressed as SCRs at multiple time points through Day 49.
Timepoint [18] 0 0
49 days
Secondary outcome [19] 0 0
Neutralizing Antibody Activity Expressed as SRRs - Phase 1 - Neutralizing antibody activity as detected by MN expressed as SRRs at multiple time points through Day 49.
Timepoint [19] 0 0
49 days
Secondary outcome [20] 0 0
Assessment of Cell-Mediated (T helper 1 [Th1]/T helper 2 [Th2]) Pathways - Phase 1 - Cell-mediated (Th1/Th2) pathways as measured by whole blood (flow cytometry) and/or in vitro peripheral blood mononuclear cell (PBMC) stimulation (eg, enzyme-linked immunospot [ELISpot], cytokine staining) with SARS-CoV-2 rS protein(s) through Day 28.
Timepoint [20] 0 0
28 days
Secondary outcome [21] 0 0
Assessment of Serum IgG Antibody Levels Expressed as GMTs - Phase 2 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs for the single-dose regimens compared to the two-dose regimens and to placebo through Day 35 regardless of baseline immune status and stratified by baseline immune status.
Timepoint [21] 0 0
35 days
Secondary outcome [22] 0 0
Assessment of Serum IgG Antibody Levels Expressed as GMFRs - Phase 2 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs for the single-dose regimens compared to the two-dose regimens and to placebo through Day 35 regardless of baseline immune status and stratified by baseline immune status.
Timepoint [22] 0 0
35 days
Secondary outcome [23] 0 0
Assessment of Serum IgG Antibody Levels Expressed as SCRs (= 4-fold change) - Phase 2 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs (= 4-fold change) for the single-dose regimens compared to the two-dose regimens and to placebo through Day 35 regardless of baseline immune status and stratified by baseline immune status.
Timepoint [23] 0 0
35 days
Secondary outcome [24] 0 0
Assessment of Serum IgG Antibody Levels Expressed as GMTs at Multiple Time Points - Phase 2 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at multiple time points through Day 217 for the single-dose regimens compared to the two-dose regimens and to placebo, stratified by baseline immune response.
Timepoint [24] 0 0
217 days
Secondary outcome [25] 0 0
Assessment of Serum IgG Antibody Levels Expressed as GMFRs at Multiple Time Points - Phase 2 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at multiple time points through Day 217 for the single-dose regimens compared to the two-dose regimens and to placebo, stratified by baseline immune response.
Timepoint [25] 0 0
217 days
Secondary outcome [26] 0 0
Assessment of Serum IgG Antibody Levels Expressed as SCRs (= 4-fold change) at Multiple Time Points - Phase 2 - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs (= 4-fold change) at multiple time points through Day 217 for the single-dose regimens compared to the two-dose regimens and to placebo, stratified by baseline immune response.
Timepoint [26] 0 0
217 days
Secondary outcome [27] 0 0
ACE2 Receptor Binding Inhibition Assay Expressed as GMTs - Phase 2 - Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMTs at multiple time points through Day 217 for the single-dose regimens compared to the two-dose regimens and to placebo.
Timepoint [27] 0 0
217 days
Secondary outcome [28] 0 0
ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs - Phase 2 - Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMFRs at multiple time points through Day 217 for the single-dose regimens compared to the two-dose regimens and to placebo.
Timepoint [28] 0 0
217 days
Secondary outcome [29] 0 0
ACE2 Receptor Binding Inhibition Assay Expressed as SCRs - Phase 2 - Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SCRs (= 4-fold change) at multiple time points through Day 217 for the single-dose regimens compared to the two-dose regimens and to placebo.
Timepoint [29] 0 0
217 days
Secondary outcome [30] 0 0
Neutralizing Antibody Activity Expressed as GMTs - Phase 2 - Neutralizing antibody activity as detected by MN expressed as GMTs at Days 35 and 217 relative to baseline in a subset of subjects by absolute titers and change from baseline.
Timepoint [30] 0 0
217 days
Secondary outcome [31] 0 0
Neutralizing Antibody Activity Expressed as GMFRs - Phase 2 - Neutralizing antibody activity as detected by MN expressed as GMFRs at Days 35 and 217 relative to baseline in a subset of subjects by absolute titers and change from baseline.
Timepoint [31] 0 0
217 days
Secondary outcome [32] 0 0
Neutralizing Antibody Activity Expressed as SCRs (= 4-fold change) - Phase 2 - Neutralizing antibody activity as detected by MN expressed as SCRs (= 4-fold change) at Days 35 and 217 relative to baseline in a subset of subjects by absolute titers and change from baseline.
Timepoint [32] 0 0
217 days
Secondary outcome [33] 0 0
Assessment of Serum IgG Antibody Levels Expressed as GMTs - Phase 2 Boost - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at Days 189 and 217 for boosting assessment with either placebo or active boost.
Timepoint [33] 0 0
217 days
Secondary outcome [34] 0 0
Assessment of Serum IgG Antibody Levels Expressed as GMFRs - Phase 2 Boost - Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Days 189 and 217 for boosting assessment with either placebo or active boost.
Timepoint [34] 0 0
217 days
Secondary outcome [35] 0 0
Participants with MAAEs - Phase 2 - All MAAEs, defined as AEs that lead to an unscheduled visit to a healthcare practitioner, through Day 217 by MedDRA classification, severity score, and relatedness.
Timepoint [35] 0 0
217 days
Secondary outcome [36] 0 0
Participants with Related MAAEs; SAEs; and AESIs - Phase 2 - Percentage of participants with MAAEs assessed as related to study vaccine, SAEs, and AESIs until the end of the study (EOS) by MedDRA classification and severity score. All SAEs and AESI, defined as potential immune-mediated medical conditions or AEs relevant to COVID-19, by MedDRA classification, severity score, and relatedness.
Timepoint [36] 0 0
357 days
Secondary outcome [37] 0 0
Participants with Abnormal Vital Signs - Phase 2 - Percentage of participants with vital sign abnormalities on the day of vaccination by severity scoring immediately following vaccination. Descriptive statistics (mean, standard deviation, change from baseline) by treatment group, by visit.
Timepoint [37] 0 0
21 days
Secondary outcome [38] 0 0
Changes from Baseline in Body Temperature - Phase 2 - Mean changes from baseline in body temperature by treatment group and visit.
Timepoint [38] 0 0
189 days
Secondary outcome [39] 0 0
Changes from Baseline in Blood Pressure - Phase 2 - Mean changes from baseline in blood pressure by treatment group and visit.
Timepoint [39] 0 0
189 days
Secondary outcome [40] 0 0
Changes from Baseline in Pulse Rate - Phase 2 - Mean changes from baseline in pulse rate by treatment group and visit.
Timepoint [40] 0 0
189 days
Secondary outcome [41] 0 0
Participants with SARS-CoV-2 Positivity - Phase 2 - Percentage of participants with SARS-CoV-2 positivity as diagnosed by qualitative polymerase chain reaction (PCR) following COVID-19 symptoms assessment from Day 28 through 6 months with severity classification, overall and by age strata (18-59, 60-84 years).
Timepoint [41] 0 0
161 days
Secondary outcome [42] 0 0
Assessment of SARS-CoV-2 by Qualitative PCR - Phase 2 - Assessment of SARS-CoV-2 by qualitative PCR based on routine screening by self- collection (nasal mid-turbinate or saliva) from Day 28 through 6 months without symptomatology to further describe epidemiologic evolution of the pandemic and potential effect of vaccination.
Timepoint [42] 0 0
161 days
Secondary outcome [43] 0 0
Assessment of Cell-Mediated (Th1/Th2) Pathways - Phase 2 - Assessment of cell-mediated (Th1/Th2) pathways as measured by whole blood (flow cytometry) and/or in vitro PBMC stimulation (eg, ELISpot, cytokine staining) with SARS-CoV-2 rS protein(s) through Day 28.
Timepoint [43] 0 0
28 days

Eligibility
Key inclusion criteria
Inclusion Criteria (Part 1):

- Healthy adult males or females between 18 and 59 years of age, inclusive, at
screening. Healthy status will be determined by the investigator based on medical
history, clinical laboratory results, vital sign measurements, and physical
examination at screening.

- The participant has a body mass index 17 to 35 kg/m2, inclusive, at screening.

- Willing and able to give informed consent prior to study enrollment and comply with
study procedures.

- Female participants of childbearing potential (defined as any female 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 or documented plasma follicle-stimulating hormone (FSH)
level =40 mIU/mL]) must agree to be heterosexually inactive from at least 21 days
prior to enrollment and through 6 months after the last vaccination OR agree to
consistently use any of the described methods of contraception from at least 21 days
prior to enrollment and through 6 months after the last vaccination.
Minimum age
18 Years
Maximum age
84 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria (Part 1):

- Any ongoing, symptomatic acute or chronic illness requiring medical or surgical care,
inclusive of changes in medication in the past 2 months indicating that chronic
illness/disease is not stable (at the discretion of the investigator). This includes
any current workup of undiagnosed illness that could lead to a new condition.

- Chronic disease inclusive of: a) hypertension uncontrolled for age according to the
Eighth Joint National Committee (JNC 8) guidelines; b) congestive heart failure by New
York Heart Association (NYHA) functional classification of greater or equal to II; c)
chronic obstructive pulmonary disease by Global Initiative for Obstructive Lung
Disease (GOLD) classification of greater or equal to 2; d) recent (within 6 months
prior to first study vaccination) exacerbation of coronary artery disease as
manifested by cardiac intervention, addition of new cardiac medications for control of
symptoms, or unstable angina; e) asthma (diagnosed by spirometry showing reversibility
of disease and must meet at least the Step 1 classification with current
prescription/use of medications to control symptoms); f) diabetes requiring use of
medicine (insulin or oral) or not controlled with diet.

- Participation in research involving an investigational product (drug/biologic/device)
within 45 days prior to first study vaccination.

- History of a confirmed diagnosis of SARS or COVID-19 disease (confirmed by a specific
test for each disease) or known exposure to a SARS-CoV-2 positive confirmed close
contact (eg, family member, housemate, daycare provider, aged parent requiring care),
at the discretion of the investigator.

- Currently working in an occupation with a high risk of exposure to SARS-CoV-2 (eg,
healthcare worker, emergency response personnel).

- Currently taking any product (investigational or off-label) for prevention of COVID-19
disease.

- Positive rapid test for SARS-CoV-2 (either ELISA IgG or PCR) at screening or prior to
first vaccination. Testing may be repeated during the screening period if exposure to
SARS-CoV-2 is suspected, at the discretion of the investigator.

- Received influenza vaccination within 14 days prior to first study vaccination, or any
other vaccine within 4 weeks prior to first study vaccination.

- Any autoimmune or immunodeficiency disease/condition (iatrogenic or congenital).

- Chronic administration (defined as more than 14 continuous days) of immunosuppressant,
systemic glucocorticosteroids, or other immune-modifying drugs within 90 days prior to
first study vaccination; or anticipation of the need for immunosuppressive treatment
within 6 months after last vaccination.

- Received immunoglobulin, blood-derived products, or other immunosuppressant drugs
within 90 days prior to first study vaccination.

- Any acute illness concurrent or within 14 days prior to first study vaccination
(medical history and/or physical examination) or documented temperature of >38°C
during this period. This includes respiratory or constitutional symptoms consistent
with SARS-CoV-2 (COVID-19) exposure (ie, cough, sore throat, difficulty breathing).

- Known disturbance of coagulation (iatrogenic or congenital).

- Evidence of Hepatitis B or C or HIV by laboratory testing.

- A positive test result for drugs of abuse (except a positive test result associated
with prescription medication that has been reviewed and approved by the investigator)
or alcohol at screening.

- Any neurological disease or history of significant neurological disorder (eg,
meningitis, seizures, multiple sclerosis, vasculitis, migraines, Guillain-Barré
syndrome [genetic/congenital or acquired]).

- Active cancer (malignancy) within 5 years prior to first study vaccination (with the
exception of adequately treated non-melanomatous skin carcinoma, at the discretion of
the investigator)

- Vital sign (blood pressure, pulse, temperature) abnormalities of toxicity grade >1.

- Clinical laboratory abnormalities of toxicity grade >1 for selected serum chemistry
and hematology parameters

- Any known allergies to products contained in the investigational product or latex
allergy.

- Women who are pregnant, breastfeeding or who plan to become pregnant during the study.

- History of alcohol abuse or drug addiction within 1 year prior to the first study
vaccination.

- Any 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 deemed
likely to impair the quality of safety reporting).

- Study team member or first-degree relative of any study team member (inclusive of
sponsor, PPD, and site personnel involved in the study).

Inclusion Criteria (Part 2):

- Healthy adult males or females between 18 and 84 years of age, inclusive, at screening
who are of legal adult age in their local jurisdiction. Healthy status will be
determined by the investigator based on medical history, clinical laboratory results,
vital sign measurements, and physical examination at screening.

- The participant has a body mass index 17 to 35 kg/m2, inclusive, at screening.

- Willing and able to give informed consent prior to study enrollment and comply with
study procedures.

- Female participants of childbearing potential (defined as any female 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 or documented plasma FSH level =40 mIU/mL]) must agree to
be heterosexually inactive from at least 21 days prior to enrollment and through 6
months after the last vaccination OR agree to consistently use any of the following
methods of contraception from at least 21 days prior to enrollment and through 6
months after the last vaccination.

Exclusion Criteria (Part 2):

- Participants who are having any current workup of undiagnosed illness within the last
8 weeks, which is either participant-reported or has been clinician-assessed, that
could lead to a new condition diagnosis.

- Participation in research involving an investigational product (drug/biologic/device)
within 45 days prior to first study vaccination.

- History of a confirmed diagnosis of SARS or history of a confirmed diagnosis of
COVID-19 disease resulting in medical intervention.

- Received influenza vaccination within 14 days prior to first study vaccination, or any
other vaccine within 4 weeks prior to first study vaccination.

- Have clinically significant chronic cardiovascular, endocrine, gastrointestinal/
hepatic, renal, neurological, respiratory, or other medical disorders not excluded by
other exclusion criteria, that are assessed by the Investigator as being clinically
unstable within the prior 4 weeks evidenced by: a) hospitalization for the condition,
including day surgical interventions, b) new significant organ function deterioration,
c) needing addition of new treatments or major dose adjustments of current treatments.

- Diabetes mellitus requiring insulin therapy (either type 1 or type 2 diabetes
mellitus).

- Chronic obstructive pulmonary disease with a history of an acute exacerbation of any
severity in the prior year.

- Any history of congestive heart failure.

- Any history of chronic kidney disease (the presence of impaired or reduced kidney
function lasting at least 3 months). Clinical validation of potential cases of chronic
kidney disease should be conducted.

- Evidence of unstable coronary artery disease as manifested by cardiac intervention,
addition of new cardiac medications for control of symptoms, or unstable angina in the
past 3 months.

- History of chronic neurological disorders that have required prior specialist
physician review for diagnosis and management (such as multiple sclerosis, dementia,
transient ischemic attacks, Parkinson's disease, degenerative neurological conditions,
neuropathy, and epilepsy) or a history of stroke or previous neurological disorder
within 12 months with residual symptoms. Participants with a history of migraine or
chronic headaches or nerve root compression that have been stable on treatment for the
last 4 weeks are not excluded.

- Any autoimmune or immunodeficiency disease/condition (iatrogenic or congenital).

- Chronic administration (defined as more than 14 continuous days) of
immunosuppressants, systemic glucocorticosteroids reaching an immunosuppressive dose,
or other immune-modifying drugs within 90 days prior to first study vaccination.

- Received immunoglobulin, blood-derived products, or other immunosuppressant drugs
within 90 days prior to first study vaccination.

- Known disturbance of coagulation (iatrogenic or congenital).

- Active cancer (malignancy) within 5 years prior to first study vaccination (with the
exception of adequately treated non-melanomatous skin carcinoma, at the discretion of
the investigator).

- Any known allergies to products contained in the investigational product or latex
allergy.

- Women who are breastfeeding or who plan to become pregnant during the study.

- History of alcohol abuse or drug addiction within one year prior to the first study
vaccination.

- Any condition that, in the opinion of the investigator, would pose a health risk to
the subject if enrolled or could interfere with evaluation of the study vaccine or
interpretation of study results (including neurologic or psychiatric conditions deemed
likely to impair the quality of safety reporting).

- Study team member or first-degree relative of any study team member (inclusive of
sponsor, PPD, and site personnel involved in the study).

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC
Recruitment hospital [1] 0 0
Paratus Clinical Research - Canberra - Phase 2 - Bruce
Recruitment hospital [2] 0 0
Paratus Clinical Research - Western Sydney - Phase 2 - Blacktown
Recruitment hospital [3] 0 0
Paratus Clinical Research - Central Coast - Phase 2 - Kanwal
Recruitment hospital [4] 0 0
Australian Clinical Research Network - Phase 2 - Maroubra
Recruitment hospital [5] 0 0
Scientia Clinical Research Limited - Phase 2 - Randwick
Recruitment hospital [6] 0 0
Q Pharm Pty Limited - Phase 1 - Herston
Recruitment hospital [7] 0 0
University of the Sunshine Coast, Health Hub Morayfield - Phase 2 - Morayfield
Recruitment hospital [8] 0 0
University of the Sunshine Coast - Phase 2 - Sippy Downs
Recruitment hospital [9] 0 0
Barwon Health - Phase 2 - Geelong
Recruitment hospital [10] 0 0
Center for Clinical Studies - Phase 1 and Phase 2 - Melbourne
Recruitment postcode(s) [1] 0 0
2617 - Bruce
Recruitment postcode(s) [2] 0 0
2148 - Blacktown
Recruitment postcode(s) [3] 0 0
2259 - Kanwal
Recruitment postcode(s) [4] 0 0
2035 - Maroubra
Recruitment postcode(s) [5] 0 0
2031 - Randwick
Recruitment postcode(s) [6] 0 0
4006 - Herston
Recruitment postcode(s) [7] 0 0
4506 - Morayfield
Recruitment postcode(s) [8] 0 0
4556 - Sippy Downs
Recruitment postcode(s) [9] 0 0
3220 - Geelong
Recruitment postcode(s) [10] 0 0
3181 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
Idaho
Country [3] 0 0
United States of America
State/province [3] 0 0
Kansas
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novavax
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Coalition for Epidemic Preparedness Innovations (CEPI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
2019nCoV-101 is a 2-part, randomized, observer-blinded, placebo-controlled, Phase 1/2 trial.
Part 1 (Phase 1) of the study is designed to evaluate the safety and immunogenicity of
SARS-CoV-2 rS nanoparticle vaccine with or without Matrix-M adjuvant in 131 healthy
participants = 18 to 59 (inclusive) years of age at 2 sites in Australia. An interim analysis
of Part 1 safety and immunogenicity will be performed prior to optional expansion to Part 2.
Part 2 (Phase 2) of the study is designed to evaluate the immunogenicity, safety, and
preliminary efficacy of a single construct of SARS-CoV-2 rS nanoparticle vaccine with
Matrix-M adjuvant in up to 1,500 healthy participants = 18 to 84 (inclusive) years of age at
up to 40 sites across Australia and/or the United States.
Trial website
https://clinicaltrials.gov/show/NCT04368988
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications