A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial to Evaluate Safety, Tolerability, and Immune Responses of an Investigational Monovalent Chimpanzee Adenoviral Vectored Sudan Ebolavirus Vaccine in Healthy Adults
This is a multi-center, double-blinded, placebo-controlled, Phase 2 study to evaluate safety, tolerability, and immunogenicity of a single dose of cAd3-Sudan Vaccine in healthy adults up to 70 years of age. The study will enroll 200 eligible participants randomized 4:1 to receive the cAd3-Sudan Vaccine at 1.0 × 10\^11 PU dose or placebo (0.9% sodium chloride (NaCl) solution) at Day 1, intramuscularly in deltoid muscle. Participants will be screened for eligibility up to 28 days before enrollment. Safety data will be periodically reviewed by an independent DSMB. Safety and immunogenicity will be assessed at Days 1, 8, 15, 29, 85, 169, and will conclude at the end of study visit on Day 366. PBMCs will be collected from a subset of 40 subjects on days 1, 15, 29, 169 and 366 to access cellular immunity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
200
The recombinant chimpanzee adenovirus Type 3-vectored Sudan Ebolavirus vaccine, (cAd3-Sudan) is composed of a cAd3 vector that expresses wild type glycoprotein (WT GP) from the Sudan Gulu ebolavirus strain.
0.9% NaCl solution for injection.
Synexus Clinical Research US, Inc.
Phoenix, Arizona, United States
Optimal Research; LLC
Melbourne, Florida, United States
Synexus Clinical Research US, Inc.
Chicago, Illinois, United States
Synexus Clinical Research US, Inc.
San Antonio, Texas, United States
To determine the percentage of vaccinated participants who develop SAEs, AEs, and AESI from cAd3-Sudan Vaccine and placebo
Count and percentage of vaccinated participants who develop: - serious adverse events (SAEs), - solicited adverse events (AEs), - unsolicited AEs, - adverse event of special interest (AESI), - medically attended adverse events (MAAE), - AE at each intensity level. Estimand 1a (Primary): Count and percentage of vaccinated participants who would develop SAEs, solicited AEs, unsolicited AEs, AESI, MAAE, and AE at each intensity level will be evaluated with each treatment group. A treatment policy strategy is used for assessing safety irrespective of a current (or prior) infection at time of the vaccination. Infections and death (if the participant meet the AE and time window criteria) are included in the endpoint (composite strategy).
Time frame: 1 Year
To determine the geometric mean concentration (GMC) of the antibody response (IgG) to cAd3-Sudan Vaccine at Day 29 post-vaccination.
Secondary Endpoint: To evaluate the humoral immunogenicity of anti-SUDV-GP binding IgG antibodies at Day 29 post-vaccination. Estimand 2a: Geometric mean concentration (GMC) of the vaccine group will be compared to placebo at Day 29 post-vaccination. The hypothetical strategy is used to estimate antibody levels without subsequent Sudan Ebolavirus (SUDV) infection or influence from immune-modifying drugs or non-study vaccines. The principal stratum strategy excludes those with active or prior SUDV infection at the time of the vaccination.
Time frame: 29 Days
To determine geometric mean increase (GMI) of anti-SUDV-GP binding IgG antibodies at Day 29 post-vaccination
Secondary Endpoint: To evaluate the humoral immunogenicity of anti-SUDV-GP binding IgG antibodies at Day 29 post-vaccination. Estimand 2b: Geometric mean increase (GMI) of anti-SUDV-GP binding IgG antibodies against SUDV-GP on Day 29. The hypothetical strategy is used to estimate antibody levels without subsequent Sudan Ebolavirus (SUDV) infection or influence from immune-modifying drugs or non-study vaccines. The principal stratum strategy excludes those with active or prior SUDV infection at the time of the vaccination.
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Time frame: 29 Days
To determine the geometric mean of the ND50 (GMND50) of anti-SUDV-GP neutralizing antibodies on Day 29 post-vaccination.
Secondary Endpoint: To evaluate the humoral immunogenicity of anti-SUDV-GP binding IgG antibodies at Day 29 post-vaccination. Estimand 2c: The geometric mean of the ND50 (GMND50) of anti-SUDV-GP neutralizing antibodies on Day 29. The hypothetical strategy is used to estimate antibody levels without subsequent Sudan Ebolavirus (SUDV) infection or influence from immune-modifying drugs or non-study vaccines. The principal stratum strategy excludes those with active or prior SUDV infection at the time of the vaccination.
Time frame: 29 Days
To determine the geometric mean increase of the ND50 (GMIND50) of anti-SUDV-GP neutralizing antibodies at Day 29 post-vaccination.
Secondary Endpoint: To evaluate the humoral immunogenicity of anti-SUDV-GP binding IgG antibodies at Day 29 post-vaccination. Estimand 2d: The geometric mean increase of the ND50 (GMIND50) of anti-SUDV-GP neutralizing antibodies on Day 29. The hypothetical strategy is used to estimate antibody levels without subsequent Sudan Ebolavirus (SUDV) infection or influence from immune-modifying drugs or non-study vaccines. The principal stratum strategy excludes those with active or prior SUDV infection at the time of the vaccination.
Time frame: 29 Days
To determine the percentage of participants (and 95%CI) with seroconversion at Day 29 post-vaccination.
Secondary Endpoint: Humoral immunogenicity of anti-SUDV-GP binding IgG antibodies at Day 29 post-vaccination. Estimand 2e: Percentage of participants (and 95%CI) with seroconversion at Day 29. The hypothetical strategy is used to estimate antibody levels without subsequent Sudan Ebolavirus (SUDV) infection or influence from immune-modifying drugs or non-study vaccines. The principal stratum strategy excludes those with active or prior SUDV infection at the time of the vaccination.
Time frame: 29 Days
To determine the geometric mean concentration (GMC) of anti-SUDV-GP binding IgG antibodies on Day 1, Day 8, Day 15, Day 85, Day 169, and Day 366.
Secondary Endpoint: To evaluate the humoral immunogenicity of anti-SUDV-GP binding IgG antibodies across additional timepoints. Estimand 3a: GMCs of anti-SUDV-GP binding IgG antibodies on Day 1, Day 8, Day 15, Day 85, Day 169, and Day 366. The hypothetical strategy is used to estimate antibody levels without subsequent Sudan Ebolavirus (SUDV) infection or influence from immune-modifying drugs or non-study vaccines.
Time frame: 1 Year
To determine the geometric mean increase (GMI) of anti-SUDV-GP binding IgG antibodies against SUDV-GP at optional selected timepoints (Day 8, Day 15, Day 85, Day 169, and Day 366).
Secondary Endpoint: To evaluate the humoral immunogenicity of anti-SUDV-GP binding IgG antibodies across additional timepoints. Estimand 3b: GMI of anti-SUDV-GP binding IgG antibodies against SUDV-GP at optional selected timepoints (Day 8, Day 15, Day 85, Day 169, and Day 366). The hypothetical strategy is used to estimate antibody levels without subsequent Sudan Ebolavirus (SUDV) infection or influence from immune-modifying drugs or non-study vaccines.
Time frame: 1 Year
To determine geometric mean increase of the ND50 (GMIND50) of anti-SUDV-GP neutralizing antibodies on Day 1, Day 8, Day 15, Day 85, Day 169, and Day 366.
Secondary Endpoint: To evaluate the humoral immunogenicity of anti-SUDV-GP binding IgG antibodies across additional timepoints. Estimand 3c: GMIND50 of anti-SUDV-GP neutralizing antibodies on Day 1, Day 8, Day 15, Day 85, Day 169, and Day 366. The hypothetical strategy is used to estimate antibody levels without subsequent Sudan Ebolavirus (SUDV) infection or influence from immune-modifying drugs or non-study vaccines.
Time frame: 1 Year
To determine geometric mean increase of ND50 (GMIND50) of anti-SUDV-GP neutralizing antibodies at optionally selected timepoints (Day 8, Day 15, Day 85, Day 169, and Day 366)
Secondary Endpoint: To evaluate the humoral immunogenicity of anti-SUDV-GP binding IgG antibodies across additional timepoints. Estimand 3d: GMIND50 of anti-SUDV-GP neutralizing antibodies at optionally selected timepoints (Day 8, Day 15, Day 85, Day 169, and Day 366). The hypothetical strategy is used to estimate antibody levels without subsequent Sudan Ebolavirus (SUDV) infection or influence from immune-modifying drugs or non-study vaccines.
Time frame: 1 Year
To determine the percentage of participants (and 95%CI) with seroconversion at Day 8, Day 15, Day 85, Day 169, and Day 366.
Secondary Endpoint: To evaluate the humoral immunogenicity of anti-SUDV-GP binding IgG antibodies across additional timepoints. Estimand 3e: Percentage of Participants (and 95%CI) with seroconversion at Day 8, Day 15, Day 85, Day 169, and Day 366. The hypothetical strategy is used to estimate antibody levels without subsequent Sudan Ebolavirus (SUDV) infection or influence from immune-modifying drugs or non-study vaccines.
Time frame: 1 Year