COVID-19 Supplemental Vaccine Boost to Enhance T Cell Protection in Those Who Have Already Received EUA S-Based Vaccines
Primary Purpose
Covid19
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
hAd5-S-Fusion+N-ETSD vaccine
Sponsored by
About this trial
This is an interventional treatment trial for Covid19
Eligibility Criteria
Inclusion Criteria:
Healthy adults, age ≥ 18 years, inclusive, at time of enrollment, that have previously received an FDA-authorized COVID-19 vaccine (both prime and boost) ≥14 days and
≤ 6 months before enrollment.
- Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
- Agrees to the collection of biospecimens (eg, NP swabs and/or saliva sample) and venous blood per protocol.
- Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
- Ability to swallow a capsule.
- Temperature < 38°C.
- Agreement to practice effective contraception for female subjects of childbearing potential and non-sterile males. Female subjects of childbearing potential must agree to use effective contraception while on study until at least 1 month after the last dose of vaccine. Non-sterile male subjects must agree to use a condom while on study until at least 1 month after the last dose of vaccine. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, IUDs, oral contraceptives, and abstinence.
Exclusion Criteria:
- Persistent grade ≥ 2 AEs related to previous COVID-19 vaccination at the time of enrollment.
- Allergy to any component of the investigational vaccine, or a more severe allergic reaction and history of allergies in the past.
- Pregnant and nursing women. A negative serum or urine pregnancy test during screening and on the day of and prior to each dose must be documented before the vaccine is administered to a female subject of childbearing potential.
- Chronic lung disease including chronic obstructive pulmonary disease (COPD) or moderate to severe asthma.
- Pulmonary fibrosis.
- Bone marrow or organ transplantation.
- Extreme obesity (defined as BMI of 35 kg/m2 or higher).
- Diabetes.
- Chronic kidney disease.
- Liver disease.
- Sickle cell disease.
- Thalassemia.
- Any disease associated with acute fever, or any infection.
- Self-reported history of SARS.
- History of hepatitis B or hepatitis C.
- HIV or other acquired or hereditary immunodeficiency.
- Serious cardiovascular diseases, such as heart failure, coronary artery disease, cardiomyopathies, arrhythmia, conduction block, myocardial infarction, pulmonary hypertension, severe hypertension without controllable drugs, etc.
- Cerebrovascular disease.
- Cystic fibrosis.
- Neurologic conditions, such as dementia.
- Hereditary or acquired angioneurotic edema.
- No spleen or functional asplenia.
- Platelet disorder or other bleeding disorder that may cause injection contraindication.
- Chronic use (more than 14 continuous days) of any medications that may be associated with impaired immune responsiveness within 3 months before administration of study vaccine. (Including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone equivalent, allergy injections, immunoglobulin, interferon, immunomodulators. The use of low dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted.)
- Prior administration of blood products in last 4 months.
- Currently receiving treatment for cancer or history of cancer in the last five years (except basal cell carcinoma of the skin and cervical carcinoma in situ).
- According to the judgement of investigator, various medical, psychological, social or other conditions that could affect the subjects ability to sign informed consent.
- Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1: hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous
Cohort 2: hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous and 1 × 10e10 IU/dose Sublingual
Arm Description
Cohort 1 (n=20): hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous on Day 1
Cohort 2 (n=20): hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous and 1 × 10e10 IU/dose Sublingual on Day 1
Outcomes
Primary Outcome Measures
Phase 1 Safety: Incidence of MAAEs and SAEs
Incidence of MAAEs and SAEs through 1 week post final vaccine administration
Phase 1 Safety: Incidence and severity of solicited local reactogenicity AEs
Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration
Phase 1 Safety: Incidence and severity of solicited systemic reactogenicity AEs
Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration
Phase 1 Safety: Incidence and severity of unsolicited AEs
Incidence and severity of unsolicited AEs through 1 week post final vaccine administration
Phase 1 Safety: Incidence of MAAEs and SAEs
Incidence of MAAEs and SAEs through 30 days and 6 months post final vaccine administration
Phase 1 Safety: Incidence and severity of unsolicited AEs
Incidence and severity of unsolicited AEs through 30 days post final vaccine administration
Phase 1 Safety: Incidence of changes of laboratory safety examinations
Incidence of abnormal changes of laboratory safety examinations
Phase 1 Safety: Vital Sign - Temperature
Changes in vital signs from Grades 1-4:
measured in (°C) or (°F)
Phase 1 Safety: Vital Sign - Heart Rate
Changes in vital signs from Grades 1-4:
measured by how many heart beats per minute
Phase 1 Safety: Vital Sign - Blood Pressure
Changes in vital signs from Grades 1-4:
systolic/diastolic - measured in mm Hg
Phase 1 Safety: Vital Sign - Respiratory Rate
Changes in vital signs from Grades 1-4:
measured in how many breaths per minute
Phase 2 Efficacy: Percent of subjects that show an increase in N-reactive T cells
Percent of subjects that show an increase in N-reactive T cells as assayed by N-Tiferon assay (≥ 25 pg/mL increase in cytokine concentration from baseline)
Secondary Outcome Measures
Phase 1 Humoral Immunogenicity: GMT of S-specific and N-specific antibodies
GMT of S-specific and N-specific antibodies against 2019 novel coronavirus
Phase 1 Humoral Immunogenicity: GMT of neutralizing antibody
GMT of neutralizing antibody
Phase 1 Mucosal Immunogenicity: GMT of IgA antibody levels
GMT of IgA antibody levels
Phase 1 Cellular Immunogenicity: T cell activity
T cell activity against SARS-CoV-2 S protein and N protein. ImmunityBio has developed a rapid assay (N-Tiferon) to detect SARS-CoV-2-specific T cell responses directly in whole blood from participants in QUILT-4.001 vaccinated with hAd5 S-Fusion+N-ETSD targeting the S and N antigens of SARS-CoV-2. This assay detected interferon-γ (IFN-γ)-secreting S- and N-specific T cells directly in whole blood post-vaccination.
Phase 2 Efficacy: Incidence and severity of COVID-19 ≥14 days after vaccination
Incidence and severity of COVID-19 ≥14 days after vaccination in subjects with no evidence of past SARS-CoV-2 infection. It applies to ≥3 for injection site reaction, fever, and other AEs. It also includes signs and symptoms of hypersensitivity which may include red rash (excluding site of injection), swollen throat or swollen areas of the body, wheezing, fainting, chest tightness, difficulty breathing, hoarse voice, difficulty swallowing, vomiting, diarrhea, and stomach cramping.
Phase 2 Efficacy: Mean SARS-CoV-2 viral load
Mean SARS-CoV-2 viral load for subjects with confirmed COVID-19 ≥14 days after vaccination
Phase 2 Efficacy: Humoral Immunogenicity - GMT of S-specific and N-specific antibodies
GMT of S-specific and N-specific antibodies against 2019 novel coronavirus
Phase 2 Efficacy: Humoral Immunogenicity - GMT of neutralizing antibody
GMT of neutralizing antibody
Phase 2 Efficacy: Mucosal Immunogenicity - GMT of IgA antibody levels
GMT of IgA antibody levels
Phase 2 Efficacy: Cellular Immunogenicity - T cell activity
T cell activity against SARS-CoV-2 S protein and N protein measured
Phase 2 Safety: Incidence of MAAEs and SAEs
Incidence of MAAEs and SAEs through 1 week post final vaccine administration
Phase 2 Safety: Incidence and severity of solicited local reactogenicity AEs
Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration
Phase 2 Safety: Incidence and severity of solicited systemic reactogenicity AEs
Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration
Phase 2 Safety: Incidence and severity of unsolicited AEs
Incidence and severity of unsolicited AEs through 1 week post final vaccine administration
Phase 2 Safety: Incidence of MAAEs and SAEs
Incidence of MAAEs and SAEs through 30 days and 6 months post final vaccine administration
Phase 2 Safety: Incidence and severity of unsolicited AEs
Incidence and severity of unsolicited AEs through 30 days post final vaccine administration
Phase 2 Safety: Incidence of changes of laboratory safety examinations
Incidence of abnormal changes of laboratory safety examinations
Phase 2 Safety: Vital Sign - Temperature
Changes in vital signs from Grades 1-4:
measured in (°C) or (°F)
Phase 2 Safety: Vital Sign - Heart rate
Changes in vital signs from Grades 1-4:
measured by how many heart beats per minute
Phase 2 Safety: Vital Sign - Blood Pressure
Changes in vital signs from Grades 1-4:
systolic/diastolic - measured in mm Hg
Phase 2 Safety: Vital Sign - Respiratory rate
Changes in vital signs from Grades 1-4:
measured in how many breaths per minute
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04843722
Brief Title
COVID-19 Supplemental Vaccine Boost to Enhance T Cell Protection in Those Who Have Already Received EUA S-Based Vaccines
Official Title
Phase 1/2 Study of the Safety, Reactogenicity, and Immunogenicity of a Supplemental Spike & Nucleocapsid-targeted COVID-19 Vaccine to Enhance T Cell Based Immunogenicity in Participants Who Have Already Received Prime + Boost Vaccines Authorized For Emergency Use
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Withdrawn
Why Stopped
The sponsor has changed the development plans which is not for safety reasons.
Study Start Date
December 2021 (Anticipated)
Primary Completion Date
March 2022 (Anticipated)
Study Completion Date
August 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ImmunityBio, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a phase 1/2 study in adult healthy subjects that have previously been vaccinated with an FDA-authorized vaccine against COVID-19. This clinical trial is designed to assess the safety, efficacy, reactogenicity, and immunogenicity of hAd5-S-Fusion+N-ETSD formulated for subcutaneous, sublingual, and oral (capsule) administration.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Open label 2 Cohort Phase 1 Study leading to Randomized Phase 2 Study
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous
Arm Type
Experimental
Arm Description
Cohort 1 (n=20): hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous on Day 1
Arm Title
Cohort 2: hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous and 1 × 10e10 IU/dose Sublingual
Arm Type
Experimental
Arm Description
Cohort 2 (n=20): hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous and 1 × 10e10 IU/dose Sublingual on Day 1
Intervention Type
Biological
Intervention Name(s)
hAd5-S-Fusion+N-ETSD vaccine
Intervention Description
Vaccine containing both full length wild type SARS-CoV-2 spike gene optimized for better spike protein expression, and full length wild type SARS-CoV-2 nucleocapsid gene modified to also contain an enhanced T cell stimulation domain (ETSD) to enhance cell-mediated immunity.
Primary Outcome Measure Information:
Title
Phase 1 Safety: Incidence of MAAEs and SAEs
Description
Incidence of MAAEs and SAEs through 1 week post final vaccine administration
Time Frame
through 1 week post final vaccine administration
Title
Phase 1 Safety: Incidence and severity of solicited local reactogenicity AEs
Description
Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration
Time Frame
through 1 week post final vaccine administration
Title
Phase 1 Safety: Incidence and severity of solicited systemic reactogenicity AEs
Description
Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration
Time Frame
through 1 week post final vaccine administration
Title
Phase 1 Safety: Incidence and severity of unsolicited AEs
Description
Incidence and severity of unsolicited AEs through 1 week post final vaccine administration
Time Frame
through 1 week post final vaccine administration
Title
Phase 1 Safety: Incidence of MAAEs and SAEs
Description
Incidence of MAAEs and SAEs through 30 days and 6 months post final vaccine administration
Time Frame
through 30 days and 6 months post final vaccine administration
Title
Phase 1 Safety: Incidence and severity of unsolicited AEs
Description
Incidence and severity of unsolicited AEs through 30 days post final vaccine administration
Time Frame
through 30 days post final vaccine administration
Title
Phase 1 Safety: Incidence of changes of laboratory safety examinations
Description
Incidence of abnormal changes of laboratory safety examinations
Time Frame
Day 365
Title
Phase 1 Safety: Vital Sign - Temperature
Description
Changes in vital signs from Grades 1-4:
measured in (°C) or (°F)
Time Frame
Day 365
Title
Phase 1 Safety: Vital Sign - Heart Rate
Description
Changes in vital signs from Grades 1-4:
measured by how many heart beats per minute
Time Frame
Day 365
Title
Phase 1 Safety: Vital Sign - Blood Pressure
Description
Changes in vital signs from Grades 1-4:
systolic/diastolic - measured in mm Hg
Time Frame
Day 365
Title
Phase 1 Safety: Vital Sign - Respiratory Rate
Description
Changes in vital signs from Grades 1-4:
measured in how many breaths per minute
Time Frame
Day 365
Title
Phase 2 Efficacy: Percent of subjects that show an increase in N-reactive T cells
Description
Percent of subjects that show an increase in N-reactive T cells as assayed by N-Tiferon assay (≥ 25 pg/mL increase in cytokine concentration from baseline)
Time Frame
from baseline to Day 365
Secondary Outcome Measure Information:
Title
Phase 1 Humoral Immunogenicity: GMT of S-specific and N-specific antibodies
Description
GMT of S-specific and N-specific antibodies against 2019 novel coronavirus
Time Frame
Day 365
Title
Phase 1 Humoral Immunogenicity: GMT of neutralizing antibody
Description
GMT of neutralizing antibody
Time Frame
Day 365
Title
Phase 1 Mucosal Immunogenicity: GMT of IgA antibody levels
Description
GMT of IgA antibody levels
Time Frame
Day 365
Title
Phase 1 Cellular Immunogenicity: T cell activity
Description
T cell activity against SARS-CoV-2 S protein and N protein. ImmunityBio has developed a rapid assay (N-Tiferon) to detect SARS-CoV-2-specific T cell responses directly in whole blood from participants in QUILT-4.001 vaccinated with hAd5 S-Fusion+N-ETSD targeting the S and N antigens of SARS-CoV-2. This assay detected interferon-γ (IFN-γ)-secreting S- and N-specific T cells directly in whole blood post-vaccination.
Time Frame
Day 365
Title
Phase 2 Efficacy: Incidence and severity of COVID-19 ≥14 days after vaccination
Description
Incidence and severity of COVID-19 ≥14 days after vaccination in subjects with no evidence of past SARS-CoV-2 infection. It applies to ≥3 for injection site reaction, fever, and other AEs. It also includes signs and symptoms of hypersensitivity which may include red rash (excluding site of injection), swollen throat or swollen areas of the body, wheezing, fainting, chest tightness, difficulty breathing, hoarse voice, difficulty swallowing, vomiting, diarrhea, and stomach cramping.
Time Frame
≥14 days after vaccination
Title
Phase 2 Efficacy: Mean SARS-CoV-2 viral load
Description
Mean SARS-CoV-2 viral load for subjects with confirmed COVID-19 ≥14 days after vaccination
Time Frame
Day 365
Title
Phase 2 Efficacy: Humoral Immunogenicity - GMT of S-specific and N-specific antibodies
Description
GMT of S-specific and N-specific antibodies against 2019 novel coronavirus
Time Frame
Day 365
Title
Phase 2 Efficacy: Humoral Immunogenicity - GMT of neutralizing antibody
Description
GMT of neutralizing antibody
Time Frame
Day 365
Title
Phase 2 Efficacy: Mucosal Immunogenicity - GMT of IgA antibody levels
Description
GMT of IgA antibody levels
Time Frame
Day 365
Title
Phase 2 Efficacy: Cellular Immunogenicity - T cell activity
Description
T cell activity against SARS-CoV-2 S protein and N protein measured
Time Frame
Day 365
Title
Phase 2 Safety: Incidence of MAAEs and SAEs
Description
Incidence of MAAEs and SAEs through 1 week post final vaccine administration
Time Frame
through 1 week post final vaccine administration
Title
Phase 2 Safety: Incidence and severity of solicited local reactogenicity AEs
Description
Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration
Time Frame
through 1 week post final vaccine administration
Title
Phase 2 Safety: Incidence and severity of solicited systemic reactogenicity AEs
Description
Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration
Time Frame
through 1 week post final vaccine administration
Title
Phase 2 Safety: Incidence and severity of unsolicited AEs
Description
Incidence and severity of unsolicited AEs through 1 week post final vaccine administration
Time Frame
through 1 week post final vaccine administration
Title
Phase 2 Safety: Incidence of MAAEs and SAEs
Description
Incidence of MAAEs and SAEs through 30 days and 6 months post final vaccine administration
Time Frame
through 30 days and 6 months post final vaccine administration
Title
Phase 2 Safety: Incidence and severity of unsolicited AEs
Description
Incidence and severity of unsolicited AEs through 30 days post final vaccine administration
Time Frame
through 30 days post final vaccine administration
Title
Phase 2 Safety: Incidence of changes of laboratory safety examinations
Description
Incidence of abnormal changes of laboratory safety examinations
Time Frame
Day 365
Title
Phase 2 Safety: Vital Sign - Temperature
Description
Changes in vital signs from Grades 1-4:
measured in (°C) or (°F)
Time Frame
Day 365
Title
Phase 2 Safety: Vital Sign - Heart rate
Description
Changes in vital signs from Grades 1-4:
measured by how many heart beats per minute
Time Frame
Day 365
Title
Phase 2 Safety: Vital Sign - Blood Pressure
Description
Changes in vital signs from Grades 1-4:
systolic/diastolic - measured in mm Hg
Time Frame
Day 365
Title
Phase 2 Safety: Vital Sign - Respiratory rate
Description
Changes in vital signs from Grades 1-4:
measured in how many breaths per minute
Time Frame
Day 365
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy adults, age ≥ 18 years, inclusive, at time of enrollment, that have previously received an FDA-authorized COVID-19 vaccine (both prime and boost) ≥14 days and
≤ 6 months before enrollment.
Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
Agrees to the collection of biospecimens (eg, NP swabs and/or saliva sample) and venous blood per protocol.
Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
Ability to swallow a capsule.
Temperature < 38°C.
Agreement to practice effective contraception for female subjects of childbearing potential and non-sterile males. Female subjects of childbearing potential must agree to use effective contraception while on study until at least 1 month after the last dose of vaccine. Non-sterile male subjects must agree to use a condom while on study until at least 1 month after the last dose of vaccine. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, IUDs, oral contraceptives, and abstinence.
Exclusion Criteria:
Persistent grade ≥ 2 AEs related to previous COVID-19 vaccination at the time of enrollment.
Allergy to any component of the investigational vaccine, or a more severe allergic reaction and history of allergies in the past.
Pregnant and nursing women. A negative serum or urine pregnancy test during screening and on the day of and prior to each dose must be documented before the vaccine is administered to a female subject of childbearing potential.
Chronic lung disease including chronic obstructive pulmonary disease (COPD) or moderate to severe asthma.
Pulmonary fibrosis.
Bone marrow or organ transplantation.
Extreme obesity (defined as BMI of 35 kg/m2 or higher).
Diabetes.
Chronic kidney disease.
Liver disease.
Sickle cell disease.
Thalassemia.
Any disease associated with acute fever, or any infection.
Self-reported history of SARS.
History of hepatitis B or hepatitis C.
HIV or other acquired or hereditary immunodeficiency.
Serious cardiovascular diseases, such as heart failure, coronary artery disease, cardiomyopathies, arrhythmia, conduction block, myocardial infarction, pulmonary hypertension, severe hypertension without controllable drugs, etc.
Cerebrovascular disease.
Cystic fibrosis.
Neurologic conditions, such as dementia.
Hereditary or acquired angioneurotic edema.
No spleen or functional asplenia.
Platelet disorder or other bleeding disorder that may cause injection contraindication.
Chronic use (more than 14 continuous days) of any medications that may be associated with impaired immune responsiveness within 3 months before administration of study vaccine. (Including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone equivalent, allergy injections, immunoglobulin, interferon, immunomodulators. The use of low dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted.)
Prior administration of blood products in last 4 months.
Currently receiving treatment for cancer or history of cancer in the last five years (except basal cell carcinoma of the skin and cervical carcinoma in situ).
According to the judgement of investigator, various medical, psychological, social or other conditions that could affect the subjects ability to sign informed consent.
Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
COVID-19 Supplemental Vaccine Boost to Enhance T Cell Protection in Those Who Have Already Received EUA S-Based Vaccines
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