- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04608305
Evaluate the Safety, Immunogenicity and Potential Efficacy of an rVSV-SARS-CoV-2-S Vaccine
A Phase I/II Randomized, Multi-Center, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Immunogenicity and Potential Efficacy of an rVSV-SARS-CoV-2-S Vaccine (IIBR-100) in Adults
The SARS-CoV-2 virus is responsible for the COVID-19 pandemic. The pandemic emerged from Wuhan Province in China in December 2019 and was declared by the WHO Director-General a Public Health Emergency of International Concern on 30 January 2020.
In this study, a vaccine developed by IIBR for SARS-CoV-2 virus will be assessed for its safety and potential efficacy in volunteers. The study is comprised of two phases, a dose-escalation phase (phase I) during which subjects (18-55 years old) will be randomly allocated to receive a single administration of IIBR-100 at low, mid or high dose or saline or two administrations of IIBR-100 at low dose, or saline, 28 days apart.
Based on results obtained during phase I, and cumulative phase I data review, the expansion phase (phase II) has begun, during which larger cohorts as well as elderly age subjects were initially planned to be randomly allocated to receive a single administration of IIBR-100 at low, mid or high dose or saline, or two administrations of IIBR-100 at low, mid or high dose (prime-boost) or saline, 28 days apart. Additional top-dose (prime-boost) may be implemented when immunogenicity of any prime-boost arm is considered insufficient. However, based on immunogenicity preliminary data and DSMB recommendations, only the two administrations of mid, high and top dose (prime-boost) or saline will continue in the study.
The subjects will be followed for a period of up to 12 months post last vaccine administration to assess the safety and efficacy of the vaccine.
Study Overview
Status
Conditions
Intervention / Treatment
- Biological: IIBR-100, low dose (prime)
- Other: Saline Placebo (single)
- Biological: IIBR-100 medium dose (prime)
- Biological: IIBR-100 high-dose (prime)
- Biological: IIBR-100 low-dose (prime-boost)
- Other: Saline Placebo (double)
- Biological: IIBR-100 medium-dose (prime-boost)
- Biological: IIBR-100 high-dose (prime-boost)
- Biological: IIBR-100 top-dose (prime-boost)
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Hadar Marcus, Dr.
- Phone Number: 972-50-6234230
- Email: IIBR100_1@iibr.gov.il
Study Contact Backup
- Name: Noa Madar Balakirski, Dr.
- Phone Number: 972-50-6234202
- Email: IIBR100_2@iibr.gov.il
Study Locations
-
-
-
Ashdod, Israel
- Assuta - University Hospital
-
Ashkelon, Israel
- Barzilai MC
-
Haifa, Israel
- Rambam MC
-
Jerusalem, Israel, 91120
- Hadassah Medical Center
-
Kfar Saba, Israel
- Meir MC
-
Petach Tikva, Israel
- Rabin MC
-
Ramat Gan, Israel, 52621
- Sheba Medical Center Hospital- Tel Hashomer
-
Tel Aviv, Israel
- Sourasky MC
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Phase I (abbreviated):
- Healthy males or females, ages 18 to 55 (inclusive) at the time of screening.
- Negative PCR and no presence of ELISA antibody titers to SARS-CoV-2 at screening.
- Females of childbearing potential and males must be willing to use effective methods of contraception such as hormones (OCP, oral contraceptive pill), condom or occlusive cap with spermicidal agents, intrauterine device (IUD) or intrauterine system (IUS) from at least 14 days prior to vaccination through 90 days following last injection.
- Subjects in general good health with no chronic disease nor consumes chronic medication in the opinion of the investigator as determined by medical history, vital signs and a physical examination.
- No clinically significant abnormalities in hematology, blood chemistry, or urinalysis laboratory tests at screening.
- Negative HIV, Hepatitis B and Hepatitis C serology tests.
- Normal oral temperature, normal sinus rhythm, pulse rate no greater than 100 beats per minute and normal systolic blood pressure (below 140/90 mmHg)
- Must be willing to forgo blood donation during the blood drawing phase of the study.
- Must agree not to enroll in another study of an investigational agent prior to completion of the study.
- Subjects must be able to understand the requirements of the study and must be accessible and willing to comply with the study procedures even under lock down conditions.
- Ability to provide informed consent.
Phase II (abbreviated):
- Males or females, ages 18 to 85 (inclusive) at the time of screening.
- Negative PCR and no presence of ELISA antibody titers to SARS-CoV-2 at screening.
- Females of childbearing potential and males must be willing to use effective methods of contraception such as hormones (OCP, oral contraceptive pill), condom or occlusive cap with spermicidal agents, intrauterine device (IUD) or intrauterine system (IUS) from at least 14 days prior to vaccination through 90 days following last injection. Male must agree to avoid sperm donation from time of first injection through 90 days following last injection.
- No clinically significant abnormalities in hematology, blood chemistry, or urinalysis laboratory tests at screening.
- Must be willing to forgo blood donation during the blood drawing phase of the study
- Must agree not to enroll in another study of an investigational agent prior to completion of the study.
- Normal oral temperature, pulse rate no greater than 100 beats per minute (sinus rhythm) and controlled blood pressure (in the case of hypertensives under treatment, below 140/90 mmHg).
- Subjects must be able to understand the requirements of the study and must be accessible and willing to comply with the study procedures even under lock down conditions.
- Ability to provide informed consent.
Exclusion Criteria:
Phase I (abbreviated):
- History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions or known allergy to the components of the vaccine, including allergy to rice.
- Receipt of investigational product up to 30 days prior to screening or ongoing participation in another clinical trial
- Receipt of licensed vaccines within 14 days of planned study immunization and any AE's possibly related to licensed vaccine immunization at Day 0.
- Inability to observe possible local reactions at the injection sites due to a physical condition or permanent body art.
- Known hemoglobinopathy or coagulation abnormality.
- New onset of fever >37.8 ºC AND [cough OR shortness of breath OR anosmia/ageusia] or any other inter current illness within 14 days prior to screening
- High risk of exposure to SARS-CoV-2 prior to enrollment (close contact, self-isolation at present due to household contact, frontline healthcare provider in contact with COVID-19 subjects).
- Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health, per the best clinical judgement of the investigator.
- Women who are pregnant or breastfeeding.
- Positive urine pregnancy test or women have an intention to be pregnant during the study.
- Confirmed or suspected illness caused by coronaviruses, SARS-CoV 1, and Middle East Respiratory Syndrome (MERS)-CoV.
- Received any prior vaccine against a coronavirus
- Receipt of blood/plasma products or immunoglobulin, from within 60 days before study intervention administration or planned receipt throughout the study.
- History of alcohol or drug abuse per clinical judgement within 5 years prior to study vaccination.
- Participants who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol.
- Any other significant finding that in the opinion of the investigator would increase the risk of the individual having an adverse outcome from participating in this study.
- Individuals who are living with severely immunocompromised people (e.g. transplant patients, those under active cancer immunosuppressant therapy), pregnant women, lactating women, children under 12 months old, or any other individual that, in the judgment of the investigator, might be at increased risk.
Phase II (abbreviated):
- History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions or known allergy to the components of the vaccine, including allergy to rice.
- Receipt of investigational product (except of confirmed placebo in IIBR20-001 study) up to 30 days prior to screening or ongoing participation in another clinical trial (except of IIBR20-001 trial).
- Receipt of licensed vaccines within 14 days of planned study immunization and any AE's possibly related to licensed vaccine immunization at Day 0.
- Inability to observe possible local reactions at the injection sites due to a physical condition or permanent body art.
- Known hemoglobinopathy or coagulation abnormality (subjects treated by anticoagulation or anti platelets are not excluded).
- New onset of fever >37.8ºC AND [cough OR shortness of breath OR anosmia/ageusia], or any other inter current illness within 14 days prior to screening
- Factors that increase risk to the subject to severe disease per CDC guidance including the following risk factors (in any case of ambiguous grading, decision will be made per investigator's best clinical judgement): Cancer [ongoing malignancy or recently diagnosed malignancy in the last five years, not including non-melanotic skin cancer], Chronic Kidney Disease (eGFR<60 mL/min/1.73 m^2), liver disease (ALT or AST) > 1.5 × ULN; or alkaline phosphatase and direct bilirubin > ULN (total bilirubin may be up to 2 × ULN as long as direct bilirubin is equal to or below the ULN); or PT INR > 1.25), COPD; Immunocompromised state from solid organ transplant; Obesity (BMI≥30kg/m2); Serious heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies; Sickle cell disease; Type 1/2 diabetes mellitus (HbA1C>8.0%, per medical history questioning or records) ); Asthma; Cerebrovascular disease; Cystic fibrosis, uncontrolled hypertension that does not respond to therapy, Pulmonary fibrosis, Thalassemia.
- Anticipating the need for immunosuppressive treatment within the next 6 months.
- Clinically significant (by means of potentially risking the subject or that would be potentially detrimental to the results of the study) medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health or for severe COVID-19, per the investigator.
- Any progressive or severe neurologic condition/disorder, dementia, seizure disorder, or history of Guillian-Barré syndrome.
- Known or suspected impairment of the immune system including rheumatic, connective tissue or vascular disease of autoimmune origin
- Women who are pregnant or breastfeeding.
- Positive urine or serum pregnancy test or women have an intention to be pregnant during the study.
- Clinically significant abnormal CBC results in WBC, hemoglobin, hematocrit, or platelets.
- Clinically significant abnormal urinalysis: RBC, protein, or glucose only.
- Positive serology for: hepatitis B surface antigen, hepatitis C, HIV.
- Known or suspected illness caused by coronaviruses, SARS-CoV 1, and Middle East Respiratory Syndrome (MERS)-CoV..
- Received any prior vaccine against a coronavirus.
- Receipt of blood/plasma products or immunoglobulin, from within 60 days before study intervention administration or planned receipt throughout the study.
- Immunosuppressive medications received within 90 days before screening. (Not including [1] corticosteroid nasal spray for allergic rhinitis; [2] topical corticosteroids for mild, uncomplicated dermatitis; or [3] oral/parenteral corticosteroids given for non-chronic conditions not expected to recur [length of therapy 10 days or less with completion at least 30 days prior to vaccination].)
- History of alcohol or drug abuse per clinical judgement within 5 years prior to study vaccination (excluding cannabis)
- Participants who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol.
- Any other significant finding that in the opinion of the investigator would increase the risk of the individual having an adverse outcome from participating in this study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: phase I - Group Ia, prime, low dose
Male and female subjects (18-55 years old) administered with a single-dose of IIBR-100 1*10E5 pfu/ml or saline placebo at day 0
|
Single administration of IIBR-100 1*10E5 pfu/ml
Single administration of saline placebo
|
Experimental: phase I - Group Ib, Prime, medium dose
Male and female subjects (18-55 years old) administered with a single-dose of IIBR-100 1*10E6 pfu/ml or saline placebo at day 0
|
Single administration of saline placebo
Single administration of IIBR-100 1*10E6 pfu/ml
|
Experimental: phase I - Group Ic, Prime, high dose
Male and female subjects (18-55 years old) administered with a single-dose of IIBR-100 1*10E7 pfu/ml or saline placebo at day 0
|
Single administration of saline placebo
Single administration of IIBR-100 1*10E7 pfu/ml
|
Experimental: phase I - Group Id, prime-boost, low dose
Male and female subjects (18-55 years old) administered twice with IIBR-100 1*10E5 pfu/ml or saline placebo, 4 weeks apart, at days 0 and 28.
|
Two administrations of IIBR-100 1*10E5 pfu/ml, 28 days apart
Two administrations of saline placebo, 28 days apart
|
Experimental: phase II - Group IIi, prime-boost, medium dose
Male and female subjects (18-55 years old) administered twice with IIBR-100 1*10E6 pfu/ml or saline placebo, 4 weeks apart at days 0 and 28.
|
Two administrations of saline placebo, 28 days apart
Two administrations of IIBR-100 1*10E6 pfu/ml, 28 days apart
|
Experimental: phase II - Group IIj, prime-boost, medium dose, elderly subjects
Male and female subjects (56-85 years old) administered twice with IIBR-100 1*10E6 pfu/ml or saline placebo, 4 weeks apart, at days 0 and 28.
|
Two administrations of saline placebo, 28 days apart
Two administrations of IIBR-100 1*10E6 pfu/ml, 28 days apart
|
Experimental: phase II - Group IIk, prime-boost, high dose
Male and female subjects (18-55 years old) administered twice with IIBR-100 1*10E7 pfu/ml or saline placebo, 4 weeks apart at days 0 and 28.
|
Two administrations of saline placebo, 28 days apart
Two administrations of IIBR-100 1*10E7 pfu/ml, 28 days apart
|
Experimental: phase II - Group IIl, prime-boost, high dose, elderly subjects
Male and female subjects (56-85 years old) administered twice with IIBR-100 1*10E7 pfu/ml or saline placebo, 4 weeks apart, at days 0 and 28.
|
Two administrations of saline placebo, 28 days apart
Two administrations of IIBR-100 1*10E7 pfu/ml, 28 days apart
|
Experimental: phase II - Group IIm, prime-boost, top dose
Male and female subjects (18-55 years old) administered twice with IIBR-100 1*10E8 pfu/ml or saline placebo, 4 weeks apart at days 0 and 28.
|
Two administrations of saline placebo, 28 days apart
Two administrations of IIBR-100 1*10E8 pfu/ml, 28 days apart
|
Experimental: phase II - Group IIn, prime-boost, top dose, elderly subjects
Male and female subjects (56-85 years old) administered twice with IIBR-100 1*10E8 pfu/ml or saline placebo, 4 weeks apart, at days 0 and 28.
|
Two administrations of saline placebo, 28 days apart
Two administrations of IIBR-100 1*10E8 pfu/ml, 28 days apart
|
Experimental: phase II - Group IIa, prime, low dose*
Male and female subjects (18-55 years old) administered with a single-dose of IIBR-100 1*10E5 pfu/ml or saline placebo at day 0. *Treatment arm was deactivated based on immunogenicity data and DSMB recommendations. |
Single administration of IIBR-100 1*10E5 pfu/ml
Single administration of saline placebo
|
Experimental: Phase II - Group IIb, Prime, low dose, elderly subjects*
Male and female subjects (56-85 years old) administered with a single-dose of IIBR-100 1*10E5 pfu/ml or saline placebo at day 0. *Treatment arm was deactivated based on immunogenicity data and DSMB recommendations. |
Single administration of IIBR-100 1*10E5 pfu/ml
Single administration of saline placebo
|
Experimental: phase II - Group IIc, Prime, medium dose*
Male and female subjects (18-55 years old) administered with a single-dose of IIBR-100 1*10E6 pfu/ml or saline placebo at day 0. *Treatment arm was deactivated based on immunogenicity data and DSMB recommendations. |
Single administration of saline placebo
Single administration of IIBR-100 1*10E6 pfu/ml
|
Experimental: phase II - Group IId, Prime, medium dose, elderly subjects*
Male and female subjects (56-85 years old) administered with a single-dose of IIBR-100 1*10E6 pfu/ml or saline placebo at day 0. *Treatment arm was deactivated based on immunogenicity data and DSMB recommendations. |
Single administration of saline placebo
Single administration of IIBR-100 1*10E6 pfu/ml
|
Experimental: Phase II - Group IIe, prime, high dose*
Male and female subjects (18-55 years old) administered with a single-dose of IIBR-100 1*10E7 pfu/ml or saline placebo at day 0. *Treatment arm was deactivated based on immunogenicity data and DSMB recommendations. |
Single administration of saline placebo
Single administration of IIBR-100 1*10E7 pfu/ml
|
Experimental: Phase II - Group IIf, Prime, high dose, elderly subjects*
Male and female subjects (56-85 years old) administered with a single-dose of IIBR-100 1*10E7 pfu/ml or saline placebo at day 0. *Treatment arm was deactivated based on immunogenicity data and DSMB recommendations. |
Single administration of saline placebo
Single administration of IIBR-100 1*10E7 pfu/ml
|
Experimental: phase II - Group IIg, prime-boost, low dose*
Male and female subjects (18-55 years old) administered twice with IIBR-100 1*10E5 pfu/ml or saline placebo, 4 weeks apart at days 0 and 28. *Treatment arm was deactivated based on immunogenicity data and DSMB recommendations. |
Two administrations of IIBR-100 1*10E5 pfu/ml, 28 days apart
Two administrations of saline placebo, 28 days apart
|
Experimental: phase II - Group IIh, prime-boost, low dose, elderly subjects*
Male and female subjects (56-85 years old) administered twice with IIBR-100 1*10E5 pfu/ml or saline placebo, 4 weeks apart, at days 0 and 28. *Treatment arm was deactivated based on immunogenicity data and DSMB recommendations. |
Two administrations of IIBR-100 1*10E5 pfu/ml, 28 days apart
Two administrations of saline placebo, 28 days apart
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I and II - The number, grade and percentage of study participants who experience any study injection-associated AEs or SAEs.
Time Frame: 365 days post last vaccination
|
|
365 days post last vaccination
|
Phase II - IIBR-100 Immunogenicity by determining neutralizing antibody titers to SARS-CoV-2
Time Frame: 28 days post last vaccination
|
Immunogenicity will be determined by GMT, GMFR, Seroconversion rates of the neutralizing antibody titers to SARS-CoV-2 per group at 28 days following last vaccination (in relation to Day 0-baseline).
|
28 days post last vaccination
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I and II - Cellular immunogenicity as assessed by ELISPOT and ELISA.
Time Frame: 365 days post last vaccination
|
Cellular immunogenicity will be assessed at the following days: 0, 28±4d, 56±5d, 84±4d, 168±14d and 365±14d for single dose groups and at days 0, 56±5d, 84±4d, 112±14d, 196±14d and 393±14d for the prime-boost groups.
|
365 days post last vaccination
|
Phase I and II - IIBR-100 Immunogenicity as determined by GMT, GMFR, Seroconversion rates of the neutralizing antibody titers to SARS-CoV-2 at baseline (day 0) and throughout the study
Time Frame: 365 days post last vaccination
|
Immunogenicity will be evaluated at the following days: 0, 7±2d, 14±2d, 28±4d, 56±5d, 84±4d, 168±14d, 252±14d and 365±14d after the first vaccination for single-dose groups (prime), and at days 0, 14±2d, 28±4d, 35±4d, 42±4d, 56±5d, 84±4d, 112±14d, 196±14d, 280±14d and 393±14d for the prime-boost groups
|
365 days post last vaccination
|
Phase I and II - IIBR-100 immunogenicity as determined by GMT, GMFR, Seroconversion rates of the binding antibody titers to SARS-CoV-2 at baseline (day 0) and throughout the study
Time Frame: 365 days post last vaccination
|
Immunogenicity will be evaluated at the following days: 0, 7±2d, 14±2d, 28±4d, 56±5d, 84±4d, 168±14d, 252±14d and 365±14d after the first vaccination for single-dose groups (prime), and at days 0, 14±2d, 28±4d, 35±4d, 42±4d, 56±5d, 84±4d, 112±14d, 196±14d, 280±14d and 393±14d for the prime-boost groups
|
365 days post last vaccination
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I and II - Potential efficacy of IIBR-100 vaccine by means of prevention of COVID-19 disease (as defined by FDA Guidance)
Time Frame: 14 days post last vaccination
|
Number of virologically confirmed (PCR positive) symptomatic cases of COVID-19, 14 days after having received on or two active vaccine injections
|
14 days post last vaccination
|
Phase I and II - Potential efficacy of IIBR-100 vaccine by means of prevention of COVID-19 Severe Disease (per FDA Guidance)
Time Frame: 14 days post last vaccination
|
Number of virologically confirmed (PCR positive) severe cases of COVID-19, 14 days after having received on or two active vaccine injections
|
14 days post last vaccination
|
Phase I and II - Potential efficacy of IIBR-100 vaccine by means of serology confirmed infection (seroconversion to non-vaccine antigen) in combination with one or more of the clinical symptoms proposed.
Time Frame: 14 days post last vaccination
|
Number of serology confirmed symptomatic cases of COVID-19, 14 days after having received on or two active vaccine injections
|
14 days post last vaccination
|
Phase I and II - Kinetics evaluation of antibody decline based on temporal sub-group analyses
Time Frame: 365 days
|
Kinetics of antibody decline based on temporal sub-group analyses (at 3, 6, 9, 12 months post first vaccination)
|
365 days
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- IIBR 20-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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