Covid19Phase 1/2NCT04608305
Evaluate the Safety, Immunogenicity and Potential Efficacy of an rVSV-SARS-CoV-2-S Vaccine
A Phase 1/2 study testing IIBR-100, low dose (prime), IIBR-100 medium dose (prime) and IIBR-100 high-dose (prime) in people with Covid19, run by Israel Institute for Biological Research (IIBR) at 8 sites in Israel.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Covid19
- What is being tested?
- IIBR-100, low dose (prime), IIBR-100 medium dose (prime) and IIBR-100 high-dose (prime)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 843 participants
- Where
- 8 sitesIsrael
- Study dates
- 28 Oct 2020to 3 Oct 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Israel8 sites
Assuta - University Hospital
Ashdod
Barzilai MC
Ashkelon
Rambam MC
Haifa
Hadassah Medical Center
Jerusalem, 91120
Meir MC
Kfar Saba
Rabin MC
Petah Tikva
Sheba Medical Center Hospital- Tel Hashomer
Ramat Gan, 52621
Sourasky MC
Tel Aviv
About this study
Official title: 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.
Read more
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.
Read the detailed description
In the Phase I, healthy adult volunteers will be randomly allocated to one of the four treatment groups to receive a single administration (prime) of IIBR-100 at low, mid or high dose or saline or two administrations (prime-boost) of IIBR-100 at low dose, or saline, 28 days apart. During Phase I, dosing of prime will proceed in a sequential fashion followed by a safety review committee and DSMB to consider expansion to include the rest of the group and escalation to the next groups. Only Groups that demonstrate acceptable safety profile, immunogenicity and potential efficacy will be included in the Phase II operation. In both phases, the subjects will receive an intramuscular injection of the IIBR-100 consisted of 1ml replicating viral rVSV SARS-CoV-2-S vaccine or placebo consisted of 1ml of 0.9% saline. Dosing will be performed at Day 0 and Day 28 (for allocated to prime-boost treatment groups) in the deltoid muscle and will be followed through 12 months post last vaccination. Follow-up visits for subjects administered with the single administration (prime) or placebo will occur at 1, 2 and 4 weeks as well as 2, 3, 6, 9 and 12 months after dosing. Follow up visits for subjects administered with two administrations (prime-boost) or placebo will occur at 1, 2 and 4 weeks post each vaccination as well as at 2, 3, 6, 9 and 12 months after the second vaccination. Reactogenicity will be measured by the occurrence of solicited injection site and systemic reactions from the time of each dosing through 7 days post each dosing. Unsolicited non-serious safety events will be collected from the time of each dosing through 28 days post each dosing. Serious safety events, new-onset chronic medical conditions and medically attended safety events will be collected through 12 months after the last dosing.
- Conditions
- Covid19
- Being tested
- IIBR-100, low dose (prime), IIBR-100 medium dose (prime), IIBR-100 high-dose (prime), IIBR-100 low-dose (prime-boost), Saline Placebo (single)
- Keywords
- SARS-CoV-2, Vaccine
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IIBR-100, low dose (prime)Biological
Single administration of IIBR-100 1*10E5 pfu/ml
IIBR-100 medium dose (prime)Biological
Single administration of IIBR-100 1*10E6 pfu/ml
IIBR-100 high-dose (prime)Biological
Single administration of IIBR-100 1*10E7 pfu/ml
IIBR-100 low-dose (prime-boost)Biological
Two administrations of IIBR-100 1*10E5 pfu/ml, 28 days apart
Saline Placebo (single)Other
Single administration of saline placebo
Saline Placebo (double)Other
Two administrations of saline placebo, 28 days apart
IIBR-100 medium-dose (prime-boost)Biological
Two administrations of IIBR-100 1*10E6 pfu/ml, 28 days apart
IIBR-100 high-dose (prime-boost)Biological
Two administrations of IIBR-100 1*10E7 pfu/ml, 28 days apart
IIBR-100 top-dose (prime-boost)Biological
Two administrations of IIBR-100 1*10E8 pfu/ml, 28 days apart
| Study group | Role | What they receive |
|---|---|---|
| phase I - Group Ia, prime, low dose | Experimental | 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 Receives: Biological: IIBR-100, low dose (prime); Other: Saline Placebo (single) |
| phase I - Group Ib, Prime, medium dose | Experimental | 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 Receives: Biological: IIBR-100 medium dose (prime); Other: Saline Placebo (single) |
| phase I - Group Ic, Prime, high dose | Experimental | 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 Receives: Biological: IIBR-100 high-dose (prime); Other: Saline Placebo (single) |
| phase I - Group Id, prime-boost, low dose | Experimental | 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. Receives: Biological: IIBR-100 low-dose (prime-boost); Other: Saline Placebo (double) |
| phase II - Group IIa, prime, low dose* | Experimental | 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. Receives: Biological: IIBR-100, low dose (prime); Other: Saline Placebo (single) |
| Phase II - Group IIb, Prime, low dose, elderly subjects* | Experimental | 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. Receives: Biological: IIBR-100, low dose (prime); Other: Saline Placebo (single) |
| phase II - Group IIc, Prime, medium dose* | Experimental | 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. Receives: Biological: IIBR-100 medium dose (prime); Other: Saline Placebo (single) |
| phase II - Group IId, Prime, medium dose, elderly subjects* | Experimental | 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. Receives: Biological: IIBR-100 medium dose (prime); Other: Saline Placebo (single) |
| Phase II - Group IIe, prime, high dose* | Experimental | 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. Receives: Biological: IIBR-100 high-dose (prime); Other: Saline Placebo (single) |
| Phase II - Group IIf, Prime, high dose, elderly subjects* | Experimental | 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. Receives: Biological: IIBR-100 high-dose (prime); Other: Saline Placebo (single) |
| phase II - Group IIg, prime-boost, low dose* | Experimental | 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. Receives: Biological: IIBR-100 low-dose (prime-boost); Other: Saline Placebo (double) |
| phase II - Group IIh, prime-boost, low dose, elderly subjects* | Experimental | 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. Receives: Biological: IIBR-100 low-dose (prime-boost); Other: Saline Placebo (double) |
| phase II - Group IIi, prime-boost, medium dose | Experimental | 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. Receives: Other: Saline Placebo (double); Biological: IIBR-100 medium-dose (prime-boost) |
| phase II - Group IIj, prime-boost, medium dose, elderly subjects | Experimental | 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. Receives: Other: Saline Placebo (double); Biological: IIBR-100 medium-dose (prime-boost) |
| phase II - Group IIk, prime-boost, high dose | Experimental | 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. Receives: Other: Saline Placebo (double); Biological: IIBR-100 high-dose (prime-boost) |
| phase II - Group IIl, prime-boost, high dose, elderly subjects | Experimental | 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. Receives: Other: Saline Placebo (double); Biological: IIBR-100 high-dose (prime-boost) |
| phase II - Group IIm, prime-boost, top dose | Experimental | 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. Receives: Other: Saline Placebo (double); Biological: IIBR-100 top-dose (prime-boost) |
| phase II - Group IIn, prime-boost, top dose, elderly subjects | Experimental | 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. Receives: Other: Saline Placebo (double); Biological: IIBR-100 top-dose (prime-boost) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I and II - The number, grade and percentage of study participants who experience any study injection-associated AEs or SAEs.
- Solicited events for 7 days after vaccination.
- Unsolicited events through 28 days after vaccination.
- SAEs 365 days after last vaccination
- New Onset Chronic Medical Condition (NOCMC) or Medically Attended AE (MAAE) 365 days after last vaccination.
Measured: 365 days post last vaccination
Phase II - IIBR-100 Immunogenicity by determining neutralizing antibody titers to SARS-CoV-2
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).
Measured: 28 days post last vaccination
Secondary outcomes (3)
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
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
Measured: 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
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
Measured: 365 days post last vaccination
Phase I and II - Cellular immunogenicity as assessed by ELISPOT and ELISA.
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.
Measured: 365 days post last vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2020
- Study start28 Oct 2020
- Primary completion3 Oct 2022
- Study completion3 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- The study is comprised of two phases, a dose-escalation Phase I (sentinels + expansions) and expansion to Phase II that includes larger cohorts, elderly age groups and additional boost injection. Subjects will be randomly allocated to the study groups in both phases. Dosing of prime during phase I occurred in a sequential fashion (partially overlapping), starting from low-dose and continuing to mid and high doses following safety reviews. Prior to expansion to phase II, cumulative data from phase I was evaluated (dose and regimen) by the data safety monitoring board. The DSMB's recommendations regarding expansion to phase II were the continuation of prime-boost regimens of medium, high and top doses.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 843 participants (actual)
Sponsor and investigators
- Lead sponsor
- Israel Institute for Biological Research (IIBR)
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04608305
- Sponsor's protocol ID
- IIBR 20-001
- Status last verified
- Nov 2023
- First submitted
- 26 Oct 2020
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Caraco Y, Madar-Balakirski N, Ben-Ami E, Zeltser D, Maayan S, Eliakim-Raz N, Peer A, Brosh-Nissimov T, Vishlitzky V, Beth-Din A, Bar-Haim E, Israely T, Paran N, Fisher M, Hoggeg M, Atsmon J, Cohen D, Goldstaub D, Levin Y, Danon Y, Panet A, Shapira S, Yitzhaki S, Marcus H. Using the vesicular stomatitis virus vector (rVSV vector) platform for SARS-CoV-2 vaccine development: Phase 1/2 safety and immunogenicity of IIBR-100 in healthy adults. Vaccine. 2025 Nov 20;67:127837. doi: 10.1016/j.vaccine.2025.127837. Epub 2025 Oct 16.
PubMed 41106035
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04608305
- Acronym / sponsor ID
- IIBR 20-001
- Conditions
- Covid19
- Keywords
- SARS-CoV-2, Vaccine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 843 participants (actual)
- Lead sponsor
- Israel Institute for Biological Research (IIBR)Other government
- Study start
- 28 Oct 2020 (actual)
- Primary completion
- 3 Oct 2022 (actual)
- Study completion
- 3 Oct 2022 (actual)
- First posted
- 29 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In the Phase I, healthy adult volunteers will be randomly allocated to one of the four treatment groups to receive a single administration (prime) of IIBR-100 at low, mid or high dose or saline or two administrations (prime-boost) of IIBR-100 at low dose, or saline, 28 days apart. During Phase I, dosing of prime will proceed in a sequential fashion followed by a safety review committee and DSMB to consider expansion to include the rest of the group and escalation to the next groups. Only Groups that demonstrate acceptable safety profile, immunogenicity and potential efficacy will be included in the Phase II operation. In both phases, the subjects will receive an intramuscular injection of the IIBR-100 consisted of 1ml replicating viral rVSV SARS-CoV-2-S vaccine or placebo consisted of 1ml of 0.9% saline. Dosing will be performed at Day 0 and Day 28 (for allocated to prime-boost treatment groups) in the deltoid muscle and will be followed through 12 months post last vaccination. Follow-up visits for subjects administered with the single administration (prime) or placebo will occur at 1, 2 and 4 weeks as well as 2, 3, 6, 9 and 12 months after dosing. Follow up visits for subjects administered with two administrations (prime-boost) or placebo will occur at 1, 2 and 4 weeks post each vaccination as well as at 2, 3, 6, 9 and 12 months after the second vaccination. Reactogenicity will be measured by the occurrence of solicited injection site and systemic reactions from the time of each dosing through 7 days post each dosing. Unsolicited non-serious safety events will be collected from the time of each dosing through 28 days post each dosing. Serious safety events, new-onset chronic medical conditions and medically attended safety events will be collected through 12 months after the last dosing.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 18
- Model description
- The study is comprised of two phases, a dose-escalation Phase I (sentinels + expansions) and expansion to Phase II that includes larger cohorts, elderly age groups and additional boost injection. Subjects will be randomly allocated to the study groups in both phases. Dosing of prime during phase I occurred in a sequential fashion (partially overlapping), starting from low-dose and continuing to mid and high doses following safety reviews. Prior to expansion to phase II, cumulative data from phase I was evaluated (dose and regimen) by the data safety monitoring board. The DSMB's recommendations regarding expansion to phase II were the continuation of prime-boost regimens of medium, high and top doses.
| Arm | Type | Receives |
|---|---|---|
| phase I - Group Ia, prime, low dose | Experimental | Biological: IIBR-100, low dose (prime), Other: Saline Placebo (single)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 |
| phase I - Group Ib, Prime, medium dose | Experimental | Biological: IIBR-100 medium dose (prime), Other: Saline Placebo (single)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 |
| phase I - Group Ic, Prime, high dose | Experimental | Biological: IIBR-100 high-dose (prime), Other: Saline Placebo (single)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 |
| phase I - Group Id, prime-boost, low dose | Experimental | Biological: IIBR-100 low-dose (prime-boost), Other: Saline Placebo (double)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. |
| phase II - Group IIa, prime, low dose* | Experimental | Biological: IIBR-100, low dose (prime), Other: Saline Placebo (single)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. |
| Phase II - Group IIb, Prime, low dose, elderly subjects* | Experimental | Biological: IIBR-100, low dose (prime), Other: Saline Placebo (single)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. |
| phase II - Group IIc, Prime, medium dose* | Experimental | Biological: IIBR-100 medium dose (prime), Other: Saline Placebo (single)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. |
| phase II - Group IId, Prime, medium dose, elderly subjects* | Experimental | Biological: IIBR-100 medium dose (prime), Other: Saline Placebo (single)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. |
| Phase II - Group IIe, prime, high dose* | Experimental | Biological: IIBR-100 high-dose (prime), Other: Saline Placebo (single)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. |
| Phase II - Group IIf, Prime, high dose, elderly subjects* | Experimental | Biological: IIBR-100 high-dose (prime), Other: Saline Placebo (single)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. |
| phase II - Group IIg, prime-boost, low dose* | Experimental | Biological: IIBR-100 low-dose (prime-boost), Other: Saline Placebo (double)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. |
| phase II - Group IIh, prime-boost, low dose, elderly subjects* | Experimental | Biological: IIBR-100 low-dose (prime-boost), Other: Saline Placebo (double)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. |
| phase II - Group IIi, prime-boost, medium dose | Experimental | Other: Saline Placebo (double), Biological: IIBR-100 medium-dose (prime-boost)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. |
| phase II - Group IIj, prime-boost, medium dose, elderly subjects | Experimental | Other: Saline Placebo (double), Biological: IIBR-100 medium-dose (prime-boost)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. |
| phase II - Group IIk, prime-boost, high dose | Experimental | Other: Saline Placebo (double), Biological: IIBR-100 high-dose (prime-boost)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. |
| phase II - Group IIl, prime-boost, high dose, elderly subjects | Experimental | Other: Saline Placebo (double), Biological: IIBR-100 high-dose (prime-boost)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. |
| phase II - Group IIm, prime-boost, top dose | Experimental | Other: Saline Placebo (double), Biological: IIBR-100 top-dose (prime-boost)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. |
| phase II - Group IIn, prime-boost, top dose, elderly subjects | Experimental | Other: Saline Placebo (double), Biological: IIBR-100 top-dose (prime-boost)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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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.
Key exclusion criteria (42 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IIBR-100, low dose (prime)Single administration of IIBR-100 1*10E5 pfu/ml | Biological | Phase II - Group IIb, Prime, low dose, elderly subjects*, phase I - Group Ia, prime, low dose, phase II - Group IIa, prime, low dose* |
| IIBR-100 medium dose (prime)Single administration of IIBR-100 1*10E6 pfu/ml | Biological | phase I - Group Ib, Prime, medium dose, phase II - Group IIc, Prime, medium dose*, phase II - Group IId, Prime, medium dose, elderly subjects* |
| IIBR-100 high-dose (prime)Single administration of IIBR-100 1*10E7 pfu/ml | Biological | Phase II - Group IIe, prime, high dose*, Phase II - Group IIf, Prime, high dose, elderly subjects*, phase I - Group Ic, Prime, high dose |
| IIBR-100 low-dose (prime-boost)Two administrations of IIBR-100 1*10E5 pfu/ml, 28 days apart | Biological | phase I - Group Id, prime-boost, low dose, phase II - Group IIg, prime-boost, low dose*, phase II - Group IIh, prime-boost, low dose, elderly subjects* |
| Saline Placebo (single)Single administration of saline placebo | Other | Phase II - Group IIb, Prime, low dose, elderly subjects*, Phase II - Group IIe, prime, high dose*, Phase II - Group IIf, Prime, high dose, elderly subjects*, phase I - Group Ia, prime, low dose, phase I - Group Ib, Prime, medium dose, phase I - Group Ic, Prime, high dose, phase II - Group IIa, prime, low dose*, phase II - Group IIc, Prime, medium dose*, phase II - Group IId, Prime, medium dose, elderly subjects* |
| Saline Placebo (double)Two administrations of saline placebo, 28 days apart | Other | phase I - Group Id, prime-boost, low dose, phase II - Group IIg, prime-boost, low dose*, phase II - Group IIh, prime-boost, low dose, elderly subjects*, phase II - Group IIi, prime-boost, medium dose, phase II - Group IIj, prime-boost, medium dose, elderly subjects, phase II - Group IIk, prime-boost, high dose, phase II - Group IIl, prime-boost, high dose, elderly subjects, phase II - Group IIm, prime-boost, top dose, phase II - Group IIn, prime-boost, top dose, elderly subjects |
| IIBR-100 medium-dose (prime-boost)Two administrations of IIBR-100 1*10E6 pfu/ml, 28 days apart | Biological | phase II - Group IIi, prime-boost, medium dose, phase II - Group IIj, prime-boost, medium dose, elderly subjects |
| IIBR-100 high-dose (prime-boost)Two administrations of IIBR-100 1*10E7 pfu/ml, 28 days apart | Biological | phase II - Group IIk, prime-boost, high dose, phase II - Group IIl, prime-boost, high dose, elderly subjects |
| IIBR-100 top-dose (prime-boost)Two administrations of IIBR-100 1*10E8 pfu/ml, 28 days apart | Biological | phase II - Group IIm, prime-boost, top dose, phase II - Group IIn, prime-boost, top dose, elderly subjects |
Primary outcome
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
* Solicited events for 7 days after vaccination. * Unsolicited events through 28 days after vaccination. * SAEs 365 days after last vaccination * New Onset Chronic Medical Condition (NOCMC) or Medically Attended AE (MAAE) 365 days after 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).
3 secondary outcomes
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
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
Phase I and II - Cellular immunogenicity as assessed by ELISPOT and ELISA.
Time frame: 365 days post last vaccination
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Derived from this study: PubMed 41106035Caraco Y, Madar-Balakirski N, Ben-Ami E, Zeltser D, Maayan S, Eliakim-Raz N, Peer A, Brosh-Nissimov T, Vishlitzky V, Beth-Din A, Bar-Haim E, Israely T, Paran N, Fisher M, Hoggeg M, Atsmon J, Cohen D, Goldstaub D, Levin Y, Danon Y, Panet A, Shapira S, Yitzhaki S, Marcus H. Using the vesicular stomatitis virus vector (rVSV vector) platform for SARS-CoV-2 vaccine development: Phase 1/2 safety and immunogenicity of IIBR-100 in healthy adults. Vaccine. 2025 Nov 20;67:127837. doi: 10.1016/j.vaccine.2025.127837. Epub 2025 Oct 16.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IIBR-100, low dose (prime), IIBR-100 medium dose (prime) and IIBR-100 high-dose (prime) in people with Covid19, run by Israel Institute for Biological Research (IIBR) at 8 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04608305, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.