COVID-19Phase 2/3BRILIFE002NCT04990466
Phase 2b/3 Trial of VSV-ΔG SARS-CoV-2 Vaccine (BRILIFE) Against Approved Comparator Vaccine.
A Phase 2/3 study testing IIBR-100 and Active Comparator in people with COVID-19, run by NeuroRx, Inc..
Trial summary
IIBR-100 (VSV-ΔG) is a self-propagating live virus vaccine that contains the spike protein of the Wuhan wild-type SARS-CoV-2 virus. Preclinical and phase 1/2 trials have demonstrated no safety signals of concern and have further demonstrated immunologic response that approximates the response seen in convalescent… Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- COVID-19
- What is being tested?
- IIBR-100 and Active Comparator
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Sep 2021to 28 Feb 2022
- Phase
- Phase 2/3
- 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 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
- No clinically significant abnormalities in hematology, blood chemistry, or urinalysis laboratory tests at screening.
- 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
- 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
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- 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
- 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.
About this study
Official title: A Phase IIb/3 Randomized, Multi-Center, Placebo-Controlled Noninferiority Study to Evaluate the Safety, Immunogenicity and Potential Efficacy of an rVSV-SARS-CoV-2-S Vaccine (IIBR-100) in Adults Compared to an Approved COVID-19 Vaccine
IIBR-100 (VSV-ΔG) is a self-propagating live virus vaccine that contains the spike protein of the Wuhan wild-type SARS-CoV-2 virus. Preclinical and phase 1/2 trials have demonstrated no safety signals of concern and have further demonstrated immunologic response that approximates the response seen in convalescent individuals. The purpose of this phase 2b/3 trial is to document the non-inferiority of IIBR-100 vs. an already-approved vaccine for COVID-19.
Read the detailed description
STUDY RATIONALE:
The SARS-CoV-2 virus is responsible for the COVID-19 pandemic, perhaps the deadliest in 100 years. 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. Early cases have been reported in Israel around February 2020, and at the time this protocol is being drafted. The virus has spread to 190 countries with more than 198 million confirmed cases and more than 4.2 million confirmed deaths as of August 2, 2021 (WHO website https://covid19.who.int/).
In an effort to curb the pandemic, the Israel Institute for Biological Research (IIBR) has developed a replication-competent recombinant VSVΔG-spike vaccine (rVSV-SARS-CoV-2-S, IIBR-100), in which the glycoprotein of VSV is replaced by the spike protein of the SARS-CoV-2 virus. Pre-clinical data suggested IIBR-100 as a safe, efficacious, and protective vaccine against SARS-CoV-2 infection. In addition, clinical experience from over 20,000 subjects vaccinated with Ervebo®, an Ebola vaccine developed by Merck \& Co. and licensed by FDA in 2019, also supports the safety of the VSV-ΔG backbone. An overlapping Phase I/II study in Israel is showing a good safety profile. This study is intended to support late-stage clinical studies and eventual mass immunization of the Georgian population.
STUDY DESIGN:
This is a Phase IIb/3, prospective, randomized, comparator-controlled, observer-blind, multi-center non-inferiority study.
Subjects will receive two intramuscular (IM) injections of the IIBR-100 (prime-boost) separated by 28 days consisted of 1 ml replicating viral rVSV SARS-CoV-2-S vaccine or active comparator. Injection will be performed at Day 0 and Day 28±2d in the deltoid muscle and will be followed through 12 months post last vaccination.
Follow-up (FU) visits will occur 1, 2 and 4 weeks, as well as, 2 ,3, 6, 9, and 12 months post last vaccination.
The primary outcome will be PCR+ infection with COVID-19 six months after vaccination. Key secondary outcome will be serologic immunity.
Reactogenicity will be assessed at these visits, and blood will be drawn for immunogenicity assays. Additional safety and reactogenicity data will be solicited via electronic diary and telephone calls to subjects performed 1 and 2 days post each vaccination.
Reactogenicity will be measured by the occurrence of solicited injection site reaction and systemic reaction from the time of each vaccination through 7 days post each vaccination. Unsolicited non-serious Adverse Events (AEs), Serious adverse events (SAEs), new-onset chronic medical conditions (NOCMCs) and medically-attended adverse events (MAAEs) will be collected through 12 months after the last vaccination.
Clinical safety laboratory evaluations will be performed at screening, as well as immediately prior to and 7 days post each vaccination.
- Conditions
- COVID-19
- Being tested
- IIBR-100, Active Comparator
- Keywords
- COVID-19, SARS-CoV-2, Delta Variant, BRILIFE, VSV-ΔG
- 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-100Drug
Administration of IIBR-100 vaccine
Active ComparatorDrug
Administration of a currently-approved vaccine for COVID-19
| Study group | Role | What they receive |
|---|---|---|
| Active Vaccine | Experimental | IIBR-100 (VSV-ΔG) vaccine at 10 to the 8th strength in prime/boost separated by 28 days Receives: Drug: IIBR-100 |
| Active Comparator | Active comparator | A currently approved vaccine for COVID-19 administered in prime/boost separated by 28 days Receives: Drug: Active Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevention of Serology-confirmed SARS-CoV-2 infection
Prevention of serology confirmed infection (seroconversion to non-vaccine antigen) in Prevention of PCR+ COVID-19 in combination with one or more of the clinical symptoms
Measured: 180 days
Secondary outcomes (4)
Prevention of COVID-19 mild/moderate disease
Prevention of COVID-19 mild/moderate disease
Measured: Beginning 14 days after second injection
Prevention of COVID-19 severe disease
Prevention of COVID-19 severe disease
Measured: Beginning 14 days after second injection
Serologic Immunogenicity
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
Measured: 365 days
Cellular Immunogenicity
Cellular immunogenicity as assessed by ELISPOT and ELISA
Measured: 365 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2021
- Study start30 Sep 2021 (estimated)
- Primary completion31 Dec 2021 (estimated)
- Study completion28 Feb 2022 (estimated)
Why it stopped: Production of the BriLife vaccine was halted by government sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies 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 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind, comparator-controlled non-inferiority trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- NeuroRx, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jonathan C Javitt, MD, MPH, Study chair, NRx Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04990466
- Sponsor's protocol ID
- BriLife_001
- Acronym
- BRILIFE002
- Status last verified
- Jan 2024
- First submitted
- 3 Aug 2021
- Last updated
- 19 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Vaccination dates, baseline serology, and post-vaccination serology/cellular immunity/infection rates will be shared
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIb/3 Randomized, Multi-Center, Placebo-Controlled Noninferiority Study to Evaluate the Safety, Immunogenicity and Potential Efficacy of an rVSV-SARS-CoV-2-S Vaccine (IIBR-100) in Adults Compared to an Approved COVID-19 Vaccine
- ClinicalTrials.gov ID
- NCT04990466
- Acronym / sponsor ID
- BRILIFE002 / BriLife_001
- Conditions
- COVID-19
- Keywords
- COVID-19, SARS-CoV-2, Delta Variant, BRILIFE, VSV-ΔG
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Production of the BriLife vaccine was halted by government sponsor
- Enrolment
- 0 participants (actual)
- Lead sponsor
- NeuroRx, Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Sep 2021 (estimated)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 28 Feb 2022 (estimated)
- First posted
- 4 Aug 2021 (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.
IIBR-100 (VSV-ΔG) is a self-propagating live virus vaccine that contains the spike protein of the Wuhan wild-type SARS-CoV-2 virus. Preclinical and phase 1/2 trials have demonstrated no safety signals of concern and have further demonstrated immunologic response that approximates the response seen in convalescent individuals. The purpose of this phase 2b/3 trial is to document the non-inferiority of IIBR-100 vs. an already-approved vaccine for COVID-19.
Detailed description
STUDY RATIONALE:
The SARS-CoV-2 virus is responsible for the COVID-19 pandemic, perhaps the deadliest in 100 years. 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. Early cases have been reported in Israel around February 2020, and at the time this protocol is being drafted. The virus has spread to 190 countries with more than 198 million confirmed cases and more than 4.2 million confirmed deaths as of August 2, 2021 (WHO website https://covid19.who.int/).
In an effort to curb the pandemic, the Israel Institute for Biological Research (IIBR) has developed a replication-competent recombinant VSVΔG-spike vaccine (rVSV-SARS-CoV-2-S, IIBR-100), in which the glycoprotein of VSV is replaced by the spike protein of the SARS-CoV-2 virus. Pre-clinical data suggested IIBR-100 as a safe, efficacious, and protective vaccine against SARS-CoV-2 infection. In addition, clinical experience from over 20,000 subjects vaccinated with Ervebo®, an Ebola vaccine developed by Merck \& Co. and licensed by FDA in 2019, also supports the safety of the VSV-ΔG backbone. An overlapping Phase I/II study in Israel is showing a good safety profile. This study is intended to support late-stage clinical studies and eventual mass immunization of the Georgian population.
STUDY DESIGN:
This is a Phase IIb/3, prospective, randomized, comparator-controlled, observer-blind, multi-center non-inferiority study.
Subjects will receive two intramuscular (IM) injections of the IIBR-100 (prime-boost) separated by 28 days consisted of 1 ml replicating viral rVSV SARS-CoV-2-S vaccine or active comparator. Injection will be performed at Day 0 and Day 28±2d in the deltoid muscle and will be followed through 12 months post last vaccination.
Follow-up (FU) visits will occur 1, 2 and 4 weeks, as well as, 2 ,3, 6, 9, and 12 months post last vaccination.
The primary outcome will be PCR+ infection with COVID-19 six months after vaccination. Key secondary outcome will be serologic immunity.
Reactogenicity will be assessed at these visits, and blood will be drawn for immunogenicity assays. Additional safety and reactogenicity data will be solicited via electronic diary and telephone calls to subjects performed 1 and 2 days post each vaccination.
Reactogenicity will be measured by the occurrence of solicited injection site reaction and systemic reaction from the time of each vaccination through 7 days post each vaccination. Unsolicited non-serious Adverse Events (AEs), Serious adverse events (SAEs), new-onset chronic medical conditions (NOCMCs) and medically-attended adverse events (MAAEs) will be collected through 12 months after the last vaccination.
Clinical safety laboratory evaluations will be performed at screening, as well as immediately prior to and 7 days post each vaccination.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double-blind, comparator-controlled non-inferiority trial
| Arm | Type | Receives |
|---|---|---|
| Active Vaccine | Experimental | Drug: IIBR-100IIBR-100 (VSV-ΔG) vaccine at 10 to the 8th strength in prime/boost separated by 28 days |
| Active Comparator | Active comparator | Drug: Active ComparatorA currently approved vaccine for COVID-19 administered in prime/boost separated by 28 days |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
- No clinically significant abnormalities in hematology, blood chemistry, or urinalysis laboratory tests at screening.
- 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).
Key exclusion criteria (20 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 (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).
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-100Administration of IIBR-100 vaccine | Drug | Active Vaccine |
| Active ComparatorAdministration of a currently-approved vaccine for COVID-19 | Drug | Active Comparator |
Primary outcome
Prevention of Serology-confirmed SARS-CoV-2 infection
Time frame: 180 days
Prevention of serology confirmed infection (seroconversion to non-vaccine antigen) in Prevention of PCR+ COVID-19 in combination with one or more of the clinical symptoms
4 secondary outcomes
Prevention of COVID-19 mild/moderate disease
Time frame: Beginning 14 days after second injection
Prevention of COVID-19 severe disease
Time frame: Beginning 14 days after second injection
Serologic Immunogenicity
Time frame: 365 days
Cellular Immunogenicity
Time frame: 365 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2024.
- Individual participant dataSharing planned: Yes. Vaccination dates, baseline serology, and post-vaccination serology/cellular immunity/infection rates will be shared
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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.
Jonathan C Javitt, MD, MPH study chair
NRx Pharmaceuticals, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing IIBR-100 and Active Comparator in people with COVID-19, run by NeuroRx, Inc..
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 7 inclusion and 20 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: withdrawn, as of the sponsor's last update on 19 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 was withdrawn before enrolling participants, so there are no results.
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?
Prevention of Serology-confirmed SARS-CoV-2 infection (time frame: 180 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Jan 2024.