A Study Assessing the Safety, Tolerability, Immunogenicity of COVID-19 Vaccine Candidate PRIME-2-CoV_Beta, Orf Virus Expressing SARS-CoV_2 Spike and Nucleocapsid Proteins
Study Details
Study Description
Brief Summary
PRIME-2-CoV_Beta is the first clinical candidate based on the attenuated 2nd generation Orf virus (ORFV) vaccine platform which encodes for the structural spike (S)- and nucleocapsid (N) protein of SARS-CoV-2. The aim of the multivalent vaccine is to broaden the specific immune response against SARS-CoV-2 and to increase the probability of cross-protection against emerging variants.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The Phase 1 dose-finding study (ORFEUS) will assess the safety, tolerability and immunogenicity of a two-dose regimen (28-days apart) of PRIME-2-CoV_Beta administered by intramuscular (IM) route in adult participants.
In the first part, the safety and immunogenicity of increasing doses of PRIME-2-CoV_Beta will be assessed in adult healthy participants aged 18 to 55 years who have been either vaccinated against COVID-19 with at least two doses of a SARS-CoV-2 mRNA vaccine (i.e. primary sequence with or without booster vaccination, subsequently referred to as "pre-vaccinated") or are SARS-CoV-2 vaccine-naïve. In addition, two dose levels identified in pre-vaccinated participants will be further evaluated for safety and immunogenicity in pre-vaccinated elderly participants aged 65-85 years (B-cohorts).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort A: Pre-vaccinated Participants aged 18-55 years who have been pre-vaccinated against COVID-19 with at least two doses of a SARS-CoV-2 mRNA vaccine will be assigned to groups that receive increasing doses of PRIME-2-CoV_Beta (two doses, 28 days apart). |
Drug: PRIME-2-CoV_Beta
Intramuscular (IM) injection
|
| Experimental: Cohort A: SARS-CoV-2 Vaccine-naïve Participants aged 18-55 years who are SARS-CoV-2 vaccine naïve will be assigned to groups that receive increasing doses of PRIME-2-CoV_Beta (two doses, 28 days apart). |
Drug: PRIME-2-CoV_Beta
Intramuscular (IM) injection
|
| Experimental: Cohort B: 2 Pre-vaccinated elderly Elderly participants aged 65-85 who have been previously vaccinated against COVID-19 with at least two doses of a SARS-CoV-2 mRNA vaccine will be assigned to two groups to receive a previously identified dose of PRIME-2-CoV_Beta (two doses, 28 days apart). |
Drug: PRIME-2-CoV_Beta
Intramuscular (IM) injection
|
Outcome Measures
Primary Outcome Measures
- Number of participants with solicited local reactions at the injection site [Up to 7 days after first immunization (Day 1 up to 8)]
Solicited local reactions are described as pain, erythema/redness and induration/swelling.
- Number of participants with solicited local reactions at the injection site [Up to 7 days after second immunization (Day 29 up to 36)]
Solicited local reactions are described as pain, erythema/redness and induration/swelling.
- Number of participants with solicited systemic reactions [Up to 7 days after first immunization (Day 1 up to 8)]
Solicited systemic reactions are described as nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever.
- Number of participants with solicited systemic reactions [Up to 7 days after second immunization (Day 29 up to 36)]
Solicited systemic reactions are described as nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever.
- Number of participants who experience at least one unsolicited Treatment-emergent Adverse Event (TEAE) [Day 1 up to Day 57]
Secondary Outcome Measures
- Geometric mean of SARS-CoV-2-specific serum neutralizing titers against ancestral and variant SARS-CoV-2 strains at each time point [Up to 6 months]
- Geometric Mean-fold Rise (GMFR) of SARS-CoV-2-specific serum neutralizing titers against ancestral and variant SARS-CoV-2 strains from baseline to each subsequent timepoint [Up to 6 months]
- Number of participants who achieve ≥ 4-fold rise from baseline in SARS-CoV-2-specific serum neutralizing titers against ancestral and variant SARS-CoV-2 strains from baseline to each subsequent timepoint [Up to 6 months]
- Geometric Mean Concentration (GMC) of SARS-CoV-2-spike and nucleocapsid-protein specific binding antibody levels from baseline to each subsequent time point [Up to 6 months]
- Geometric Mean-fold Rise (GMFR) of SARS-CoV-2-spike and nucleocapsid-protein specific binding antibody levels from baseline to each subsequent time point [Up to 6 months]
- Number of participants who achieve ≥ 4-fold rise in SARS-CoV-2-spike and nucleocapsid-protein specific binding antibody levels from baseline to each subsequent time point [Up to 6 months]
- Recommended Phase 2 Dose (RP2D) of PRIME-2-CoV_Beta [Up to 12 months]
RP2D based on an integrated analysis of overall safety and immunogenicity endpoints (change in SARS-CoV-2-specific serum neutralizing titers and SARS-CoV-2-spike protein-specific and -nucleocapsid protein-specific binding antibody levels.
- Safety and tolerability assessed as incidence of changes from baseline in clinical laboratory values, vital Signs, and Electrocardiograms (ECGs) [Up to 6 months]
Endpoint is assessed as a composite of clinical lab values, vital signs, and ECGs.
- Number of participants with solicited local reactions at the injection site [Up to Day 15]
Solicited local reactions are described as pain, erythema/redness and induration/swelling.
- Number of participants with solicited systemic reactions [Up to Day 15]
Solicited systemic reactions are described as nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female participants between the ages of 18 and 55 years, (A-cohorts), and 65 and 85 years (B-cohorts), inclusive at study entry.
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Body mass index (BMI) over 19 kg/m2 and under 30 kg/m2 and weight at least 50 kg at study entry.
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Healthy participants who are determined by medical history, physical examination, and clinical judgment of the Investigator to be eligible for inclusion in the study.
Note: Healthy participants may have stable pre-existing disease defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment.
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Able to give personal signed informed consent and willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, and other study procedures.
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Participants must agree not to be vaccinated with any SARS-CoV-2 vaccine, starting after Visit 0 and continuously until 6 months after receiving the first study immunization.
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Participants who have previously received at least two vaccinations with SARS-CoV-2 mRNA vaccine (full primary sequence with or without booster vaccination) with the last vaccination having occurred at least 3 months prior.
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Participants who are SARS-CoV-2 vaccine-naïve (applies to vaccine-naïve group of
Cohort A only):
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Currently not working in occupations with high risk of exposure to SARS-CoV-2 (e.g., healthcare worker, emergency response personnel) (vaccine-naïve group of Cohort A only).
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No previous vaccination with any SARS-CoV-2 vaccine (vaccine-naïve group of Cohort A only).
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If the participant is a woman of child bearing potential (WOCBP) must:
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have a negative beta-human chorionic gonadotropin (hCG)-urine test at Visit 0 and Visit 1.
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agree to practice a highly effective form of contraception during the study, starting after Visit 0 and continuously until 30 days after receiving the last immunization.
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agree to require their male partners to use condoms during sexual contact (unless male partners are sterilized or infertile).
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confirm that they practiced at least one highly effective form of contraception for the at least 14 days prior to Visit 0.
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agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study, starting after Visit 0 and continuously until 30 days after receiving the last immunization.
Note: Women that are postmenopausal or permanently sterilized will be considered as not having reproductive potential.
Note: Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective contraceptive methods.
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Men who are sexually active with a WOCBP and have not had a vasectomy must agree to practice a highly effective form of contraception with their female partner during the study, starting after Visit 0 and continuously until 30 days after receiving the last immunization.
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Men must be willing to refrain from sperm donation, starting after Visit 0 and continuously until 30 days after receiving the last immunization.
Exclusion Criteria:
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SARS-CoV-2 nucleic acid amplification test (NAAT)-positive pharyngeal swab within 24 hours before receipt of study vaccine.
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Previously NAAT-confirmed COVID-19 within the last 2 months prior to vaccination.
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Participants who are taking medications which may prevent or treat COVID-19.
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Participants who received convalescent serum or prior therapeutic antibodies against SARS-CoV-2 in a period of 6 months.
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History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the study vaccine(s).
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Current clinical or microbiological diagnosis of COVID-19, including active respiratory or non-respiratory symptoms associated with COVID-19 disease (i.e. symptomatic COVID 19 disease).
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Any respiratory illness within the past month OR hospitalization >24 hours for any reason within the past month.
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History of or current cardiac disease, including but not limited to individuals with chronic hypertension, congenital structural heart diseases, myocarditis and/or pericarditis, coronary heart disease (with/without angina pectoris) or myocardial infarction.
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Individuals with myocarditis after mRNA vaccination, or individuals with AEs after mRNA-vaccination that are in nature and severity beyond the common AEs that can be expected.
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Individuals at high risk for severe COVID-19, including those with any of the following risk factors: cancer; chronic kidney disease; chronic obstructive pulmonary disease (COPD); immunocompromised state (weakened immune system) from solid organ transplant; rheumatologic or autoinflammatory conditions, malignancies; obesity (BMI of 30 or higher); serious heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies; sickle cell disease; type 2 diabetes mellitus.
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Anticipating the need for immunosuppressive treatment within the next 6 months.
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Any screening hematology and/or blood chemistry laboratory value that meets the definition of ≥Grade 1 abnormality.
Note: Except bilirubin, participants with any stable Grade 1 abnormalities may be considered eligible at the discretion of the Investigator.
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Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (or equivalent e.g., disease-modifying antirheumatic drugs [DMARDs]), e.g., for cancer or an autoimmune disease, or planned receipt throughout the study. If systemic corticosteroids have been administered short-term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days before study intervention administration. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
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Receipt of blood/plasma products or immunoglobulin from 60 days before study vaccine administration or planned receipt throughout the study.
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Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
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Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to: systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain-Barré syndrome, multiple sclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell arteritis (temporal arteritis), psoriasis, and insulin dependent diabetes mellitus (type 1).
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Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
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History of human immunodeficiency virus (HIV), known seropositivity or active infection with HIV.
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History of known seropositivity for or evidence of active viral infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
Exception: Participants who are seropositive because of HBV vaccine are eligible. Participants who had HCV but have received an antiviral treatment and show no detectable HCV viral deoxyribonucleic acid (DNA) for 6 months are eligible.
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Known history of active or latent tuberculosis (bacillus tuberculosis).
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Any concomitant serious health condition or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior, which, in the opinion of the Investigator, would place the participant at undue risk from the study.
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Has received a live vaccine within 30 days of planned start of study vaccine. Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines and are NOT allowed 28 days prior to the first dose and 12 weeks after last dose of PRIME-2-CoV_Beta administration.
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If a participant has contraindication to IM injections or received therapeutic anticoagulation for a period of 60 days before vaccination. Note: prophylactic anticoagulation is allowed.
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Participants with prolonged exposure to sheep or goats (e.g., shepherds, sheep farmer).
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Pregnant and/or nursing women.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cedar Crosse Research Center | Chicago | Illinois | United States | 60607 |
| 2 | AMR - Center for Pharmaceutical Research - Kansas City | Kansas City | Missouri | United States | 64114 |
| 3 | Clinical Research Center Hannover | Hanover | Germany | 30625 | |
| 4 | Ludwig-Maximilians-University Munich (LMU) | Munich | Germany | 80802 |
Sponsors and Collaborators
- Speransa Therapeutics
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D1701-VrV-101
- 2021-005219-30