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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

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ClinicalTrials.gov Identifier: NCT05367843
Recruitment Status : Recruiting
First Posted : May 10, 2022
Last Update Posted : July 13, 2022
Sponsor:
Information provided by (Responsible Party):
Speransa Therapeutics

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
SARS-CoV-2 Infection Drug: PRIME-2-CoV_Beta 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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase 1, Dose Ranging Study Assessing the Safety, Tolerability, Immunogenicity of Vaccine Candidate PRIME-2-CoV_Beta, Orf Virus Expressing SARS-CoV-2 Spike and Nucleocapsid Proteins (ORFEUS Study)
Actual Study Start Date : June 20, 2022
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : July 31, 2023

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Number of participants with solicited local reactions at the injection site [ Time Frame: Up to 7 days after first immunization (Day 1 up to 8) ]
    Solicited local reactions are described as pain, erythema/redness and induration/swelling.

  2. Number of participants with solicited local reactions at the injection site [ Time Frame: Up to 7 days after second immunization (Day 29 up to 36) ]
    Solicited local reactions are described as pain, erythema/redness and induration/swelling.

  3. Number of participants with solicited systemic reactions [ Time Frame: 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.

  4. Number of participants with solicited systemic reactions [ Time Frame: 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.

  5. Number of participants who experience at least one unsolicited Treatment-emergent Adverse Event (TEAE) [ Time Frame: Day 1 up to Day 57 ]

Secondary Outcome Measures :
  1. Geometric mean of SARS-CoV-2-specific serum neutralizing titers against ancestral and variant SARS-CoV-2 strains at each time point [ Time Frame: Up to 6 months ]
  2. 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 [ Time Frame: Up to 6 months ]
  3. 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 [ Time Frame: Up to 6 months ]
  4. Geometric Mean Concentration (GMC) of SARS-CoV-2-spike and nucleocapsid-protein specific binding antibody levels from baseline to each subsequent time point [ Time Frame: Up to 6 months ]
  5. Geometric Mean-fold Rise (GMFR) of SARS-CoV-2-spike and nucleocapsid-protein specific binding antibody levels from baseline to each subsequent time point [ Time Frame: Up to 6 months ]
  6. 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 [ Time Frame: Up to 6 months ]
  7. Recommended Phase 2 Dose (RP2D) of PRIME-2-CoV_Beta [ Time Frame: 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.

  8. Safety and tolerability assessed as incidence of changes from baseline in clinical laboratory values, vital Signs, and Electrocardiograms (ECGs) [ Time Frame: Up to 6 months ]
    Endpoint is assessed as a composite of clinical lab values, vital signs, and ECGs.

  9. Number of participants with solicited local reactions at the injection site [ Time Frame: Up to Day 15 ]
    Solicited local reactions are described as pain, erythema/redness and induration/swelling.

  10. Number of participants with solicited systemic reactions [ Time Frame: Up to Day 15 ]
    Solicited systemic reactions are described as nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. 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.
  2. Body mass index (BMI) over 19 kg/m^2 and under 30 kg/m^2 and weight at least 50 kg at study entry.
  3. 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.

  4. 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.
  5. 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.
  6. 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.
  7. Participants who are SARS-CoV-2 vaccine-naïve (applies to vaccine-naïve group of Cohort A only):

    1. 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).
    2. No previous vaccination with any SARS-CoV-2 vaccine (vaccine-naïve group of Cohort A only).
  8. If the participant is a woman of child bearing potential (WOCBP) must:

    1. have a negative beta-human chorionic gonadotropin (hCG)-urine test at Visit 0 and Visit 1.
    2. 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.
    3. agree to require their male partners to use condoms during sexual contact (unless male partners are sterilized or infertile).
    4. confirm that they practiced at least one highly effective form of contraception for the at least 14 days prior to Visit 0.
    5. 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.

  9. 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.
  10. 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:

  1. SARS-CoV-2 nucleic acid amplification test (NAAT)-positive pharyngeal swab within 24 hours before receipt of study vaccine.
  2. Previously NAAT-confirmed COVID-19 within the last 2 months prior to vaccination.
  3. Participants who are taking medications which may prevent or treat COVID-19.
  4. Participants who received convalescent serum or prior therapeutic antibodies against SARS-CoV-2 in a period of 6 months.
  5. 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).
  6. 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).
  7. Any respiratory illness within the past month OR hospitalization >24 hours for any reason within the past month.
  8. 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.
  9. 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.
  10. 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.
  11. Anticipating the need for immunosuppressive treatment within the next 6 months.
  12. 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.

  13. 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.
  14. Receipt of blood/plasma products or immunoglobulin from 60 days before study vaccine administration or planned receipt throughout the study.
  15. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
  16. 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).
  17. Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
  18. History of human immunodeficiency virus (HIV), known seropositivity or active infection with HIV.
  19. 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.

  20. Known history of active or latent tuberculosis (bacillus tuberculosis).
  21. 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.
  22. 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.
  23. 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.
  24. Participants with prolonged exposure to sheep or goats (e.g., shepherds, sheep farmer).
  25. Pregnant and/or nursing women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05367843


Contacts
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Contact: Please call or email +49 69 8700 649 ext 0 info@speransatherapeutics.com
Contact: Ute Klinkhardt, Dr

Locations
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United States, Illinois
Cedar Crosse Research Center Recruiting
Chicago, Illinois, United States, 60607
United States, Missouri
AMR - Center for Pharmaceutical Research - Kansas City Recruiting
Kansas City, Missouri, United States, 64114
Germany
Clinical Research Center Hannover Recruiting
Hanover, Germany, 30625
Ludwig-Maximilians-University Munich (LMU) Recruiting
Munich, Germany, 80802
Sponsors and Collaborators
Speransa Therapeutics
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Responsible Party: Speransa Therapeutics
ClinicalTrials.gov Identifier: NCT05367843    
Other Study ID Numbers: D1701-VrV-101
2021-005219-30 ( EudraCT Number )
First Posted: May 10, 2022    Key Record Dates
Last Update Posted: July 13, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Speransa Therapeutics:
SARS-CoV-2
Coronavirus
COVID-19
PRIME-2-CoV_Beta
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases