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

NCT05367843 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: D1701-VrV-1012021-005219-30
• Study Type: interventional
• Target: 103
• Locations: 2 countries
• Sites: 7

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.

Conditions

SARS-CoV-2 Infection

Keywords

SARS-CoV-2; Coronavirus; COVID-19; PRIME-2-CoV_Beta

Outcome Measures

Primary Outcomes (5)

• Number of participants with solicited local reactions at the injection site

  Solicited local reactions are described as pain, erythema/redness and induration/swelling.

  Up to 7 days after first immunization (Day 1 up to 8)

• Number of participants with solicited local reactions at the injection site

  Solicited local reactions are described as pain, erythema/redness and induration/swelling.

  Up to 7 days after second immunization (Day 29 up to 36)

• Number of participants with solicited systemic reactions

  Solicited systemic reactions are described as nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever.

  Up to 7 days after first immunization (Day 1 up to 8)

• Number of participants with solicited systemic reactions

  Solicited systemic reactions are described as nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever.

  Up to 7 days after second immunization (Day 29 up to 36)

• Number of participants who experience at least one unsolicited Treatment-emergent Adverse Event (TEAE)

  Day 1 up to Day 57

Secondary Outcomes (10)

• 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

Study Arms (3)

A-Cohorts: Pre-vaccinated

EXPERIMENTAL

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 five groups that receive increasing doses of PRIME-2-CoV\_Beta (two doses, 28 days apart).

Drug: PRIME-2-CoV_Beta

A-Cohorts: SARS-CoV-2 Vaccine-naïve

EXPERIMENTAL

Participants aged 18-55 years who are SARS-CoV-2 vaccine-naïve will receive one preferred dose level of PRIME-2-CoV\_Beta that has been identified as optimal in pre-vaccinated A-Cohorts (two doses, 28 days apart).

Drug: PRIME-2-CoV_Beta

B-Cohorts: Pre-vaccinated elderly

EXPERIMENTAL

Elderly participants aged 65-85 years who have been previously vaccinated against COVID-19 with at least two doses of a SARS-CoV-2 mRNA vaccine will be assigned to three groups to receive previously identified doses of PRIME-2-CoV\_Beta (two doses, 28 days apart).

Drug: PRIME-2-CoV_Beta

Interventions

PRIME-2-CoV_Beta DRUG

Intramuscular (IM) injection

A-Cohorts: Pre-vaccinated; A-Cohorts: SARS-CoV-2 Vaccine-naïve; B-Cohorts: Pre-vaccinated elderly

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Body mass index (BMI) over 19 kg/m\^2 and under 32 kg/m\^2 and weight at least 50 kg at study entry.
• 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.
• 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.
• 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.
• Participants who have previously received at least two vaccinations with a licensed SARS-CoV-2 mRNA vaccine (Spikevax/Moderna and/or Comirnaty/Pfizer administered as two-dose primary series with or without booster vaccination\[s\]) with the last vaccination having occurred at least 3 months prior.
• Participants who are SARS-CoV-2 vaccine-naïve (applies to vaccine-naïve group of Cohort A only):
• 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).
• No previous vaccination with any SARS-CoV-2 vaccine (vaccine-naïve group of Cohort A only).
• If the participant is a woman of child bearing potential (WOCBP) must:
• have a negative beta-human chorionic gonadotropin (hCG)-urine test at Visit 0 and Visit 1.
• agree to practice a highly effective form of contraception for at least 14 days prior to study vaccination and continuously until a minimum of 28 days after receiving the last immunization.
• agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study, starting after Visit 0 and continuously until 28 days after receiving the last immunization.
• Note: Women that are postmenopausal or permanently sterilized will be considered as not having reproductive potential.
• 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 from Visit 1 (pre-dose) and continuously until a minimum of 28 days after receiving the last immunization.

You may not qualify if:

• SARS-CoV-2 nucleic acid amplification test (NAAT)-positive pharyngeal swab within 24 hours before receipt of study vaccine.
• Previously NAAT-confirmed COVID-19 within the last 2 months prior to vaccination.
• Participants who are taking medications which may prevent or treat COVID-19.
• Participants who received convalescent serum or prior therapeutic antibodies against SARS-CoV-2 in a period of 6 months.
• 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).
• 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).
• Any respiratory illness deemed clinically relevant by the investigator within the past month OR hospitalization \>24 hours for any reason within the past month.
• History of or current cardiac disease, including but not limited to individuals with uncontrolled hypertension (defined as grade 1 hypertension or higher as per ISH guidelines with or without antihypertensive medication), congenital structural heart diseases, myocarditis and/or pericarditis, coronary heart disease (with/without angina pectoris) or myocardial infarction.
• 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.
• 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 requiring immunosuppressive medication, malignancies; obesity (BMI of 32 or higher); serious heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies; sickle cell disease; insulin-dependent type 2 diabetes mellitus.
• Anticipating the need for immunosuppressive treatment within the next 6 months.
• Any screening hematology and/or blood chemistry laboratory value outside normal range (defined as ≥Grade 1 abnormality) and deemed clinically relevant by the investigator.
• Note: Except bilirubin, participants with any stable Grade 1 abnormalities may be considered eligible at the discretion of the Investigator.
• Chronic immunosuppressive therapy (defined as ≥14 days), including cytotoxic agents, systemic corticosteroids exceeding 10mg/d prednisone equivalent, disease-modifying antirheumatic drugs \[DMARDs\]) or any other immunomodulating agents within the last 3 months or planned receipt throughout the study.
• Note: 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.

Sponsors & Collaborators

• Speransa Therapeutics: lead

Study Sites (7)

Accel Research Sites (ARS) - DeLand Clinical Research Unit

Florida City, Florida, 32720, United States

Location

Cedar Crosse Research Center

Chicago, Illinois, 60607, United States

Location

AMR - Center for Pharmaceutical Research - Kansas City

Kansas City, Missouri, 64114, United States

Location

Caroline Institute for Clinical Research

Fayetteville, North Carolina, 28303, United States

Location

Cedar Health Research - DFW-East

Dallas, Texas, 75251, United States

Location

Clinical Research Center Hannover

Hanover, 30625, Germany

Location

Ludwig-Maximilians-University Munich (LMU)

Munich, 80802, Germany

Location

Related Publications (1)

• Klinkardt U, Schunk M, Ervin J, Schindler C, Sugimoto D, Rankin B, Amann R, Monti M, Kutschenko A, Schumacher C, Huber K, Zeder A, Heikkila N, Didierlaurent AM, Schwarz SE, Derouazi M. A novel orf virus vector-based COVID-19 booster vaccine shows cross-neutralizing activity in the absence of anti-vector neutralizing immunity. Hum Vaccin Immunother. 2024 Dec 31;20(1):2410574. doi: 10.1080/21645515.2024.2410574. Epub 2024 Oct 14.

  PMID: 39397784 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

PRIME-2-CoV_Beta COVID-19 vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: May 10, 2022
• Study Start: June 20, 2022
• Primary Completion: July 18, 2023
• Study Completion: November 8, 2023
• Last Updated: February 9, 2024

Record last verified: 2024-02

Locations

US (5); DE (2)