Safety, Tolerability and Immunogenicinity of a Coronavirus-Like Particle COVID-19 Vaccine in Adults Aged 18-55 Years.

NCT04450004 | Completed Phase 1 DMC

• 1 other identifier: CP-PRO-COVLP-019
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 2

Brief Summary

The study will be a randomized, partially-blinded, prime-boost, staggered dose-escalation Phase 1 study intended to assess the safety, tolerability, and immunogenicity of the Coronavirus-Like Particle COVID-19 Vaccine at three dose levels (3.75 µg, 7.5 µg, and 15 µg VLP) unadjuvanted or adjuvanted with either CpG 1018 or AS03 in healthy adults 18 to 55 years of age, who have been tested for the absence of SARS-CoV-2 antibodies. At each dose level, the vaccine will initially be administered to a small number of subjects. Vaccinations of the first 6 subjects at the lowest dose level will be staggered so that each vaccination must be performed at least 30 minutes apart. Vaccination of the remaining subjects at the same dose level and the next higher vaccine dose level will be administered with approval of the Independent Data Monitoring Committee (IDMC). The same process will be followed for the second vaccine administration. All subjects will be followed for a period of 12 months after the second administration of the vaccine for safety and immunogenicity testing at the end of the follow-up period.

Conditions

SARS-CoV 2

Outcome Measures

Primary Outcomes (8)

• Immediate adverse event (AEs)

  Percentage, intensity, and relationship to vaccination of immediate adverse events (AEs)

  30 minutes

• Solicited local and systemic adverse events (AEs)

  Percentage, intensity, and relationship to vaccination of solicited local and systemic adverse events (AEs) following each vaccination

  7 days

• Unsolicited adverse events (AEs)

  Percentage, intensity, and relationship of unsolicited adverse events (AEs) following each vaccine administration

  21 days

• Serious adverse events (SAEs), adverse events (AEs) leading to withdrawal, adverse event of special interest (AESI) (including vaccine-enhanced disease) and deaths

  Occurrences of serious adverse events (SAEs), adverse events (AEs) leading to withdrawal, adverse event of special interest (AESIs) (including vaccine-enhanced disease (VED)), and deaths following each vaccine administration

  21 days

• Safety labs

  Number and percentage of subjects with normal and abnormal clinically significant urine, haematological and biochemical values prior to and 3 days following each vaccination.

  3 days

• Neutralizing antibody (Nab assay) response

  Nab response induced by the vaccine against the SARS-CoV-2 virus

  21 days

• Specific Th1 cell-mediated immunity (CMI) response

  Cell-mediated immunity (CMI) response induced by the vaccine against the SARS-CoV-2 virus after each vaccination, as measured by Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot)

  21 days

• Specific Th2 cell-mediated immunity (CMI) response

  Cell-mediated immunity (CMI) response induced by the vaccine against the SARS-CoV-2 virus after each vaccination, as measured by Interleukin-4 (IL-4) ELISpot

  21 days

Secondary Outcomes (5)

• Serious adverse events (SAEs), adverse events (AEs) leading to withdrawal, adverse event of special interest (AESI) (including vaccine-enhanced disease) and deaths

  Day 42 to 386

• Specific antibody response induced by the vaccine against the SARS-CoV-2 virus measured by total IgG and/or IgM levels

  Day 21, 42, 201 and 386

• Neutralizing antibody (Nab assay) response induced by the treatment groups against the SARS-CoV-2 virus

  Day 201 and 386

• Specific Th1 cell-mediated immunity (CMI) response induced by the vaccine against the SARS-CoV-2 virus

  Day 201 and 386

• Specific Th2 cell-mediated immunity (CMI) response induced by the vaccine against the SARS-CoV-2 virus

  Days 201 and 386

Other Outcomes (5)

• Specific cell-mediated immunity (CMI) response induced by the vaccine against the SARS-CoV-2 virus

  Day 21, 201 and 386

• Specific antibody response induced by the vaccine against plant glycans

  Day 21, 201 and 386

• Further characterization of the immune response and the safety profile of the Coronavirus-Like Particle COVID-19 Vaccine

  Day 21, 42, 201, 386

Study Arms (9)

Vaccine (3.75 µg) unadjuvanted

EXPERIMENTAL

• Group 1: 3.75 µg of the Coronavirus-Like Particle COVID-19 Vaccine

Biological: Intramuscular Vaccine

Vaccine (3.75 µg) adjuvanted with CpG 1018

EXPERIMENTAL

• Group 2: 3.75 µg of the Coronavirus-Like Particle COVID-19 Vaccine adjuvanted with CpG 1018

Biological: Intramuscular Vaccine

Vaccine (3.75 µg) adjuvanted with AS03

EXPERIMENTAL

• Group 3: 3.75 µg of the Coronavirus-Like Particle COVID-19 Vaccine adjuvanted with AS03

Biological: Intramuscular Vaccine

Vaccine (7.5 µg) unadjuvanted

EXPERIMENTAL

• Group 4: 7.5 µg of the Coronavirus-Like Particle COVID-19 Vaccine unadjuvanted

Biological: Intramuscular Vaccine

Vaccine (7.5 µg) adjuvanted with CpG 1018

EXPERIMENTAL

• Group 5: 7.5 µg of the Coronavirus-Like Particle COVID-19 Vaccine adjuvanted with CpG 1018

Biological: Intramuscular Vaccine

Vaccine (7.5 µg) adjuvanted with AS03

EXPERIMENTAL

• Group 6: 7.5 µg of the Coronavirus-Like Particle COVID-19 Vaccine adjuvanted with AS03

Biological: Intramuscular Vaccine

Vaccine (15 µg) unadjuvanted

EXPERIMENTAL

• Group 7: 15 µg of the Coronavirus-Like Particle COVID-19 Vaccine unadjuvanted

Biological: Intramuscular Vaccine

Vaccine (15 µg) adjuvanted with CpG 1018

EXPERIMENTAL

• Group 8: 15 µg of the Coronavirus-Like Particle COVID-19 Vaccine adjuvanted with CpG 1018

Biological: Intramuscular Vaccine

Vaccine (15 µg) adjuvanted with AS03

EXPERIMENTAL

• Group 9: 15 µg of the Coronavirus-Like Particle COVID-19 Vaccine adjuvanted with AS03

Biological: Intramuscular Vaccine

Interventions

Intramuscular Vaccine BIOLOGICAL

Subjects will receive two intramuscular (IM) injections 21 days apart (Day 0 and Day 21), into the deltoid region of the alternating arm (each arm will be injected once), with their assigned vaccine.

Vaccine (15 µg) adjuvanted with AS03; Vaccine (15 µg) adjuvanted with CpG 1018; Vaccine (15 µg) unadjuvanted; Vaccine (3.75 µg) adjuvanted with AS03; Vaccine (3.75 µg) adjuvanted with CpG 1018; Vaccine (3.75 µg) unadjuvanted; Vaccine (7.5 µg) adjuvanted with AS03; Vaccine (7.5 µg) adjuvanted with CpG 1018; Vaccine (7.5 µg) unadjuvanted

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must have read, understood, and signed the informed consent form (ICF) prior to participating in the study; subjects must also complete study-related procedures and communicate with the study staff at visits and by phone during the study;
• At the Screening visit (Visit 1), male and female subjects must be 18 to 55 (has not yet had his/her 56th birthday) years of age, inclusive;
• At Screening (Visit 1) and Vaccination (Visit 2), subject must have a body mass index (BMI) of ≥ 18.5 and \< 25 kg/m2;
• Subjects are considered by the Investigator to be reliable and likely to cooperate with the assessment procedures and be available for the duration of the study;
• Female subjects of childbearing potential must have a negative serum pregnancy test result at Screening (Visit 1) and a negative urine pregnancy test result at Vaccination (Visit 2 and Visit 4).
• Non-childbearing females are defined as:
• Surgically-sterile (defined as bilateral tubal ligation, hysterectomy or bilateral oophorectomy performed more than one month prior to the first study vaccination); or
• Post-menopausal (absence of menses for 12 consecutive months and age consistent with natural cessation of ovulation);
• Female subjects of childbearing potential must use an effective method of contraception for one month prior to vaccination (Visit 2) and agree to continue employing highly effective birth control measures for at least one month after the last administration of the investigational product (or in the case of early termination, she must not plan to become pregnant for at least one month after her last study vaccination). The following relationship or methods of contraception are considered to be highly effective:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
• Oral;
• Intravaginal;
• Transdermal;
• Progestogen-only hormonal contraception associated with inhibition of ovulation:
• Oral;

You may not qualify if:

• Subjects who meet any of the following criteria at the Screening (Visit 1) and/or Vaccination (Visit 2) visits will not be eligible for participation in this study; no protocol waivers are allowed. All Investigator assessment-based judgements must be thoroughly documented in the source documents:
• Clinically significant acute or chronic pulmonary (including but not limited to chronic obstructive pulmonary disease or asthma), cardiovascular (including but not limited to arterial hypertension, coronary artery disease, or congestive heart failure), renal, metabolic (including but not limited to type 2 diabetes), or other somatic (medical) or neuropsychiatric illness within 3 months prior to Screening (Visit 1), excessive alcohol use or drug abuse, as determined by medical history, physical examination, vital signs, and clinical laboratory tests.
• Any unexplained clinical syndrome (including, but not limited to, chronic fatigue syndrome, Raynaud's syndrome, unexplained pain syndromes such as fibromyalgia, etc.);
• Acute disease defined as presence of any moderate or severe acute illness with or without a fever within 48 hours prior to Vaccination (Visit 2);
• Prior exposure to SARS-CoV-2 as determined by detection of IgM or IgG antibodies against SARS-CoV-2 at Screening (Visit 1) and Vaccination (Visit 2);
• Administration of any medication or treatment that may alter the vaccine immune responses, such as:
• Systemic glucocorticoids within one month prior to Vaccination (Visit 2). Inhaled, nasal, dermal, intraarticular, ophthalmic and other topical glucocorticoids are permitted;
• Cytotoxic, antineoplastic, or immunosuppressant drugs - within 36 months prior to Vaccination (Visit 2);
• Any immunoglobulin preparations or blood products, blood transfusion - within 6 months prior to Vaccination (Visit 2);
• Administration of any vaccine within 30 days prior to Vaccination (Visit 2); planned administration of any vaccine during the study (up to blood sampling on Day 42 of the study). Immunization on an emergency basis during the study will be evaluated on case-by-case basis by the Investigator;
• Administration of any other SARS-CoV-2 / COVID-19, or other experimental coronavirus vaccine at any time prior to or during the study;
• Known current or previous laboratory-confirmed SARS-CoV-1 or SARS-CoV-2 / COVID 19 infection as documented by a positive PCR test or positive serological test;
• Subjects at high risk of contracting SARS-CoV-2/COVID-19 infection, including but not limited to the individuals with known close contact of anyone with laboratory-confirmed SARS-CoV-2 / COVID-19 infection within 2 weeks prior to vaccine administration, those who traveled outside Canada for any duration within 30 days before the study vaccination, healthcare workers in acute care hospitals, rehabilitation hospitals, mental health hospitals, long term care facilities, emergency departments, and others who through their work must come into close face-to-face contact with their clients or patients (including, but not limited to, physiotherapists, dentists, hair dressers/barbers, etc.);
• Use of any investigational or non-registered product within 30 days or 5 half-lives, whichever is longer, prior to Vaccination (Visit 2) or planned use during the study period;
• Use of any prescription medication on a regular basis for more than 30 continuous days within the last 3 months, with the following exceptions:

Sponsors & Collaborators

• Medicago: lead

Study Sites (2)

Syneos Health

Montreal, Quebec, Canada

Location

Syneos Health

Québec, Quebec, Canada

Location

Related Publications (1)

• Ward BJ, Gobeil P, Seguin A, Atkins J, Boulay I, Charbonneau PY, Couture M, D'Aoust MA, Dhaliwall J, Finkle C, Hager K, Mahmood A, Makarkov A, Cheng MP, Pillet S, Schimke P, St-Martin S, Trepanier S, Landry N. Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19. Nat Med. 2021 Jun;27(6):1071-1078. doi: 10.1038/s41591-021-01370-1. Epub 2021 May 18.

  PMID: 34007070 DERIVED

Study Officials

• Brian J Ward, MD

  Medicago

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 29, 2020
• Study Start: July 10, 2020
• Primary Completion: September 20, 2020
• Study Completion: August 30, 2021
• Last Updated: April 6, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)