Phase I vaccine study of pEVAC-PS coronavirus vaccine
| ISRCTN | ISRCTN87813400 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN87813400 |
| EudraCT/CTIS number | 2021-002227-38 |
| IRAS number | 304756 |
| Secondary identifying numbers | IRAS 304756, CPMS 50779 |
- Submission date
- 23/11/2021
- Registration date
- 29/11/2021
- Last edited
- 12/09/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
There is currently no licensed vaccine that can protect across a whole range of the family of Coronaviruses that affect humans (known as Sarbeco Coronaviruses), such as SARS-CoV-2 which causes COVID-19, and SARS. Whilst highly effective vaccines have been produced for COVID-19, variants of the virus have evolved which are somewhat able to evade the immune responses given by vaccination or by previous infection. It is therefore important to develop a vaccine with a very broad range of coverage across the SARS-CoV-2 virus that causes COVID-19, and all its relatives. A vaccine that protects against other Sarbeco coronaviruses will also be useful to provide protection against future potential pandemic viruses.
The purpose of this study is to evaluate a new vaccine designed to protect against all Sarbeco Coronaviruses (and has the potential to protect against the variants of SARS-CoV-2) called pEVAC_PS, at different doses to assess its safety and immune response in healthy volunteers. This is the first study to use the pEVAC_PS vaccine in human participants. It is planned that up to a total of 36 volunteers will participate in the study.
Who can participate?
Healthy adults aged 18 to 50 years, immunised no less than 12 weeks prior with 2 doses of SARS-CoV-2 vaccine, and no evidence of prior SARS-CoV-2 infection.
What does the study involve?
Participants will come to their research site for up to 11 scheduled visits. They will also have a follow-up telephone call 1 day after your first dose of vaccine. All volunteers will attend a screening visit and if you are eligible, will receive two doses of the study vaccine, one month apart. The rest of the visits will be follow-up visits. These visits will be spread across 6 months, but up to 12 months if the dose of vaccine administered is found to be highly effective. Participants will be asked to complete a diary, recording any symptoms you experience after the vaccination for one month following each injection. The first 6 volunteers will take part in Group 1. Further volunteers will be enrolled in subsequent groups depending on the results of the immune responses of participants in Group 1.
What are the possible benefits and risks of participating?
Benefits:
Information gained from the study might help to develop a vaccine for use in preventing infections from Sarbeco Coronaviruses including variants of the SARS-CoV-2 virus which causes COVID-19.
There are no known benefits to participants from taking part in this study.
Risks:
Some procedures in the study may cause discomfort or symptoms.
Vaccine Associated Risks: pEVAC_PS has not previously been studied in human participants and the potential side effects of the vaccine are currently unknown. Most symptoms are expected to be mild, although some effects may also be moderate or severe.
It is important to remember that this vaccine is in the early stages of development and the amount of safety data available is limited, which is part of the reason this study is being conducted.
Where is the study run from?
The study is run from and sponsored by the University Hospital Southampton NHS Foundation Trust, from the NIHR Southampton Clinical Research Facility (UK). There is an additional site at the NIHR Cambridge Clinical Research Facility.
When is the study starting and how long is it expected to run for?
May 2020 to September 2024
Who is funding the study?
UK Research and Innovation.
Who is the main contact?
Professor Saul Faust, s.faust@soton.ac.uk
Contact information
Scientific
NIHR Southampton Clinical Research Facility
University Hospital Southampton NHS Foundation Trust
Southampton
SO16 6YD
United Kingdom
 ORCID ID |
0000-0003-3410-7642 |
|---|---|
| Phone | +44 23 8120 4989 |
| s.faust@soton.ac.uk |
Study information
| Study design | Open label single-centre first-in-human adaptive dose escalation phase I trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | A phase I safety, immunogenicity and dose escalation study of the candidate pan-Sarbeco Coronavirus vaccine pEVAC-PS in SARS-CoV-2 immunised UK healthy adult volunteers |
| Study hypothesis | A vaccine containing DNA coding for a pan-Sarbeco Coronavirus antigen designed using Digital Immune Optimised Synthetic Vaccine (DIOSynVax) technology is safe and tolerable and provides immunity across the range of Sarbeco Coronaviruses, including SARS-CoV and SARS-CoV-2 |
| Ethics approval(s) |
Approved 29/09/2021, South Central - Berkshire Research Ethics Committee (Bristol REC Centre, Temple Quay House, 2 The Square, Temple Quay, Bristol, BS1 6PN, United Kingdom; +44 207 104 8121; berkshire.rec@hra.nhs.uk), ref: 21/SC/0337 |
| Condition | Prevention of COVID-19 and other severe beta-coronavirus infections |
| Intervention | Current interventions as of 24/07/2023: Investigational product: pEVAC-PS Doses: 1.2mg Intradermal (ID), 0.8mg ID, 0.4mg ID, 0.2mg ID Total: 36 volunteers Group 1: 9 volunteers; 2 doses of pEVAC-PS at 0.2mg intradermally Group 2: 9 volunteers; 2 doses of pEVAC-PS at 0.4mg intradermally Group 3: 9 volunteers; 2 doses of pEVAC-PS at 0.8mg intradermally Group 4: 9 volunteers; 2 doses of pEVAC-PS at 1.2mg intradermally Previous interventions: Investigational product: pEVAC-PS Doses: 1.2mg Intradermal (ID), 0.8mg ID, 0.4mg ID, 0.2mg ID Total: 36 volunteers Stage 1 Group 1: 6 volunteers; 2 doses of pEVAC-PS at 0.2mg (lowest dose) intradermally Stage 2 subject to safety and immunogenicity analysis from stage 1 after 4 weeks post 2nd dose - Primary immunogenicity target met Expanded group 1: 12 volunteers; 2 doses of pEVAC-PS at 0.2mg intradermally Review for plan of reduced dose formulation and testing if continued safety and immunogenicity targets met in expanded group - Primary immunogenicity target not met Group 2a: 9 volunteers; 2 doses of pEVAC-PS at 0.4mg intradermally PLUS Group 2b: 9 volunteers; 2 doses of pEVAC-PS at 0.8mg intradermally - Very Poor/No response Group 2a: 9 volunteers; 2 doses of pEVAC-PS at 0.8mg intradermally PLUS Group 2b: 9 volunteers; 2 doses of pEVAC-PS at 1.2mg intradermally Stage 3 subject to safety and immunogenicity analysis from stage 2 after 4 weeks post 2nd dose - Primary immunogenicity target met Group 3: 12 volunteers, 2 doses of pEVAC-PS at the dose with the best immunogenicity and reactogenicity profile from Groups 2a or 2b - Primary immunogenicity target not met at 2x 0.8mg ID Group 2c: 12 volunteers; 2 doses of pEVAC-PS at 1.2mg intradermally |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | pEVAC-PS |
| Primary outcome measure | Safety and reactogenicity measured as: 1. Solicited local reactogenicity signs and symptoms for 7 days following vaccination measured using participant symptom diary entries 2. Solicited systemic reactogenicity signs and symptoms for 7 days following vaccination measured using participant symptom diary entries 3. Unsolicited adverse events (AEs) for 28 days following vaccination measured using participant symptom diary entries 4. Safety laboratory measures measured using routine Haematology and Biochemistry at day 0, 3, 7 and 42 5. Occurrence of disease enhancement episodes measured using surveillance for COVID-19 hospitalisations during the whole study period |
| Secondary outcome measures | 1. Humoral immunogenicity of pEVAC-PS through the analysis of SARS-CoV and SARS-CoV-2 RBD antibody titres at 28 days (4 weeks) after 2 doses of pEVAC-PS have been administered 28 days apart, measured as serology: receptor binding domain (RBD) responses in the majority of vaccinees per group for SARS-CoV and SARS-CoV-2 2. Dose tolerability at 28 days (4 weeks) after the second dose of vaccine measured using participant symptom diary entries 3. Results of immunogenicity at 28 days (4 weeks) after the second dose of vaccine measured using ELISpot 3. Long term (up to 12 months) humoral immunogenicity measured as serology: receptor binding domain (RBD) for SARS-CoV and SARS- CoV-2 RBD pre and post- immunisation. |
| Overall study start date | 21/05/2020 |
| Overall study end date | 01/09/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 50 Years |
| Sex | Both |
| Target number of participants | 36 |
| Total final enrolment | 39 |
| Participant inclusion criteria | Current participant inclusion criteria as of 24/07/2023: 1. Healthy males and non-pregnant females 2. Aged 18 - 50 years 3. Immunised no less than 12 weeks prior with 2 or 3 doses of SARS-CoV-2 vaccine 4. No history of SARS-CoV-2 infection within the past 180 days Previous participant inclusion criteria: 1. Healthy males and non-pregnant females 2. Aged 18 - 50 years 3. Immunised no less than 12 weeks prior with 2 doses of SARS-CoV-2 vaccine 4. No history of serological evidence of prior SARS-CoV-2 infection (seronegative for N) |
| Participant exclusion criteria | Current participant exclusion criteria as of 24/07/2023: 1. History of laboratory-confirmed MERS, SARS-CoV-1 or SARS-CoV-2 infection 2. Have an anti-SARS-CoV-2 and a SARS-CoV-1 RBD response of less than 0.5 or more than 2 AUC (Area Under the Curve) units 3. Planned receipt of any vaccine other than the study intervention within 30 days before and after each study vaccination 4. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate 5. Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting <14 days) 6. Any autoimmune conditions, except mild psoriasis, well-controlled autoimmune thyroid disease, vitiligo or stable coeliac disease not requiring immunosuppressive or immunomodulatory therapy 7. History of allergic disease or reactions likely to be exacerbated by any component of the pEVAC-PS vaccine 8. Any history of angioedema 9. Any history of anaphylaxis 10. Pregnancy, lactation or willingness/intention to become pregnant for 3 months following the last personal dose of vaccine in this trial Previous participant exclusion criteria: 1. History of laboratory-confirmed MERS, SARS-CoV-1 or SARS-CoV-2 infection 2. Seropositive for SARS-CoV-2 Nucleocapsid IgG at screening 3. Have an anti-SARS-CoV-2 and a SARS-CoV-1 RBD response of more than 2 AUC (Area Under the Curve) units 4. Planned receipt of any vaccine other than the study intervention within 30 days before and after each study vaccination. 5. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. 6. Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting <14 days). 7. Any autoimmune conditions, except mild psoriasis, well-controlled autoimmune thyroid disease, vitiligo or stable coeliac disease not requiring immunosuppressive or immunomodulatory therapy. 8. History of allergic disease or reactions likely to be exacerbated by any component of the pEVAC-PS vaccine 9. Any history of angioedema. 10. Any history of anaphylaxis. 11. Pregnancy, lactation or willingness/intention to become pregnant for 3 months following the last personal dose of vaccine in this trial. |
| Recruitment start date | 14/12/2021 |
| Recruitment end date | 01/09/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Southampton
SO16 6YD
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
Hospital/treatment centre
Tremona Road
Southampton
SO16 6YD
England
United Kingdom
| Phone | +44(0)23-8120 5146 |
|---|---|
| sharon.davies-dear@uhs.nhs.uk | |
| Website | https://www.uhs.nhs.uk/ |
"ROR" |
https://ror.org/0485axj58 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- UKRI
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.0 | 17/09/2021 | 24/11/2021 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
12/09/2023: Total final enrolment added.
24/07/2023: The following changes were made:
1. The overall study end date has been changed from 01/05/2023 to 01/09/2024.
2. The interventions were changed.
3. The participant inclusion criteria were changed.
4. The participant exclusion criteria were changed.
5. The recruitment end date was changed from 01/05/2022 to 01/09/2023.
6. The participating study centre NIHR Cambridge Clinical Research Facility was added.
7. The plain English summary was updated accordingly.
8. The intention to publish date was changed from 01/05/2024 to 01/12/2025.
07/12/2021: Internal review.
24/11/2021: Trial's existence confirmed by South Central - Berkshire Research Ethics Committee.
