South African National Clinical Trials Registry
South African Medical Research Council, Cochrane South Africa
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: sactradmin@mrc.ac.za Website: sanctr.samrc.ac.za
Trial no.: DOH-27-112021-5423 Date of Approval: 15/11/2021
Trial Status: Approved
TRIAL DESCRIPTION
Public title A Phase 1, First-in-Human, Proof-of-Concept, Dose Escalation Study to Assess the Safety, Tolerability and Immunogenicity of an Oral Anti-SARS-CoV-2 Vaccine (PRAK-03202) in Healthy Volunteers
Official scientific title A Phase 1, First-in-Human, Proof-of-Concept, Dose Escalation Study to Assess the Safety, Tolerability and Immunogenicity of an Oral Anti-SARS-CoV-2 Vaccine (PRAK-03202) in Healthy Volunteers
Brief summary describing the background and objectives of the trial The current coronavirus disease 2019 (COVID-19), caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a public health emergency of international concern (PHEIC) by the World Health Organization (WHO) on January 30, 2020. The principal disease manifestations include fever, cough and fatigue, with some patients suffering gastrointestinal distress. Elderly people and individuals with history of heart and kidney diseases are highly susceptible to infection and have significantly succumbed to acute respiratory distress syndrome (ARDS) and cytokine storm. Its pandemic dimensions have triggered a wave of drug and vaccine development research in efforts to curb its spread and reduce morbidity and mortality. Currently, there are several vaccines commercially available, most of which target the viral spike (S) protein expressed on the virus membrane and recognized by the host angiotensin-converting enzyme 2 (ACE-2) receptor.2 However, due to the high mutagenic rate of S, there is concern that uni-antigenic vaccine products may be less effective as the virus continues to evolve and undergo genetic changes. PRAK-03202 is a multi-antigenic virus-like particle (VLP)-based vaccine that targets three key structural SARS-CoV-2 proteins. Simultaneous targeting of several virus proteins is expected to elicit a robust immune response, that will be effective against all virus strains. The primary objective of this study is to assess the safety and tolerability of prophylactic oral PRAK-03202 vaccine in healthy volunteers after two doses.
Type of trial CCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID-19
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 01/10/2021
Actual trial start date 13/12/2021
Anticipated date of last follow up 15/06/2023
Actual Last follow-up date 12/06/2023
Anticipated target sample size (number of participants) 24
Actual target sample size (number of participants) 25
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Single Group Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Vaccine 250 micrograms received twice, 21 days apart. Healthy subjects will be dosed twice to receive an oral dose of the vaccine 21 days apart. Follow-up period will be 24 weeks from first dose. This is an open label, single-center, phase 1, FIH, proof-of-concept, dose escalation, dose-finding study in up to 24 healthy volunteers. The study will evaluate the safety, tolerability, and immunogenicity of two dose concentrations 250micrograms or 500 micrograms PRAK-03202 vaccine administered orally as a two-dose schedule administered 21 days apart. 12
Experimental Group Vaccine 500 micrograms twice 21 days apart Healthy subjects will be dosed twice to receive an oral dose of the vaccine 21 days apart. Follow-up period is 24 weeks from first vaccine dose. This is an open label, single-center, phase 1, FIH, proof-of-concept, dose escalation, dose-finding study in up to 24 healthy volunteers. The study will evaluate the safety, tolerability, and immunogenicity of two dose concentrations 250g or 500g PRAK-03202 vaccine administered orally as a two-dose schedule administered 21 days apart. 12
Control Group NA NA NA NA 0 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Male or female participants between the ages of 18 and 85 years, inclusive, at enrolment. 2. Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures. 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. 4. Capable of giving personal signed informed consent. 5. Females of childbearing potential and males must be willing to use effective methods of contraception from at least 14 days prior to 1st oral vaccination through 90 days after 2nd oral vaccination. Male must agree to use condom or occlusive cap with spermicidal agents as well as to avoid sperm donation from time of first oral vaccination through 90 days after 2nd vaccination Females of childbearing potential must: a. have a negative serum pregnancy test result at Screening. b. agree to avoid becoming pregnant while receiving the Investigational Drug (ID) for at least 14 days prior to ID administration and for 90 days following their last dose of the ID. c. agree to use an acceptable method of contraception at least 14 days prior to the ID administration and for 90 days following their last dose of the ID. Acceptable methods of contraception are hormonal contraception (contraceptive pill or injection) PLUS an additional barrier method of contraception such as a diaphragm, condom, sponge, or spermicide. d. In the absence of hormonal contraception, double-barrier methods must be used which include a combination of any two of the following: diaphragm, condom, copper intrauterine device, sponge, or spermicide, and must be used for at least 14 days prior to administration of the ID and for 90 days following their last dose of the ID. e. Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject’s preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception. f. Females who are not of childbearing potential are defined as: i. Postmenopausal (defined as at least 12 months with no menses in women ≥45 years of age); OR ii. Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; OR iii. Have a congenital or acquired condition that prevents childbearing. Any medical or psychiatric condition (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study. 2. Known infection with human immunodeficiency virus (HIV), hepatitis C virus antibody (HCV Ab), or hepatitis B virus antibody (HBV Ab). 3. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the study intervention(s). 4. Receipt of medications intended to prevent COVID-19. 5. Previous vaccination with any coronavirus vaccine. 6. Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19 7. Positive serological test for SARS-CoV-2 IgM and/or IgG antibodies at the screening visit. 8. SARS-CoV-2 NAAT-positive nasal swab within 48 hours before receipt of study intervention. 9. Individuals currently working in occupations with high risk of exposure to SARS-CoV-2 (e.g., healthcare worker, emergency response personnel). 10. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. 11. Women who are pregnant, planning a pregnancy or breastfeeding. 12. Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, 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. 13. Receipt of blood/ Adult: 19 Year(s)-105 Year(s) 18 Year(s) 85 Year(s) Both
APPROVALS
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 29/09/2021 Pharma Ethics Committee
Ethics Committee Address
Street address City Postal code Country
123 Amkor Road, Lyttelton Manor Ext 3 Centurion 0157 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 28/10/2021 SAHPRA
Ethics Committee Address
Street address City Postal code Country
CSIR Reception Building 38a Meiring Naudé Road Brummeria Pretoria Pretoria 0001 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To assess the safety and tolerability of prophylactic oral PRAK-03202 vaccine in healthy volunteers after two doses. From Day 1 to week 3 after each vaccination where Day 1 is the day of vaccination
Secondary Outcome To describe the immune responses elicited by prophylactic oral PRAK-03202 vaccine as assessed by IgG against VLP titers in healthy volunteers after two doses. Exploratory endpoints: IgG against VLP titters, will be assessed from Week 3 through week 24 and will be evaluated descriptively.
Secondary Outcome To describe the immune responses elicited by prophylactic oral PRAK-03202 vaccine as assessed by IgA against VLP titers in healthy volunteers after two doses. Immunogenicity assessments for SARS-CoV-2 VLP IgA, titers from Week 3 through week 24
Secondary Outcome To describe the cell mediated immune responses elicited by prophylactic oral PRAK-03202 vaccine as assessed by specific T-Cells activation in healthy volunteers after two doses. Assessment of T-Cell activation from week 3 through week 24
Secondary Outcome To describe the immune responses elicited by prophylactic oral PRAK-03202 vaccine as assessed by Anti-SARS-CoV-2 neutralizing titers, Spike1 (S1)-binding IgG titers, Envelope (E)-binding IgG titers, Membrane (M) binding IgG titers in healthy volunteers after two doses. Day 1 through week 24
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Tickerdoc Research Netcare Sunninghill Hospital Cnr. Nanyuki and Witkoppen Road Room 31 2nd Floor West Wing Sunninghill 2191 South Africa
Newtown Clinical Research Centre 104 Rahima Moosa Street First Floor Newgate Centre Newtown Johannesburg 2001 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Oramed Pharmaceuticals Ltd. 20 Mamilla St. Jerusalem 9414904 Israel
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Oramed Pharmaceuticals Ltd. 20 Mamilla St Jerusalem 9414904 Israel Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Eric Quinton Klug drklug@tickerdoc.co.za 0027118061835 Netcare Sunninghill Hospital Cnr. Nanyuki and Witkoppen Road
City Postal code Country Position/Affiliation
Sunninghill 2191 South Africa Principal Investigator
Role Name Email Phone Street address
Public Enquiries Eric Quinton Klug drklug@tickerdoc.co.za 0027118061835 Netcare Sunninghill Hospital Cnr. Nanyuki and Witkoppen Road
City Postal code Country Position/Affiliation
Sunninghill 2191 South Africa Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Miriam Kidron miriam@oramed.com +97225660001 20 Mamilla Street
City Postal code Country Position/Affiliation
Jerusalem 9414904 Israel Chief Scientific Officer and Director
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Oramed will make available data from these trials 12 months after study completion. Patient-level data will be anonymized in accordance with applicable privacy laws and regulations. CSRs will have personally identifiable information redacted. Data requests are considered from qualified researchers with the appropriate competencies to perform the proposed analyses. Oramed fulfills its commitment to publicly disclose clinical study results through posting the results of study on ww.clinicaltrials.gov(ClinicalTrials.gov), and/or https://www.oramed.com. Informed Consent Form,Study Protocol 12 months Data requests are considered from qualified researchers with the appropriate competencies to perform the proposed analyses. Research teams must include a biostatistician. Data will not be provided to applicants with significant conflicts of interest, including individuals requesting access for commercial/competitive or legal purposes.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 26/02/2022 Actual start date completed. 13 Dec 2021
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 31/10/2022 Recruitment slow and anticipated to complete 04 Nov 2022 29 Apr 2022 15 May 2023
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 04/05/2023 Estimated completion date based on last participant last visit 15 May 2023 15 Jun 2023
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 08/12/2023 Updating last participant visit 12 Jun 2023
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 09/01/2023 Update final enrolment 26
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 04/05/2023 Actual final enrolment status. 26 25
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 26/02/2022 Update that study is currently recruiting Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 09/01/2023 Recruitment completed Recruiting Closed to recruitment,follow-up continuing
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 08/12/2023 Study closed. Closed to recruitment,follow-up continuing Completed
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Exclusion criteria 31/10/2022 Exlusion 8 changed to: SARS-CoV-2 NAAT-positive nasal swab within 48 hours before receipt of study intervention. Justification: Timeline of nasal swab results (SARS-CoV-2 NAAT) was prolonged from "within 24 hours" to "within 48 hours" to ensure that results will be obtained on time prior to participant receipt of study vaccine. Any medical or psychiatric condition (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study. 2. Known infection with human immunodeficiency virus (HIV), hepatitis C virus antibody (HCV Ab), or hepatitis B virus antibody (HBV Ab). 3. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the study intervention(s). 4. Receipt of medications intended to prevent COVID-19. 5. Previous vaccination with any coronavirus vaccine. 6. Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19 7. Positive serological test for SARS-CoV-2 IgM and/or IgG antibodies at the screening visit. 8. SARS-CoV-2 NAAT-positive nasal swab within 24 hours before receipt of study intervention. 9. Individuals currently working in occupations with high risk of exposure to SARS-CoV-2 (e.g., healthcare worker, emergency response personnel). 10. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. 11. Women who are pregnant, planning a pregnancy or breastfeeding. 12. Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, 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. 13. Receipt of blood/ Any medical or psychiatric condition (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study. 2. Known infection with human immunodeficiency virus (HIV), hepatitis C virus antibody (HCV Ab), or hepatitis B virus antibody (HBV Ab). 3. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the study intervention(s). 4. Receipt of medications intended to prevent COVID-19. 5. Previous vaccination with any coronavirus vaccine. 6. Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19 7. Positive serological test for SARS-CoV-2 IgM and/or IgG antibodies at the screening visit. 8. SARS-CoV-2 NAAT-positive nasal swab within 48 hours before receipt of study intervention. 9. Individuals currently working in occupations with high risk of exposure to SARS-CoV-2 (e.g., healthcare worker, emergency response personnel). 10. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. 11. Women who are pregnant, planning a pregnancy or breastfeeding. 12. Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, 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. 13. Receipt of blood/
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 31/10/2022 Secondary Objectives were deleted. Justification: Secondary objectives were updated and were defined as part of the exploratory objectives. To describe the immune responses elicited by prophylactic oral PRAK-03202 vaccine as assessed by IgG against VLP titers in healthy volunteers after two doses. Justification: o present the laboratory measurements that may identify SARS CoV2 by the measurements of (as measured by the developed laboratory kit): • IgG against VLP titers • IgA against VLP titers • Specific T-Cells activation Secondary Outcome, To describe the immune responses elicited by prophylactic oral PRAK-03202 vaccine as assessed by IgG titers in healthy volunteers after two doses., Immunogenicity assessments for SARS-CoV-2 IgG, titers from Week 3 through week 24 Secondary Outcome, To describe the immune responses elicited by prophylactic oral PRAK-03202 vaccine as assessed by IgG against VLP titers in healthy volunteers after two doses., Exploratory endpoints: IgG against VLP titters, will be assessed from Week 3 through week 24 and will be evaluated descriptively.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 31/10/2022 Justification: To present the laboratory measurements that may identify SARS CoV2 by the measurements of (as measured by the developed laboratory kit): • IgG against VLP titers • IgA against VLP titers • Specific T-Cells activation Secondary Outcome, To describe the immune responses elicited by prophylactic oral PRAK-03202 vaccine as assessed by IgA titers in healthy volunteers after two doses., Immunogenicity assessments for SARS-CoV-2 IgA, titers from Week 3 through week 24 Secondary Outcome, To describe the immune responses elicited by prophylactic oral PRAK-03202 vaccine as assessed by IgA against VLP titers in healthy volunteers after two doses. , Immunogenicity assessments for SARS-CoV-2 VLP IgA, titers from Week 3 through week 24
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 31/10/2022 Justification: To present the laboratory measurements that may identify SARS CoV2 by the measurements of (as measured by the developed laboratory kit): • IgG against VLP titers • IgA against VLP titers • Specific T-Cells activation Secondary Outcome, To describe the immune responses elicited by prophylactic oral PRAK-03202 vaccine as assessed by IgM titers in healthy volunteers after two doses., Immunogenicity assessments for SARS-CoV-2 IgM titers from week 3 through week 24 Secondary Outcome, To describe the cell mediated immune responses elicited by prophylactic oral PRAK-03202 vaccine as assessed by specific T-Cells activation in healthy volunteers after two doses., Assessment of T-Cell activation from week 3 through week 24
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 31/10/2022 Justification: Due to the development of additional laboratory kits that may identify Anti-SARS-CoV-2 neutralizing titers and specific IgG titers. Secondary Outcome, To describe the immune responses elicited by prophylactic oral PRAK-03202 vaccine as assessed by Anti-SARS-CoV-2 neutralizing titers, Spike1 (S1)-binding IgG titers, Envelope (E)-binding IgG titers, Membrane (M) binding IgG titers in healthy volunteers after two doses., Day 1 through week 24
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 31/10/2022 Additional site included in the study to enhance recruitment rate. Newtown Clinical Research Centre, 104 Rahima Moosa Street First Floor Newgate Centre Newtown, Johannesburg, 2001, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Trial Information COMPLETION_STATUS 08/12/2023 Study completed. Close-out visit completed 23 Nov 2023. In Progress Completed