Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202108781239363 Date of Approval: 17/08/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A study to assess a new Lassa Virus Vaccine in healthy volunteers
Official scientific title A Phase 1 Randomized, Blinded, Placebo Controlled, Dose-Escalation and Dosing Regimen Selection Study to Evaluate the Safety and Immunogenicity of rVSV-Vectored Lassa Virus Vaccine in Healthy Adults at Multiple Sites in West Africa
Brief summary describing the background and objectives of the trial Lassa fever is an acute viral illness caused by a zoonotic single-stranded enveloped ribonucleic acid (RNA) virus predominant in West Africa.The main reservoir for LASV is the multimammate rat. Infected rats are asymptomatic and shed the virus in their urine and droppings. Transmission to humans is typically via inhalation or ingestion of infected rodent urine, saliva, or droppings that are in or near food sources, or by direct contact with an infected rat. Human-to-human transmission of LASV is through contact with blood, urine, or faeces from an infected individual, or contact with contaminated objects. The clinical and laboratory diagnosis of Lassa fever is difficult because the symptoms are non-specific in the early stages of the disease resembling severe malaria, typhoid fever, and other hemorrhagic fevers. The disease has a gradual onset with prodrome of fever, malaise, and general weakness, which is immediately followed by headache, sore throat, muscle pain, chest pain, nausea, vomiting, diarrhea, cough, and abdominal pain. Severe cases may result in facial swelling, pulmonary oedema, bleeding (in mouth, eyes, nose, vagina), and shock. Neurological problems have been described, including transient and permanent hearing loss (~25% of subjects), tremors, and encephalitis. There is currently no approved therapeutic treatment or prophylactic vaccine for the prevention of LASV infection or Lassa fever. This study is therefore a First-in-Human study to evaluate the safety and immunogenicity of EBS-LASV vaccine for the prevention of Lassa Fever. The primary efficacy objective is to evaluate the humoral immune response to EBS-LASV vaccine at various dose levels and dosing schedules for the purpose of selecting two regimens (dose and schedule) for further evaluation in a Phase 2 study. The primary safety objective is to evaluate the safety and tolerability of increasing dose levels of EBS-LASV vaccine administered as a single dose or two-dose series.
Type of trial RCT
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 Lassa Fever
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 31/03/2022
Actual trial start date 22/08/2022
Anticipated date of last follow up 30/09/2023
Actual Last follow-up date 03/05/2024
Anticipated target sample size (number of participants) 108
Actual target sample size (number of participants) 36
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
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Simple randomization using a randomization table created by a computer software program Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group rVSVn4g LASVgpc1 EBS LASV Part A Cohort 1/Arm 1.1 EBS-LASV 1×10e5 TCID50 (Low) dose on Day 1 and Day 29 Cohort 2/Arm 2.1 EBS-LASV 1×10e6 TCID50 (Medium) dose on Day 1 and Day 29 Cohort 3/Arm 3.1 EBS-LASV 1×10e7 TCID50 (High) dose on Day 1 and Day 29 Part B* (Cohort 4) Arm 4.1 EBS-LASV TBD-1 dose on Day 1 and Day 15 (placebo on Days 29, 57) Arm 4.2 EBS-LASV TBD-1 dose on Day 1 and Day 29 (placebo on Days 15, 57) Arm 4.3 EBS-LASV TBD-1 dose on Day 1 and Day 57 (placebo on Days 15, 29) Arm 4.4 EBS-LASV TBD-1 dose on Day 1 only (placebo on Days 29, 15, 57) Arm 4.5 EBS-LASV TBD-2 dose on Day 1 and Day 15 (placebo on Days 29, 57) Arm 4.6 EBS-LASV TBD-2 dose on Day 1 and Day 29 (placebo on Days 15, 57) Arm 4.7 EBS-LASV TBD-2 dose on Day 1 and Day 57 (placebo on Days 15, 29) *Safety and immunogenicity results from Part A (dose escalation) will inform on the to be determined (TBD) dose selection (further assess two doses from the low, medium, or high) for Part B (dose and dosing regimen assessment) Part A two equivalent dose series on Days 1 and 29 with follow-up throughout the study and up to Day 197 end of study. Part B dosing on Day 1 as a single dose or two equivalent dose series with follow-up throughout the study and up to Day 225 end of study. To maintain the double blind, all Part B enrolled subjects to receive vaccinations (EBS-LASV and/or placebo) on Days 1, 15, 29, and 57 Each vaccination will be a 0.5 mL intramuscular injection to be administered into the deltoid muscle 90
Control Group Diluent Part A/Arms 1.2. 2.2, and 3.2 dosed on Day 1 and Day 29 Part B/Arm 4.8 doses on Days 1, 15, 29, and 57 Part A dosing on Days 1 and 29 with follow-up throughout the study and up to Day 197 end of study. Part B dosing on Days 1, 15, 29, and 57 with follow-up throughout the study and up to Day 225 end of study. Each vaccination will be a 0.5 mL intramuscular injection to be administered into the deltoid muscle 18 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Subject understands the study as outlined in the informed consent form (ICF) and its procedures, agrees to study-related assessments, study visits, and voluntarily provides informed consent by signing the ICF. 2. Age: 18 to 50 years (inclusively). 3. Body mass index (BMI) of 18 to 30 kg/m2 at Screening Visit. 4. Hearing threshold between -10 to 15 decibels (dB) across low, middle, and high frequencies as measured by audiometry. 5. Generally healthy, in the opinion of the Investigator, based on medical history, physical examination and screening laboratory assessments. 6. Women who are EITHER: i. Not of childbearing potential (CBP): anatomically sterile, or post-menopausal (defined as elevated FSH and ≥12 months without menses). OR: ii. Meet all the below criteria: • Negative serum pregnancy test at Screening Visit. • Negative urine pregnancy test immediately prior to dosing at Day 1. • Do not intend to become pregnant during the study. • Using one of these medically acceptable methods of contraception (if woman of CBP) for the duration of participation, such as: • Hormonal contraceptives (e.g., implants, pills, patches [combined estrogen and progestogen, or progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine hormone-releasing system]) initiated ≥30 days prior to dosing. • Intrauterine device (IUD) inserted ≥30 days prior to dosing. • Bilateral tubal ligation. 1. Currently pregnant or lactating. 2. Laboratory evidence of infection with human immunodeficiency virus (HIV), hepatitis B or C viruses (HBV or HCV). 3. History of cardiac disease. 4. History of severe allergic reaction or anaphylaxis. 5. History of any immunodeficiency or immunocompromising condition that could impact response to IP administration. 6. Receipt or anticipated receipt of blood products from 180 days prior to screening to 30 days post IP administration. 7. Current or past participation in a study with an IP from 30 days prior to screening through study duration. 8. Receipt or anticipated receipt of any vaccines or systemic immunomodulatory agents from 30 days prior to screening to 90 days post IP administration. 9. Evidence of current or past (over the past 5 years) use or treatment for alcohol or drug abuse. 10. Planned medical procedure during the study. 11. Medical condition that, in the opinion of the Investigator, could adversely impact the subject. 12. Chronic or acute severe neurologic condition 13. Clinically significant medical condition or laboratory assessment. 14. Abnormal clinically significant electrocardiogram (ECG) at screening. 15. Acute condition not resolved at least 14 days prior to IP dosing. 16. History of LASV infection/disease. 17. Prior residence greater than 30 days in a LASV-endemic region. 18. Prior receipt of any investigational LASV vaccine. 19. Prior receipt of a VSV-vectored Ebola virus vaccine. 20. Prior known infection with VSV. 21. History of hearing loss. Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 50 Year(s) Both
ETHICS APPROVAL
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 16/03/2022 Navrongo Health Research Centre Institutional Review Board
Ethics Committee Address
Street address City Postal code Country
P. 0. Box 114 Navrongo 114 Ghana
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 30/11/2021 Kintampo Health Research Centre Institutional Ethics Committee
Ethics Committee Address
Street address City Postal code Country
P. O. Box 200 Kintampo Bono East Region 200 Ghana
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 29/03/2022 Ghana Health Service Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
PO Box MB 190 Accra GA-050-33 Ghana
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 29/03/2022 Ghana Health Service Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
PO Box MB 190 Accra GA-050-33 Ghana
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 25/04/2022 Ghana Food and Drugs Authority
Ethics Committee Address
Street address City Postal code Country
P.O. Box CT 2783 Accra CT 2783 Ghana
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 25/04/2022 Ghana Food and Drugs Authority
Ethics Committee Address
Street address City Postal code Country
P.O. Box CT 2783 Ghana CT 2783 Ghana
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Incidence of AEs AEs will be collected 28-days following each vaccination
Primary Outcome Incidence of serious adverse events /SAEs SAEs will be collected throughout the entire study duration
Secondary Outcome LASV neutralizing antibody /nAb/ levels Two to Four weeks after the last EBS-LASV vaccination
Secondary Outcome LASV-GP-specific immunoglobulin G /IgG/ levels Two to Four weeks after the last EBS-LASV vaccination
Primary Outcome Incidence of adverse event of special interest /AESI/ AESI will be collected throughout the entire study duration
Primary Outcome Incidence of rVSV viral shedding in blood, urine, and saliva Measured periodically and up to 4 weeks post-last vaccination /and possibly beyond
Primary Outcome Incidence of reactogenicity events /solicited systemic and injection site reactions Reactogenicities will be collected seven days following each vaccination
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kintampo Health Research Centre P. O. Box 200 Kintampo Bono East Region Ghana
Navrongo Health Research Centre P. O. Box 114 Navrongo Upper East Region Ghana
FUNDING SOURCES
Name of source Street address City Postal code Country
Emergent Product Development Gaithersburg Inc 400 Professional Drive Gaithersburg Maryland 20879 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Emergent Product Development Gaithersburg Inc 400 Professional Drive Gaithersburg Maryland 20879 United States of America Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Quintiles West Africa Ltd 19 Kofi Annan Accra Ghana
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Seyram Kaali kaali.seyram@kintampo-hrc.org +233546381925 P. O. Box 200
City Postal code Country Position/Affiliation
Kintampo Ghana Site Principal Investigator
Role Name Email Phone Street address
Principal Investigator Patrick Ansah lonpoa2@gmail.com +233245279984 P. O. Box 114
City Postal code Country Position/Affiliation
Navrongo Ghana Site Principal Investigator
Role Name Email Phone Street address
Public Enquiries Hugo Astacio hastacio@ebsi.com +2042754441 155 Innovation Drive
City Postal code Country Position/Affiliation
Winnipeg R3T 5Y3 Canada Snr Manager Product Safety Physicia
Role Name Email Phone Street address
Scientific Enquiries Hugo Astacio hastacio@ebsi.com +2042754441 155 Innovation Drive
City Postal code Country Position/Affiliation
Winnipeg R3T 5Y3 Canada Snr Manager Product Safety Physician
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The Sponsor, PI, the SMC, the IEC/IRBs and the regulatory authorities, as appropriate. A primary manuscript describing safety and immune responses in this trial will be prepared promptly after the data analysis is available. Authors will be representatives of each trial site, the data management and statistical analysis center, the laboratories and CEPI, subject to the generally accepted criteria of contributions to the design and conduct of the study, the analysis of data and writing of the manuscript. Manuscripts will be reviewed by representatives of each participating group as specified in the Clinical Trial Agreements. Informed Consent Form,Statistical Analysis Plan,Study Protocol The trial completion date will be recorded on this website as the date of database lock. The clinical study report is anticipated to be completed within 6 months after database lock. Clinical data will be made publicly available, without personal identifiers, according to donor requirements..
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