Lassa Fever
Conditions
Brief summary
A Phase 2 Randomized, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of rVSV∆G-LASV-GPC Vaccine in Adults and Children Residing in West Africa
Detailed description
rVSVΔG-LASV-GPC is a candidate vaccine that has been shown to be safe and protects against LF disease in animals. The vaccine was studied studied in a Phase 1 trial and has been well tolerated and immunogenic. This Phase 2 trial will add to data from the Phase 1 trial to establish a broader profile of safety and immunogenicity in adults and expand the population to include a subset of adults with HIV infection as well as older adults and healthy children, in preparation for an efficacy trial in West Africa. Primary Objective: • To evaluate the safety and tolerability of rVSVΔG-LASV-GPC vaccine at 2 different dosage levels in adults, including PLWH, and in children Secondary Objectives: • To determine binding LASV-GPC-specific antibody responses induced by rVSVΔG-LASV-GPC vaccine • To determine neutralizing LASV-GPC-specific antibody responses induced by rVSVΔG-LASV-GPC vaccine in a subset of participants in each group • To evaluate the magnitude and duration of the rVSVΔG-LASV-GPC vaccine viremia in plasma in a subset of participants. • To evaluate the magnitude and duration of the rVSVΔG-LASV-GPC vaccine shedding in saliva and urine, and possibly semen and cervicovaginal fluid, in a subset of participants Exploratory Objective • To explore the characteristics of the immune responses induced by rVSVΔG-LASV-GPC vaccine in a subset of participants
Interventions
DRUGDay 1 Lower Dose (2×106 pfu)
rVSV∆G-LASV-GPC
DRUGDay 1 Higher Dose (1×107 pfu)
rVSV∆G-LASV-GPC
DRUGPlacebo
Placebo
Sponsors
Coalition for Epidemic Preparedness Innovations
International AIDS Vaccine Initiative
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Study staff and participants will be blinded in terms of active product versus placebo.
Eligibility
Sex/Gender
ALL
Age
18 Months to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Adults, adolescents, and children in good general health as assessed by medical history and physical examination (group-specific criteria apply). * At least 18 months old on the day of screening and not more than 70 years old on the day of vaccination (group-specific criteria apply). * Participant or parent/guardian willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study. * In the opinion of the Principal Investigator (PI) or designee and based on Assessment of Informed Consent Understanding (AOU), participant or parent/guardian has understood the information provided and potential impact and/or risks linked to administration and participation in the trial; written informed consent will be obtained before any study-related procedures are performed. Children old enough to understand the procedures will be asked to assent, in addition to parent/guardian consent, in accordance with local requirements. * Willing to undergo HIV testing, risk reduction counselling, and receive HIV test results (group-specific timepoints apply). * All participants of child-bearing potential engaging in sexual activity that could lead to pregnancy must commit to use an effective hormonal contraception or intrauterine device beginning 2 weeks prior and extending for 4 months following receipt of vaccine/placebo. Study sites will choose which methods are most appropriate for their population and this will be specified in the Informed Consent Document (ICD). * All sexually active participants must consistently use male or female condoms with all sexual partners for 4 months following IP administration. * All participants who are not engaging in sexual activity that could lead to pregnancy at screening must agree to utilize an effective method of contraception if they begin engaging in sexual activity that could lead to pregnancy, as outlined above. * All participants of childbearing potential must be willing to undergo a pregnancy test at time points indicated in the SOA. * Willing to forgo donation of blood or any other tissues for transfusion or transplantation, from screening onward throughout the course of the study. Additional Inclusion Criteria For HIV-Infected Participants * Adults who are HIV-infected must meet the following additional inclusion criteria: * Participant must be aged at least 18 years old on the day of screening and not more than 50 years old on the day of vaccination. * Participant must have documented HIV-1 or HIV-2 infection for at least 6 months prior to screening. * Participant must be on a stable (at least 6 months) regimen of Highly Active Antiretroviral Therapy (HAART), as defined as potent anti-HIV treatment including a combination of antiretroviral agents (pre- or post-exposure prophylaxis does not count as HAART). * Participant entering the study should have a screening viral load \<50 copies/ml. * Participant must be willing to continue their HAART and HIV care follow up throughout the study as directed by their regular caregiver and be willing to give access to records of their ongoing care. * Participant must be in an otherwise reasonably good medical condition (absence of acquired immunodeficiency syndrome \[AIDS\]-defining illnesses or clinically significant disease), diagnosed based on physical examination, medical history, and the investigator's clinical judgment. Additional Inclusion Criteria for Pediatric Participants * Each potential pediatric study participant must meet all of the following additional criteria to be enrolled in the study: * Parent(s)/legal guardian must have signed an ICD indicating that they understand the purpose and procedures required for the study, are willing/able to adhere to the study requirements and are willing for their child to participate in the study. Assent must be obtained from adolescents and children in accordance with local regulations and practice. Parent(s)/legal guardian must pass the AOU. * Participant's age on the day of vaccination is within one of the 3 age strata in the study: 12-17 years, 6-11 years, or 18 months -5 years. * Participant must be healthy in the investigator's clinical judgment (and the parent(s)/legal guardian's judgment) based on medical history, physical examination and vital signs performed at screening. * A female adolescent who is of childbearing potential must comply with requirements for contraception. * Adolescents who are sexually active must comply with requirement for use of condoms for 4 months after vaccination. * Participant has received all routine immunizations appropriate for their age as reported by the parent(s)/legal guardian, according to local routine vaccination schedules. Participants are allowed to catch up on routine immunizations if needed or as part of national immunization campaigns. However,
Exclusion criteria
#9 will apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the safety and tolerability of rVSV∆G-LASV-GPC vaccine at 2 different dosage levels in adults, including PLWH, and in children | 14 days | Proportion of participants with Grade 3 or higher reactogenicity, ie, solicited AEs, within 14 days after IP administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To determine binding LASV-GPC-specific antibody responses induced by rVSV∆G-LASV-GPC vaccine | 6 months/2.5 years | Proportion of participants with binding antibody responses to LASV-GPC |
| To determine neutralizing LASV-GPC-specific antibody responses induced by rVSV∆G-LASV-GPC vaccine in a subset of participants in each group | 6 months/2.5 years | Proportion of participants with neutralizing antibody responses against LASV |
| To evaluate the magnitude and duration of the rVSV∆G-LASV-GPC vaccine viremia in plasma in a subset of participants | 6 months/2.5 years | Magnitude and duration of rVSV∆G-LASV-GPC vaccine viremia by culture |
| To evaluate the magnitude and duration of the rVSV∆G-LASV-GPC vaccine shedding in saliva and urine, and possibly semen and cervicovaginal fluid, in a subset of participants | 6 months/2.5 years | Magnitude and duration of rVSV∆G-LASV-GPC vaccine shedding in semen and cervicovaginal secretions by culture |
Countries
Ghana, Liberia, Nigeria
Contacts
Primary ContactGaudensia Mutua
Backup ContactBabalwa Jongihlati
Outcome results
None listed