A Phase 1, Randomized, First-in-human, Open-label Study to Evaluate the Safety and Immunogenicity of eOD-GT8 60mer mRNA Vaccine (mRNA-1644) and Core-g28v2 60mer mRNA Vaccine (mRNA-1644v2-Core) in HIV-1 Uninfected Adults in Good General Health
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Hiv
- Sponsor
- International AIDS Vaccine Initiative
- Enrollment
- 56
- Locations
- 4
- Primary Endpoint
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
- Status
- Active, Not Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
A Phase 1, Randomized, First-in-human, Open-label Study to Evaluate the Safety and Immunogenicity of eOD-GT8 60mer mRNA Vaccine (mRNA-1644) and Core-g28v2 60mer mRNA Vaccine (mRNA-1644v2-Core) in HIV-1 Uninfected Adults in Good General Health
Detailed Description
A Phase 1, Randomized, First-in-human, Open-label Study to Evaluate the Safety and Immunogenicity of eOD-GT8 60mer mRNA Vaccine (mRNA-1644) and Core-g28v2 60mer mRNA Vaccine (mRNA-1644v2-Core) in HIV-1 Uninfected Adults in Good General Health. The hypothesis is that sequential vaccination by a germline-targeting prime followed by directional boost immunogens can induce specific classes of B-cell responses and guide their early maturation toward broadly neutralizing antibody (bnAb) development through an mRNA platform. Fifty-six participants. Adults 18 to 50 years of age who meet all protocol inclusion criteria, who do not meet any protocol exclusion criteria, who understand the study (as demonstrated by the Assessment of \[Informed Consent\] Understanding \[AOU\]), and who can provide written informed consent. Randomization allocation is 16:16:16:8 for Groups 1-4 respectively. There is no blinding in this study. Site and study staff will not be blinded to the IP.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy adults as assessed by a medical history, physical examination, and laboratory tests who are at least 18 years at the time of screening and less than 51 years at the time of first IP administration;
- •Willing to comply with the requirements of the protocol and be 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) results, has understood the information provided and potential impact and/or risks linked to IP administration and participation in the study; written informed consent will be obtained from the participant before any study-related procedures are performed;
- •Willing to undergo HIV testing, risk reduction counseling, and receive HIV test results;
- •All women of reproductive potential who are engaging in sexual activity that could lead to pregnancy must commit to use an effective method of contraception for at least 2 weeks prior to the first IP administration and continue until 4 months following the last IP administration. Effective contraception includes:
- •Condoms (male or female) with or without spermicide
- •Diaphragm or cervical cap with spermicide
- •Intrauterine device
- •Hormonal contraception, including contraceptive implant or injectable
- •Oral contraception
Exclusion Criteria
- •Positive test for HIV-1 or HIV-2;
- •Any clinically relevant abnormality on history or examination, including history of immunodeficiency or autoimmune disease; use of systemic corticosteroids (the use of topical or inhaled steroids is permitted), immunosuppressive, anticancer, antituberculosis, or other medications considered significant by the Investigator within the previous 6 months; Note: The following exceptions are permitted and will not exclude study participation: use of corticosteroid nasal spray for rhinitis, topical corticosteroids for an acute uncomplicated dermatitis, or a short course (duration of 10 days or less or a single injection) of corticosteroid for a non-chronic condition (based on Investigator's clinical judgment) at least 2 weeks prior to enrolment in this study.
- •Any clinically significant acute or chronic medical condition that is considered progressive or in the opinion of the Investigator makes the participant unsuitable for participation in the study; Note: All chronic conditions must be considered stable, there can be no significant change of medications within the previous 2 months, and for diabetics HgbA1c must be \<10%.
- •History of substance abuse or alcohol abuse;
- •Reported behavior that puts the participant at risk for HIV infection within 6 months prior to screening, as defined by:
- •Unprotected sexual intercourse with a known HIV-infected person, a partner known to be at high risk for HIV infection, or a casual partner (ie, no continuing established relationship)
- •Engaged in sex work
- •Frequent excessive daily alcohol use or frequent binge drinking, or any other use of illicit drugs
- •History of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus-2, chlamydia, pelvic inflammatory disease, trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B-or hepatitis C;
- •Three or more sexual partners
Outcomes
Primary Outcomes
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: 9 months
* Proportion of participants with local and systemic solicited Adverse Events (AEs) from Day 1 to Day 7 inclusive after each IP administration * Proportion of participants with Grade 2 or higher unsolicited Adverse Events (AEs), including safety laboratory (biochemical, hematological) parameters from the day of each IP administration through 28 days after each IP administration (any event AND any possibly, probably, or definitely related event) * Proportion of participants with Serious Adverse Events (SAEs) throughout the study period (any event AND any possibly, probably, or definitely related event) * Proportion of participants with Medical Attended Adverse Events (MAAEs) from the first day of IP administration through 24 weeks post final IP administration
Secondary Outcomes
- Immunogenicity(10 months)