A Clinical Trial to Evaluate Safety, Tolerability, and Immunogenicity of Adjuvanted HIV-1 Fusion Peptide Conjugate Vaccine Alone or in Prime-Boost Regimens With Adjuvanted HIV-1 Envelope Trimer 4571 and HIV-1 Trimer 6931 Vaccines in Healthy Adults
- Conditions
- HIV
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 44
Inclusion Criteria:<br><br> 1. Able and willing to complete the informed consent process, including an Assessment<br> of Understanding (AoU): volunteer demonstrates understanding of this study,<br> completes a questionnaire prior to first vaccination with verbal demonstration of<br> understanding of all questionnaire items answered incorrectly.<br><br> 2. 18-50 years old, inclusive, on day of enrollment.<br><br> 3. Agrees to comply with planned study procedures and be available for clinic follow-up<br> through the last clinic visit.<br><br> 4. Agrees not to enroll in another study of an investigational agent during<br> participation in the trial, including severe acute respiratory syndrome coronavirus<br> 2 (SARS-CoV-2) investigational agents that may subsequently obtain emergency use<br> authorization (EUA) or undergo licensure by the FDA. If a potential participant is<br> already enrolled in a SARS-CoV-2 clinical trial, prior approvals from the SARS-COV-2<br> study sponsor and HVTN 303 PSRT are required prior to enrollment in HVTN 303.<br><br> 5. In good general health without clinically significant medical history.<br><br> 6. Physical examination and laboratory results without clinically significant findings<br> that would interfere with assessment of safety or reactogenicity.<br><br> 7. Body Mass Index (BMI) = 40.<br><br> 8. Assessed as low risk for HIV acquisition.<br><br> 9. Suitable injection sites in the deltoid muscle of each arm, as assessed by a<br> clinician.<br><br> 10. White blood cells (WBCs) 2,500-12,000/mm3<br><br> 11. WBC differential either within institutional normal range or approved by the<br> Investigator of Record (IoR) as not clinically significant.<br><br> 12. Platelets = 125,000 - 500,000/mm3<br><br> 13. Hemoglobin<br><br> - = 11.0 g/dL for volunteers who were assigned female sex at birth<br><br> - = 13.0 g/dL for volunteers who were assigned male sex at birth and transgender<br> males who have been on hormone therapy for more than 6 consecutive months<br><br> - = 12.0 g/dL for transgender females who have been on hormone therapy for more<br> than 6 consecutive months<br><br> - For transgender participants who have been on hormone therapy for less than 6<br> consecutive months, determine hemoglobin eligibility based on the sex assigned<br> at birth<br><br> 14. Serum creatinine = 1.1 x upper limit of normal (ULN) based on the institutional<br> normal range.<br><br> 15. Alanine aminotransferase (ALT) =1.25 x ULN based on the institutional normal range.<br><br> 16. Negative for HIV infection by an (US) Food and Drug Administration (FDA)-approved<br> enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA).<br><br> 17. Negative for anti-Hepatitis C antibodies (anti-HCV) or negative HCV nucleic acid<br> test (NAT) if anti-HCV antibodies are detected.<br><br> 18. Negative for Hepatitis B surface antigen.<br><br> 19. Agrees to use effective means of birth control from at least 21 days prior to<br> enrollment through 12 weeks after the last product administration.<br><br> 20. Negative ß-HCG (beta human chorionic gonadotropin) pregnancy test (urine or serum)<br> at screening and prior to each study product administration on the day of study<br> product administration.<br><br>Exclusion Criteria:<br><br> 1. Active duty and reserve US military personnel.<br><br> 2. Breast-feeding or planning to become pregnant from at least 21 days prior to<br> enrollment through 12 weeks after the last product administration.<br><br> 3. An investigational HIV vaccine (previous placebo recipients are not excluded).<br><br> 4. Immunosuppressive medications received within 168 days before first vaccination (Not<br> exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3]<br> topical corticosteroids for mild, uncomplicated dermatologic condition; or [4] a<br> single course of oral/parenteral prednisone or equivalent at doses = 60 mg/day and<br> length of therapy < 11 days with completion at least 30 days prior to enrollment).<br><br> 5. Blood products within 60 days prior to enrollment<br><br> 6. Monoclonal antibodies (mAbs), whether licensed or investigational. Exceptions may be<br> made by the HVTN 303 PSRT on a case-by-case basis<br><br> 7. Receipt of any of the following:<br><br> - Within 4 weeks prior to enrollment:<br><br> - Any licensed live, attenuated vaccine<br><br> - Any adenoviral-vectored SARS-CoV-2 vaccine with FDA Emergency Use<br> Authorization (EUA), FDA licensure or World Health Organization (WHO)<br> Emergency Use Listing (EUL)<br><br> - Within 2 weeks prior to enrollment:<br><br> - Any licensed killed/subunit/inactivated vaccine<br><br> - Any mRNA based or protein SARS-CoV-2 vaccines with FDA EUA, FDA licensure,<br> or WHO EUL<br><br> 8. Investigational research agents with a half-life of 7 or fewer days within 4 weeks<br> prior to enrollment. If a potential participant has received investigational agents<br> with a half-life greater than 7 days (or unknown half-life) within the past year,<br> PSRT approval is required for enrollment.<br><br> 9. Current allergen immunotherapy with antigen injections, unless on maintenance<br> schedule.<br><br> 10. Current anti-TB prophylaxis or therapy.<br><br> 11. Serious adverse reactions to vaccines or vaccine components.<br><br> 12. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.<br><br> 13. Hypertension that is not well controlled.<br><br> 14. Asthma is excluded if the participant has ANY of the following:<br><br> - Required either oral or parenteral corticosteroids for an exacerbation two or<br> more times within the past year; OR<br><br> - Needed emergency care, urgent care, hospitalization, or intubation for an acute<br> asthma exacerbation within the past year (eg, would NOT exclude individuals<br> with asthma who meet all other criteria but sought urgent/emergent care solely<br> for asthma medication refills or co-existing conditions unrelated to asthma);<br> OR<br><br> - Uses a short-acting rescue inhaler more than 2 days/week for acute asthma<br> symptoms (ie, not for preventive treatment prior to athletic activity); OR<br><br> - Uses medium-to-high-dose inhaled corticosteroids (greater than 250 mcg<br> fluticasone or therapeutic equivalent per day), whether in single-therapy or<br> dual-therapy inhalers (ie, with a long-acting beta agonist [LABA]); OR<br><br> - Uses more than one medication for maintenance therapy daily. Inclusion of<br> anyone on a stable dose of more than one medication for maintenance therapy<br> daily for greater than two years requires PSRT approval.<br><br> 15. Autoimmune disease, current or history, including psoriasis.<br><br> 16. Clinically significant immunodeficiency.<br><br> 17. AESIs: Volunteers who currently have, or have a history of, any condition that could<br> be considered an AESI for the product(s) administered in this protocol.<br><br> 18. History of generalized urticaria, angioedema, or anaphylaxis. (Not exclusionary:<br> angioedema or anaphylaxis to a known trigger with at least 5 years since last<br> reaction to demonstrate satisfactory avoidance of trigger.).<br><br> 19. Diabetes mellitus type 1 or type 2.<br><br> 20. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or<br> platelet disorder requiring special precautions) or significant bruising or bleedin
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Local reactogenicity signs and symptoms collected for all participants;Systemic reactogenicity signs and symptoms collected for all participants;Adverse events collected for all participants;Magnitude of serum antibody binding of FP and envelope trimer antigens as measured by the MSD assay 2 weeks after the last vaccination.;Response rate of serum antibody binding of FP and envelope trimer antigens as measured by the MSD assay 2 weeks after the last vaccination.
- Secondary Outcome Measures
Name Time Method Magnitude of serum antibody neutralization, as measured by the TZM-bl assay.;Response rate of serum antibody neutralization, as measured by the TZM-bl assay.;Breadth of serum antibody neutralization, as measured by the TZM-bl assay.;Magnitude of serum IgG binding antibodies to FP, Trimer 4571, and Trimer 6931.;Response rate of serum IgG binding antibodies to FP, Trimer 4571, and Trimer 6931.;Mapping of FP specific serum neutralizing activity via characterization of specific epitopes (such as base of trimers, V3, internal epitopes).;Magnitude of CD4+ T-cell responses as assessed by intracellular cytokine staining assays (ICS).;Response rate of CD4+ T-cell responses as assessed by intracellular cytokine staining assays (ICS).