A Randomized, Double-Blind Phase 1 Trial to Evaluate the Safety and Immunogenicity of Priming With Env-C Plasmid DNA Vaccine Alone, With Different Adjuvants, or With an Adjuvanted HIV Env gp145 C.6980 Protein Vaccine and Boosting With the Adjuvanted HIV Env gp145 C.6980 Protein Vaccine With or Without the Env-C Plasmid DNA Vaccine in Healthy HIV Uninfected Adults in Kenya
Overview
- Phase
- Phase 1
- Intervention
- Placebo (IM)
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 143
- Locations
- 1
- Primary Endpoint
- Number of Solicited Local Events Post Vaccination 1 by Priming Dose Group (Outcome 1)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a study of HIV vaccines. A vaccine is a medical product given to prevent certain diseases. The vaccine may educate the body to form a defensive response to try to prevent the disease from the beginning, or preventing it from taking hold of the body. This defensive response is called the immune response. The experimental vaccines in this study are Env-C Plasmid DNA and HIV Env gp145 C690 protein, given with different adjuvants. An adjuvant is a substance added to vaccines that can help make the vaccine more effective by improving the immune response, or by causing the immune response to last longer than it would without the adjuvant. The adjuvants are mixed with the vaccines and injected into muscle or placed on top of the skin. The HIV vaccines contain a piece of genetic material or a protein copied drom the HIV virus cover (Env), but they do not contain the virus itself. The vaccines cannot cause HIV infection or Acquired Immune Deficiency Syndrome (AIDS).
The purpose of this study is to find out if the study vaccines with adjuvants cause side effects and are tolerable, whether humans respond (develop immune responses) to the vaccines, and how ling the effects of the study vaccines last. The study will also compare the effects of the study vaccines with adjuvants and adjuvant patch to those of placebo injections and placebo patch. The placebo will consist of saline (sterile saltwater) and will look like study vaccines, be given in the same way, but will have no active vaccine or adjuvant in it. A total of 126 participants will take part in the study and each will have up to 26 clinic visits and will be followed-up for a total of 108 weeks.
Detailed Description
Antibodies are the most commonly recognized correlate of vaccine protection from infection; however the possible protective HIV antibody levels, which were induced by the modestly protective RV144 vaccine regimen with alum, rapidly decayed. Potentially, a novel, highly selective adjuvant combined with the correctly sequenced HIV antigen could slow antibody decay, increase antibody magnitude and induce antibodies of appropriate functional response. RV460 is an exploratory study that will assess the safety, tolerability, and immunogenicity of a vaccine regimen consisting of priming with an Env-C Plasmid DNA vaccine (with or without novel adjuvants) when given with or without adjuvanted HIV Env gp145 C.6980 protein vaccine and boosting with adjuvanted gp145 C.6980 protein with or without the gp120 DNA vaccine. The study will be carried out in Kericho, Kenya. 126 healthy adults will ben enrolled. Participants will be randomized into one of seven groups which have 15/3 vaccine/placebo recipients per group. Each participant will receive six injections (prim at week 0, 4, 12; boost at week 20, 32 and 56) and will be followed-up for a total of 108 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy, male and female participant aged 18 to 40 years and available for 26 months.
- •Must be at low risk for HIV infection per investigator assessment and using the study risk assessment tool.
- •Must be able to understand and complete the informed consent process.
- •Must be capable of reading English or Kiswahili.
- •Must agree to a home visit.
- •Must complete a Test of Understanding (TOU) before enrollment. Must answer 9 out of 10 questions correctly with a maximum of three attempts.
- •Must be in good general health without a clinically significant medical history.
- •HIV-uninfected per diagnostic algorithm within 45 days of enrollment.
- •Laboratory values:
- •Hemoglobin
Exclusion Criteria
- •A history of:
- •Three or more sexual partners in the previous 24 weeks.
- •Commercial sex work.
- •Non-adherence to condom use in the absence of a long-term monogamous relationship.
- •Intravenous drug use in the previous year.
- •A sexually transmitted infection in the previous 24 weeks.
- •Asplenia: any condition resulting in the absence of a functional spleen.
- •Bleeding disorder diagnosed by a medical doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
- •Breastfeeding or pregnant (positive pregnancy test) women or planning to become pregnant during the window between study enrollment and three months after the last vaccination visit.
- •Any past, ongoing, or in remission history of treated or untreated autoimmune disease.
Arms & Interventions
Group 2: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Placebo (IM)
Group 3: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Env-C Plasmid DNA
Group 3: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: HIV Env gp145 C.6980 protein
Group 3: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Rehydragel®
Group 1: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Env-C Plasmid DNA
Group 1: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: HIV Env gp145 C.6980 protein
Group 1: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Rehydragel®
Group 1: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Placebo (IM)
Group 2: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Env-C Plasmid DNA
Group 2: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: HIV Env gp145 C.6980 protein
Group 2: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Rehydragel®
Group 2: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: ALF43
Group 3: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: dmLT
Group 3: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Placebo (IM)
Group 3: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Placebo (TCl)
Group 4: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Env-C Plasmid DNA
Group 4: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: HIV Env gp145 C.6980 protein
Group 4: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Rehydragel®
Group 4: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: ALF43
Group 4: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: dmLT
Group 4: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Placebo (IM)
Group 4: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Placebo (TCl)
Group 5: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Env-C Plasmid DNA
Group 5: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: HIV Env gp145 C.6980 protein
Group 5: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Rehydragel®
Group 5: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: ALF43
Group 5: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Placebo (IM)
Group 6: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Env-C Plasmid DNA
Group 6: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: HIV Env gp145 C.6980 protein
Group 6: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Rehydragel®
Group 6: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: ALF43
Group 6: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Placebo (IM)
Group 7: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Env-C Plasmid DNA
Group 7: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: HIV Env gp145 C.6980 protein
Group 7: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Rehydragel®
Group 7: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: ALF43
Group 7: Vaccine
3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56
Intervention: Placebo (IM)
Pooled Placebo
Pooled placebo arm.
Intervention: Placebo (TCl)
Outcomes
Primary Outcomes
Number of Solicited Local Events Post Vaccination 1 by Priming Dose Group (Outcome 1)
Time Frame: Day 1-Day 7 Post Vaccination 1
Incidence (number and percentage of participants) of local reactogenicity events post dose 1 by symptom, maximum severity, and priming dose group
Number of Solicited Local Events Post Vaccination 2 by Priming Dose Group (Outcome 2)
Time Frame: Day 1-Day 7 Post Vaccination 2
Incidence (number and percentage of participants) of local reactogenicity events post dose 2 by symptom, maximum severity, and priming dose group
Number of Solicited Local Events Post Vaccination 3 by Priming Dose Group (Outcome 3)
Time Frame: Day 1-Day 7 Post Vaccination 3
Incidence (number and percentage of participants) of local reactogenicity events post dose 3 by symptom, maximum severity, and vaccination group.
Number of Solicited Local Events Post Vaccination 4 by Vaccination Group (Outcome 4)
Time Frame: Day 1-Day 7 Post Vaccination 4
Incidence (number and percentage of participants) of local reactogenicity events post dose 4 by symptom, maximum severity, and vaccination group
Number of Solicited Local Events Post Vaccination 5 by Vaccination Group (Outcome 5)
Time Frame: Day 1-Day 7 Post Vaccination 5
Incidence (number and percentage of participants) of local reactogenicity events post dose 5 by symptom, maximum severity, and priming dose group
Number of Solicited Local Events Post Vaccination 6 by Vaccination Group (Outcome 6)
Time Frame: Day 1-Day 7 Post Vaccination 6
Incidence (number and percentage of participants) of local reactogenicity events post dose 6 by symptom, maximum severity, and vaccination group
Number of Solicited Systemic Events Post Vaccination 1 by Priming Dose Group (Outcome 7)
Time Frame: Day 1-Day 7 Post Vaccination 1
Incidence (number and percentage of participants) of systemic reactogenicity events post dose 1 by symptom, maximum severity, and priming dose group
Number of Solicited Systemic Events Post Vaccination 2 by Priming Dose Group (Outcome 8)
Time Frame: Day 1-Day 7 Post Vaccination 2
Incidence (number and percentage of participants) of systemic reactogenicity events post dose 2 by symptom, maximum severity, and priming dose group
Number of Solicited Systemic Events Post Vaccination 3 by Priming Dose Group (Outcome 9)
Time Frame: Day 1-Day 7 Post Vaccination 3
Incidence (number and percentage of participants) of systemic reactogenicity events post dose 3 by symptom, maximum severity, and vaccination group
Number of Solicited Systemic Events Post Vaccination 4 by Vaccination Group (Outcome 10)
Time Frame: Day 1-Day 7 Post Vaccination 4
Incidence (number and percentage of participants) of systemic reactogenicity events post dose 4 by symptom, maximum severity, and vaccination group
Number of Solicited Systemic Events Post Vaccination 5 by Vaccination Group (Outcome 11)
Time Frame: Day 1-Day 7 Post Vaccination 5
Incidence (number and percentage of participants) of systemic reactogenicity events post dose 5 by symptom, maximum severity, and priming dose group
Number of Solicited Systemic Events Post Vaccination 6 by Vaccination Group (Outcome 12)
Time Frame: Day 1-Day 7 Post Vaccination 6
Incidence (number and percentage of participants) of systemic reactogenicity events post dose 6 by symptom, maximum severity, and vaccination group
Number of Related Unsolicited AEs (Outcome 13)
Time Frame: Day 1-Day 728
Incidence (number and percentage of participants) of related unsolicited AEs by maximum severity and vaccination group.
Number of SAEs (Outcome 14)
Time Frame: Day 1-Day 728
Incidence (number and percentage of participants) of SAEs by maximum severity and vaccination group
Secondary Outcomes
- Magnitude of Plasma IgG Binding Antibodies in Response to Differing DNA Priming Regimens(Thru Week 105)
- Durability of Plasma IgG Binding Antibodies in Response to Differing DNA Priming Regimens(Thru Week 105)
- Area Under the Curve (AUC) for Plasma IgG Binding Antibodies in Response to Differing DNA Priming Regimens(Thru Week 105)
- Magnitude of Plasma IgG Binding Antibodies Between Groups With and Without Rehydragel® After HIV Env gp145 C.6980 Protein Boosting(Thru Week 105)
- Durability of Plasma IgG Binding Antibodies Between Groups With and Without Rehydragel® After HIV Env gp145 C.6980 Protein Boosting(Thru Week 105)
- AUC for Plasma IgG Binding Antibodies Between Groups With and Without Rehydragel® After HIV Env gp145 C.6980 Protein Boosting(Thru Week 105)
- Presence of Plasma IgG Binding Antibodies(Thru Week 105)
- Presence of Plasma IgA Binding Antibodies(Thru Week 105)
- Types of Cell-mediated Immune Responses(Thru Week 105)
- Level of Cell-mediated Immune Responses(Thru Week 105)
- Types of Mucosal Humoral Responses(Thru Week 104)