| Protocol No: | ECCT/20/07/02 | Date of Protocol: | 29-02-2020 |
| Study Title: |
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
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| Study Objectives: |
PRIMARY
Assess the safety and tolerability (including reactogenicity) of Env-C Plasmid DNA given IM,
alone, admixed with ALF43 adjuvant, topically applied with dmLT adjuvant, or given with an
adjuvanted HIV Env gp145 C.6980 protein and followed by adjuvanted HIV Env gp145
C.6980 protein boost IM immunizations, with or without Env-C Plasmid DNA.
2.6.2 SECONDARY
1. Determine whether the adjuvants under study improve the immunogenicity of
the Env-C Plasmid DNA priming.
2. Determine whether the addition of ALF43 to the Rehydragel® –HIV Env
gp145 C.6980 protein boost further improves the immune response to HIV Env
gp145 C.6980 protein.
3. Determine whether adjuvants improve humoral responses across vaccination
regimens.
4. Evaluate the influence of various adjuvants on cellular immune responses.
5. Describe mucosal humoral responses across vaccination regimens in
cervicovaginal and rectal secretions and semen.
2.6.3 EXPLORATORY
1. Characterize B-cell functional specificities for each vaccination regimen.
2. Characterization of innate immunity.
3. Assess the innate/gene expression induced across vaccination regimens (DNA
microarray, RNA sequencing) to compare relative influence of various
adjuvants in the gene expression profiles of sorted T cell, B cell and innate cell
subsets.
4. Perform systems serology analyses.
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| Laymans Summary: |
The Kenya Medical Research Institute (KEMRI) in collaboration with the U.S. Military HIV
Research Program (MHRP) is conducting a study on HIV vaccines. A vaccine is a medical product
given to prevent certain diseases, most often infectious diseases. The vaccine may educate the
human body to form a defensive response to try to prevent the disease from the beginning or taking
hold of the body. This defensive response called the immune response, and it is the body’s way
to fight infections.
The experimental HIV vaccines tested in this study are Env-C Plasmid DNA and HIV Env gp145
C.6980 protein given with different adjuvants to increase the immune response. An adjuvant is a
substance added to vaccines that can help to make the vaccine more effective by improving the
immune response or causing the immune response to last longer than without the adjuvant. These
adjuvants are mixed with the vaccines and injected into the muscle or placed on top of the skin.
The HIV vaccines contain a piece of genetic material or a protein copied from 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 long
the effects of study vaccines last. This study will also compare the effects (both good and bad) of
the study vaccines with adjuvants and adjuvant patch to those of placebo injections and adjuvant
patch. The placebo will consist of saline (sterile saltwater), look just like the study vaccines with
adjuvants and will be given the same way, but will have no active vaccine or adjuvant in it.
Study objectives will be met by the testing of blood samples from all participants. Willing and
eligible participants have the option to provide lymph node and mucosal secretion samples (semen,
cervicovaginal, rectal) will provide the data for objectives 2 and the sub-objections.
The sponsor of this study is National Institute of Allergy and Infectious Diseases (NIAID) Division
of AIDS (DAIDS), and the Military HIV Research Program (MHRP), a part of the Walter Reed
Army Institute of Research (WRAIR), funds it. A total of 126 participants will take part in this
study.
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| Abstract of Study: |
A safe and effective HIV vaccine would be the cornerstone for cost-effective, user-independent
prevention methods against HIV infection. Most of the successfully licensed vaccines for
prevention of infections have historically relied upon aluminum salt (alum) formulations as
adjuvants because they generally improve protective antibody magnitudes over the vaccine antigen
alone and are reliably safe.
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 at the KEMRI/US Army Medical Research Directorate-Africa
(USAMRD-A), Clinical Research Centre, Kericho; and 126 healthy adults will be enrolled.
Participants enroll randomly into one of seven groups which have 15/3 vaccine/placebo recipients
per group. Each participant will receive six injections (prime at week 0, 4, 12; boost at week 20,
32 and 56) followed up for a total of 108 weeks.
Study objectives will be met by the testing of blood samples from all participants. Willing and
eligible participants have the option to provide lymph node and mucosal secretion samples (semen,
cervicovaginal, rectal), which will provide the data for objectives 2 and the sub-objections.
Exploratory objectives may be met by genetic analysis including but not limited to Human
Leukocyte Antigen (HLA) subtyping.
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