Intranasal Modified Vacc-4x Gag Peptides With Endocine as Adjuvant
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| ClinicalTrials.gov Identifier: NCT01473810 |
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Recruitment Status :
Completed
First Posted : November 17, 2011
Last Update Posted : June 20, 2012
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HIV-specific cellular immunity is hampered in most HIV-infected individuals. Therapeutic immunization in HIV aims to strengthen the HIV-specific cellular immunity, usually in the absence of replicating HIV with antiretroviral drugs. The aims of this strategy can be to decrease the mass of latently infected CD4+ T cells, better tolerance of drug-free periods, and better select candidates for preventive HIV vaccines.
Vacc-4x is one of the few peptide-based therapeutic vaccines tested, and consists of four, slightly modified HIV Gag p24 consensus peptides. Vacc-4x was first tested by intradermal injections using GM-CSF as adjuvant. A recent multinational placebo-controlled study found improvement of vaccine-specific T cell immunity and decrease in viral loads (presented at the AIDS vaccine 2011 conference, Bangkok).
In this study the investigators hypothesize that the Vacc-4x peptides, deposited on the nasal mucosal surfaces in conjunction with Endocine, a newly developed and documented mucosal adjuvant, will induce T cell responses to HIV and improve HIV-specific immunity both systemically and at mucosal surfaces (oral, rectal, vaginal).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HIV Infection | Biological: Vacc-4x low dose Biological: Vacc-4x medium dose Biological: Vacc-4x high dose Biological: Zero dose | Phase 1 Phase 2 |
HIV-specific cellular immunity is hampered in most HIV-infected individuals, partly because the virus infects CD4+ T cells, the key cell subset in all immune responses. CD4 is the primary HIV receptor (CD4), but infection requires a co-receptor (CCR5) which is carried mainly by activated T cells. During primary HIV-infection, two types of CD4+ T cells mainly become infected: (i) Sub-activated T cells of all specificities within the mucosal linings, particularly in the gut; and (ii) HIV-specific T cell clones, that proliferates and are activated as a normal response to HIV infection itself. The HIV-specific immunity therefore becomes severely compromised early in the infection. Patients having better T cells specific to parts of the HIV Gag matrix protein usually progress slower towards AIDS than patients with poor T cell responsitivity towards Gag.
Therapeutic immunization in HIV aims to strengthen the HIV-specific cellular immunity, usually in the absence of replicating HIV with antiretroviral drugs. The aims of this strategy can be to decrease the mass of latently infected CD4+ T cells, better tolerance of drug-free periods, and better select candidates for preventive HIV vaccines. The latter point may be important since clinical trials with preventive vaccine candidates may challenge our ethical standards: Such trials must be very large and conducted in poor areas with high prevalence of HIV, in order to have as many (placebo) or few (vaccine candidate) new HIV infections as fast as possible. Preventive vaccine trials might therefore compete with introduction of "western" access to HIV drugs.
Vacc-4x is one of the few peptide-based therapeutic vaccines tested, and consists of four, slightly modified HIV Gag p24 consensus peptides. Vacc-4x was first tested by intradermal injections using GM-CSF as adjuvant. In a dose study at our Hospital, the investigators found induction of robust cellular immune responses both in vitro and in vivo by skin testing, indications of improved viral control, long-lasting immunity and lack of mutational changes in the HIV strains within the study cohort. A recently completed multinational placebo-controlled study found improvement of viral loads (presented at the AIDS vaccine 2011 conference, Bangkok).
In this study the investigators hypothesize that the Vacc-4x peptides, deposited on the nasal mucosal surfaces in conjunction with Endocine, a newly developed and documented mucosal adjuvant, will induce T cell responses to HIV and improve HIV-specific immunity both systemically and at mucosal surfaces (oral, rectal, vaginal). This route of application may even simplify mass vaccination. The study is primarily a dose-study focused on adverse events, which have been negligible when Vacc-4x was given parenterally, as well as induction of systemic and mucosal immunity.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 24 participants |
| Allocation: | Randomized |
| Intervention Model: | Factorial Assignment |
| Masking: | Single (Participant) |
| Primary Purpose: | Treatment |
| Official Title: | Immunotherapy of HIV-infected Patients: A Single-blinded, Randomized, Immunogenicity, Pilot Study of Intranasal Administration of Vacc-4x With Endocine as Adjuvant |
| Study Start Date : | November 2011 |
| Actual Primary Completion Date : | March 2012 |
| Actual Study Completion Date : | March 2012 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Vacc-4x low dose
80 µg Vacc-4x (20 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity
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Biological: Vacc-4x low dose
80 µg Vacc-4x (20 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks
Other Names:
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Experimental: Vacc-4x medium dose
400 µg Vacc-4x (100 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity
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Biological: Vacc-4x medium dose
400 µg Vacc-4x (100 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks
Other Names:
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Experimental: Vacc-4x high dose
1200 µg Vacc-4x (300 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity
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Biological: Vacc-4x high dose
1200 µg Vacc-4x (300 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks
Other Names:
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Placebo Comparator: Zero dose
Adjuvant only, i.e. 300 µl Endocine divided into two administrations, one for each nose cavity
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Biological: Zero dose
300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks
Other Name: Endocine |
- Evaluate the safety of intranasal administration of Vacc-4x with Endocine as adjuvant at three different dose levels [ Time Frame: 2 months after completion of last patient. ]Record adverse events including severe adverse events according to GCP
- Evaluate cellular immune response to Vacc-4x in vivo by Vacc-4x DTH skin test [ Time Frame: Up to 2 months after completion of last patient ]Record intradermal Vacc-4x-associated delayed-type hypersensitivity test (DTH) in vivo by measuring skin induration (area) 2 days after injecion qt end of study week 8, in comparison with 38 historical unvaccinated HIV seropositive controls
- Evaluate cellular immune response to Vacc-4x in vitro [ Time Frame: Up to 6 months after completion of last patient ]Measure changes in Vacc-4x-specific T cell proliferation and activation compared with baseline values for each individual participant, i.e. before vaccination
- Evaluate the effect on CD4+ T cell counts and viral load (HIV-1 RNA) in peripheral blood [ Time Frame: Up to 2 months after completion of last patient ]Measure individual changes in CD4 counts and viral loads at baseline
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| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age above 18 years, both genders.
- HIV positive at least one year.
- Clinically stable on ART for the last 6 months (changes in therapy is allowed as long as the viral load is stable).
- Documented viral load (HIV-1 RNA) less than 50 copies/mL for the last six months.
- Documented stable CD4 cell count ≥ 400x106/L.
- Nadir (lowest ever) CD4 cell count ≥ 200x106/L.
- Signed informed consent.
Exclusion Criteria:
- Reported pre-study AIDS-defining illness within the previous year.
- Malignant disease.
- On chronic treatment with immunosuppressive therapy.
- Unacceptable values of the hematologic and clinical chemistry parameters, as judged by the Principle Investigator (or designee), including creatinine values >1.5x upper limit of normal (ULN), and AST (SGOT), ALT (SGPT) and alkaline phosphatase values >2.5x ULN.
- Concurrent chronic active infection such as chronic viral hepatitis B or C or active tuberculosis.
- Pregnant or breastfeeding women.
- Women of childbearing potential not using reliable and adequate contraceptive methods (defined as: use of oral, implanted, injectable, mechanical or barrier products for the prevention of pregnancy; practicing abstinence; sterile) during the study, or sexually active male patients with partners of childbearing potential unwilling to practice effective contraception during the study.
- Current participation in other clinical therapeutic studies.
- Incapability of compliance to the treatment protocol, in the opinion of the Investigator.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01473810
| Norway | |
| Department of Infectious Diseases, Oslo University Hospital | |
| Oslo, Norway, NO-0450 | |
| Principal Investigator: | Dag Kvale, Professor/MD | Oslo University Hospital |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Oslo University Hospital |
| ClinicalTrials.gov Identifier: | NCT01473810 |
| Other Study ID Numbers: |
CTN-Vacc-4x/L3-2011/1 |
| First Posted: | November 17, 2011 Key Record Dates |
| Last Update Posted: | June 20, 2012 |
| Last Verified: | June 2012 |
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HIV vaccination T cells mucosal immunity |
safety nasal administration DTH skin test |
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HIV Infections Blood-Borne Infections Communicable Diseases Infections Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Lentivirus Infections Retroviridae Infections RNA Virus Infections |
Virus Diseases Genital Diseases Urogenital Diseases Immunologic Deficiency Syndromes Immune System Diseases Endocine Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs |