HIV InfectionPhase 1/2NCT01473810
Intranasal Modified Vacc-4x Gag Peptides With Endocine as Adjuvant
A Phase 1/2 study testing Vacc-4x low dose, Vacc-4x medium dose and Vacc-4x high dose in people with HIV Infection, run by Oslo University Hospital at 1 site in Norway.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HIV Infection
- What is being tested?
- Vacc-4x low dose, Vacc-4x medium dose and Vacc-4x high dose
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteNorway
- Study dates
- Nov 2011to Mar 2012
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Norway1 site
Department of Infectious Diseases, Oslo University Hospital
Oslo, NO-0450
About this study
Official title: Immunotherapy of HIV-infected Patients: A Single-blinded, Randomized, Immunogenicity, Pilot Study of Intranasal Administration of Vacc-4x With Endocine as Adjuvant
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).
Read the detailed description
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.
- Conditions
- HIV Infection
- Being tested
- Vacc-4x low dose, Vacc-4x medium dose, Vacc-4x high dose, Zero dose
- Keywords
- HIV, vaccination, T cells, mucosal immunity, safety, nasal administration, DTH skin test
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vacc-4x low doseBiological
Also called Vacc-4x, Endocine
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
Vacc-4x medium doseBiological
Also called Vacc-4x, Endocine
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
Vacc-4x high doseBiological
Also called Vacc-4x, Endocine
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
Zero doseBiological
Also called Endocine
300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks
| Study group | Role | What they receive |
|---|---|---|
| Vacc-4x low dose | Experimental | 80 µg Vacc-4x (20 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity Receives: Biological: Vacc-4x low dose |
| Vacc-4x medium dose | Experimental | 400 µg Vacc-4x (100 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity Receives: Biological: Vacc-4x medium dose |
| Vacc-4x high dose | Experimental | 1200 µg Vacc-4x (300 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity Receives: Biological: Vacc-4x high dose |
| Zero dose | Placebo comparator | Adjuvant only, i.e. 300 µl Endocine divided into two administrations, one for each nose cavity Receives: Biological: Zero dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety of intranasal administration of Vacc-4x with Endocine as adjuvant at three different dose levels
Record adverse events including severe adverse events according to GCP
Measured: 2 months after completion of last patient.
Secondary outcomes (3)
Evaluate cellular immune response to Vacc-4x in vivo by Vacc-4x DTH skin test
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
Measured: Up to 2 months after completion of last patient
Evaluate cellular immune response to Vacc-4x in vitro
Measure changes in Vacc-4x-specific T cell proliferation and activation compared with baseline values for each individual participant, i.e. before vaccination
Measured: Up to 6 months after completion of last patient
Evaluate the effect on CD4+ T cell counts and viral load (HIV-1 RNA) in peripheral blood
Measure individual changes in CD4 counts and viral loads at baseline
Measured: Up to 2 months after completion of last patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2011 (estimated)
- Study startNov 2011
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Bionor Immuno AS, Eurocine Vaccines AB
- Responsible party
- Sponsor
- Investigators
- Dag Kvale, Professor/MD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01473810
- Sponsor's protocol ID
- CTN-Vacc-4x/L3-2011/1
- Status last verified
- Jun 2012
- First submitted
- 1 Nov 2011
- Last updated
- 20 Jun 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Brekke K, Lind A, Holm-Hansen C, Haugen IL, Sorensen B, Sommerfelt M, Kvale D. Intranasal administration of a therapeutic HIV vaccine (Vacc-4x) induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial. PLoS One. 2014 Nov 14;9(11):e112556. doi: 10.1371/journal.pone.0112556. eCollection 2014.
PubMed 25398137
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunotherapy of HIV-infected Patients: A Single-blinded, Randomized, Immunogenicity, Pilot Study of Intranasal Administration of Vacc-4x With Endocine as Adjuvant
- ClinicalTrials.gov ID
- NCT01473810
- Acronym / sponsor ID
- CTN-Vacc-4x/L3-2011/1
- Conditions
- HIV Infection
- Keywords
- HIV, vaccination, T cells, mucosal immunity, safety, nasal administration, DTH skin test
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- Bionor Immuno AS, Eurocine Vaccines AB
- Study start
- Nov 2011
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 17 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Vacc-4x low dose | Experimental | Biological: Vacc-4x low dose80 µg Vacc-4x (20 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity |
| Vacc-4x medium dose | Experimental | Biological: Vacc-4x medium dose400 µg Vacc-4x (100 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity |
| Vacc-4x high dose | Experimental | Biological: Vacc-4x high dose1200 µg Vacc-4x (300 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity |
| Zero dose | Placebo comparator | Biological: Zero doseAdjuvant only, i.e. 300 µl Endocine divided into two administrations, one for each nose cavity |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vacc-4x low doseAlso: Vacc-4x, Endocine80 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 | Biological | Vacc-4x low dose |
| Vacc-4x medium doseAlso: Vacc-4x, Endocine400 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 | Biological | Vacc-4x medium dose |
| Vacc-4x high doseAlso: Vacc-4x, Endocine1200 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 | Biological | Vacc-4x high dose |
| Zero doseAlso: Endocine300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks | Biological | Zero dose |
Primary outcome
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
3 secondary outcomes
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
Evaluate cellular immune response to Vacc-4x in vitro
Time frame: Up to 6 months after completion of last patient
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2012.
- Derived from this study: PubMed 25398137Brekke K, Lind A, Holm-Hansen C, Haugen IL, Sorensen B, Sommerfelt M, Kvale D. Intranasal administration of a therapeutic HIV vaccine (Vacc-4x) induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial. PLoS One. 2014 Nov 14;9(11):e112556. doi: 10.1371/journal.pone.0112556. eCollection 2014.
- University of Oslo, Faculty of Medicine, public web page for PILink provided by the sponsor.
- Web page of Vacc-4x vaccine patent holder (not sponsor, peptide supply free of charge, research collaborator)Link provided by the sponsor.
- Web page of adjuvant patent holder (not sponsor, research collaborator, expenses in part covered by Research Council of Norway)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dag Kvale, Professor/MD principal investigator
Oslo University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Vacc-4x low dose, Vacc-4x medium dose and Vacc-4x high dose in people with HIV Infection, run by Oslo University Hospital at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01473810, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2012.