HIV InfectionsPhase 1ISST-001NCT00505401
Phase I Safety and Immunogenicity Vaccine Trial Against HIV/AIDS
A Phase 1 study testing recombinant HIV-1 Tat protein in people with HIV Infections, run by Istituto Superiore di Sanità at 4 sites in Italy.
Trial summary
The development of a vaccine against HIV/AIDS has been primary focused on the structural proteins (Env, Gag) of HIV-1 with the aim of inducing sterilizing immunity by blocking virus entry. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- recombinant HIV-1 Tat protein
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 4 sitesItaly
- Study dates
- Dec 2003to Nov 2007
- Phase
- Phase 1
- 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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Negative pregnancy test for women of childbearing potential within 3 days prior to baseline evaluation and use of an acceptable means of contraception (condom, hormonal or mechanical method) for one month prior to immunization and the duration of the study;
- Clinically asymptomatic HIV-1 infected individuals (CDC Clinical category A), as determined by two positive Enzyme-linked immunosorbent assay (ELISA) and a confirmatory Western Blot;
- Mean CD4+ T cell count >= 400 cells/microL based on 2 separate determinations, at least 2 weeks apart, within the four weeks pre-study screening period. [Note: If one of the two values is < 400 the patient will be excluded. Patients ever having had a value of CD4+ T cell number < 250 will be excluded];
- Plasma HIV-1 viremia levels <= 50,000 copies/mL;
- Complete blood count and differential defined as:
- Hematocrit >= 30% for women, >= 38% for men
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- Hemoglobin >= 9.5 g/dL
- White cell counts >= 4,000 cells/mm3
- Total lymphocyte count >= 1000 cells/mm3
- Platelets >= 100,000/mm3
- Differential within institutional normal limits or approval of site physician
- Normal ALT (as defined by the range of the clinical site laboratories) and Creatinine (<= 1.6 mg/dL);
- Normal urine dipstick with esterase and nitrite;
- Normal thyroid function;
- Availability for follow-up for planned duration of at least 12 months and willing to have further brief evaluations at 24 and 36 months;
- Signed informed consent.
Who cannot join
- History of AIDS-related opportunistic or neoplastic disease;
- History of encephalopathy, neuropathy, or unstable CNS pathology (HIV or non-HIV related);
- History of non-HIV related neoplastic diseases, autoimmune diseases, angina or cardiac arthymias, or any other clinically significant medical problems;
- Chest radiography showing evidence of active or acute cardiac or pulmonary disease;
- History of anaphylaxis or serious adverse reactions to vaccines as well as serum IgE levels exceeding 1000 U.I./mL;
- History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g. Steven-Johnson syndrome, bronchospasm, or hypotension);
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- Active syphilis [NOTE. If the serology is documented to be a false positive or due to an adequately treated infection, the volunteer is eligible];
- Active tuberculosis [NOTE: Volunteers with a positive PPD and a normal chest X-ray showing no evidence of TB and not requiring isoniazid (INH) therapy are eligible];
- Medical or psychiatric condition or occupational responsibilities which preclude subject compliance with the protocol. Specifically excluded are persons with psychotic disorders, major affective disorders, suicidal ideation;
- Current use of psychotrophic drugs;
- Use of antiretroviral therapy within 3 months of pre-study screening.
- Use of any experimental HIV therapy or participation in another experimental protocol within three (3) months of pre-study screening;
- Current or prior therapy with immunomodulators or immunosuppressive drugs and anticoagulant drugs within 30 days prior to study medication administration;
- Any unstable cardio-vascular disease (e.g unstable hypertensive disease needing modification or introduction of an anti-hypertensive treatment);
- Live attenuated vaccines within 60 days of study [NOTE: Medically indicated sub-unit or killed vaccines (e.g., influenza, pneumococcal, hepatitis A and B) are not exclusionary, but should be given at least 4 weeks away from HIV immunizations];
- Receipt of blood products or immunoglobulin in the past year;
- Prior receipt of HIV-1 vaccine in a previous HIV vaccine trial;
- Positivity for HBV antigens (HBs Ag, HBe Ag), and HCV, HTLV-I and HTLV-II antibodies;
- Positivity for HHV-8 antibodies and plasmaviremia (volunteers will be screened for anti-HHV-8 antibodies and positivity confirmed by PCR, only the individuals confirmed positive by PCR will be excluded);
- Pregnant or lactating women.
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
San Raffaele Hospital
Milan, 20132
Hospital Spallanzani
Rome, 00149
San Gallicano Hospital
Rome, 00153
University of Rome "La Sapienza"
Rome, 00161
About this study
Official title: A Phase I Safety and Immunogenicity Trial of Recombinant HIV-1 Tat in HIV-1 Infected Adult Volunteers
The development of a vaccine against HIV/AIDS has been primary focused on the structural proteins (Env, Gag) of HIV-1 with the aim of inducing sterilizing immunity by blocking virus entry. Alternative approaches are focused on new vaccine strategies aimed at modifying the virus-host dynamic favouring the establishment of a long-term non-progressing disease status. Such strategies target regulatory proteins that are the first to be expressed after infection and are essential for viral replication, infectivity and pathogenesis. Thus, this approach may be effective for both preventive and therapeutic vaccination strategies.
Read the detailed description
Being a very early viral regulatory protein necessary for viral gene expression, cell-to-cell virus transmission and disease progression, Tat represents a key target protein for the host immune response and an optimal candidate for such a vaccination strategy.
Preclinical studies demonstrated that vaccination with a biologically active Tat protein is safe, elicits a broad and specific immune response and induces a long-term protection against infection. Cross-sectional and longitudinal studies in natural infection suggest that the presence of an anti-Tat humoral immune response correlates with asymptomatic infection and with a slower disease progression while the presence of CD8+ T cell responses to Tat correlate with early virus control both in humans and monkeys. Since the immunogenic regions of Tat are well conserved among the HIV-1 M group, a vaccine based on Tat may be used in different geographic areas of the world.
This Phase I study was directed at evaluating the safety profile (as a primary end-point) and the immunogenicity (as a secondary end-point) of the recombinant HIV-1 Tat vaccine in HIV-1 infected adult volunteers with mild immune deficiency (Clinical category A according to CDC), CD4+ T cell counts 400/mL and levels of plasma viremia < 50,000 copies/mL.
Study Design: Randomized, Double Blind, Placebo Controlled, Safety/Immunogenicity Study.
- Conditions
- HIV Infections
- Being tested
- recombinant HIV-1 Tat protein
- Keywords
- HIV, Tat protein, HIV Therapeutic Vaccine
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant HIV-1 Tat proteinBiological
| Study group | Role | What they receive |
|---|---|---|
| A | Other | Subjects were immunized subcutaneously with Tat, 3 dosage groups (7.5, 15 or 30 microgrammi), in association with Alum as adjuvant, or with Saline + Alum, as placebo. Receives: Biological: recombinant HIV-1 Tat protein |
| B | Other | Subjects were immunized intradermally with Tat, 3 dosage groups (7.5, 15 or 30 microgrammi), or with Saline, as placebo. Receives: Biological: recombinant HIV-1 Tat protein |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of product safety included clinical monitoring of volunteers for local and systemic adverse reactions during the course of the trial and monitoring of haematological, biochemical, virological and immunological parameters
Secondary outcomes (1)
To qualify Tat protein as immunogenic, volunteers were monitored for anti-Tat specific antibodies (IgM, IgG, IgA), anti-Tat proliferative response and in vitro γIFN and IL-4 production by PBMC before vaccination and in response to Tat vaccine.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2007 (estimated)
- Study startDec 2003
- Study completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Superiore di Sanità
- Sponsor type
- University, hospital or other
- Investigators
- Barbara Ensoli, MD, PhD, Study director, National AIDS Center, Istituto Superiore di Sanità, Rome, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00505401
- Sponsor's protocol ID
- ISST-001
- Acronym
- ISST-001
- Status last verified
- Jul 2007
- First submitted
- 20 Jul 2007
- Last updated
- 1 Mar 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ensoli B, Fiorelli V, Ensoli F, Cafaro A, Titti F, Butto S, Monini P, Magnani M, Caputo A, Garaci E. Candidate HIV-1 Tat vaccine development: from basic science to clinical trials. AIDS. 2006 Nov 28;20(18):2245-61. doi: 10.1097/QAD.0b013e3280112cd1. No abstract available.
PubMed 17117011Rezza G, Fiorelli V, Dorrucci M, Ciccozzi M, Tripiciano A, Scoglio A, Collacchi B, Ruiz-Alvarez M, Giannetto C, Caputo A, Tomasoni L, Castelli F, Sciandra M, Sinicco A, Ensoli F, Butto S, Ensoli B. The presence of anti-Tat antibodies is predictive of long-term nonprogression to AIDS or severe immunodeficiency: findings in a cohort of HIV-1 seroconverters. J Infect Dis. 2005 Apr 15;191(8):1321-4. doi: 10.1086/428909. Epub 2005 Mar 14.
PubMed 15776379Cafaro A, Caputo A, Fracasso C, Maggiorella MT, Goletti D, Baroncelli S, Pace M, Sernicola L, Koanga-Mogtomo ML, Betti M, Borsetti A, Belli R, Akerblom L, Corrias F, Butto S, Heeney J, Verani P, Titti F, Ensoli B. Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine. Nat Med. 1999 Jun;5(6):643-50. doi: 10.1038/9488.
PubMed 10371502Cafaro A, Caputo A, Maggiorella MT, Baroncelli S, Fracasso C, Pace M, Borsetti A, Sernicola L, Negri DR, Ten Haaft P, Betti M, Michelini Z, Macchia I, Fanales-Belasio E, Belli R, Corrias F, Butto S, Verani P, Titti F, Ensoli B. SHIV89.6P pathogenicity in cynomolgus monkeys and control of viral replication and disease onset by human immunodeficiency virus type 1 Tat vaccine. J Med Primatol. 2000 Aug;29(3-4):193-208. doi: 10.1034/j.1600-0684.2000.290313.x.
PubMed 11085582Butto S, Fiorelli V, Tripiciano A, Ruiz-Alvarez MJ, Scoglio A, Ensoli F, Ciccozzi M, Collacchi B, Sabbatucci M, Cafaro A, Guzman CA, Borsetti A, Caputo A, Vardas E, Colvin M, Lukwiya M, Rezza G, Ensoli B; Tat Multicentric Study Group. Sequence conservation and antibody cross-recognition of clade B human immunodeficiency virus (HIV) type 1 Tat protein in HIV-1-infected Italians, Ugandans, and South Africans. J Infect Dis. 2003 Oct 15;188(8):1171-80. doi: 10.1086/378412. Epub 2003 Sep 30.
PubMed 14551888
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Safety and Immunogenicity Trial of Recombinant HIV-1 Tat in HIV-1 Infected Adult Volunteers
- ClinicalTrials.gov ID
- NCT00505401
- Acronym / sponsor ID
- ISST-001 / ISST-001
- Conditions
- HIV Infections
- Keywords
- HIV, Tat protein, HIV Therapeutic Vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Istituto Superiore di SanitàUniversity, hospital or other
- Study start
- Dec 2003
- Study completion
- Nov 2007 (actual)
- First posted
- 23 Jul 2007 (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.
The development of a vaccine against HIV/AIDS has been primary focused on the structural proteins (Env, Gag) of HIV-1 with the aim of inducing sterilizing immunity by blocking virus entry. Alternative approaches are focused on new vaccine strategies aimed at modifying the virus-host dynamic favouring the establishment of a long-term non-progressing disease status. Such strategies target regulatory proteins that are the first to be expressed after infection and are essential for viral replication, infectivity and pathogenesis. Thus, this approach may be effective for both preventive and therapeutic vaccination strategies.
Detailed description
Being a very early viral regulatory protein necessary for viral gene expression, cell-to-cell virus transmission and disease progression, Tat represents a key target protein for the host immune response and an optimal candidate for such a vaccination strategy.
Preclinical studies demonstrated that vaccination with a biologically active Tat protein is safe, elicits a broad and specific immune response and induces a long-term protection against infection. Cross-sectional and longitudinal studies in natural infection suggest that the presence of an anti-Tat humoral immune response correlates with asymptomatic infection and with a slower disease progression while the presence of CD8+ T cell responses to Tat correlate with early virus control both in humans and monkeys. Since the immunogenic regions of Tat are well conserved among the HIV-1 M group, a vaccine based on Tat may be used in different geographic areas of the world.
This Phase I study was directed at evaluating the safety profile (as a primary end-point) and the immunogenicity (as a secondary end-point) of the recombinant HIV-1 Tat vaccine in HIV-1 infected adult volunteers with mild immune deficiency (Clinical category A according to CDC), CD4+ T cell counts 400/mL and levels of plasma viremia < 50,000 copies/mL.
Study Design: Randomized, Double Blind, Placebo Controlled, Safety/Immunogenicity Study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Other | Biological: recombinant HIV-1 Tat proteinSubjects were immunized subcutaneously with Tat, 3 dosage groups (7.5, 15 or 30 microgrammi), in association with Alum as adjuvant, or with Saline + Alum, as placebo. |
| B | Other | Biological: recombinant HIV-1 Tat proteinSubjects were immunized intradermally with Tat, 3 dosage groups (7.5, 15 or 30 microgrammi), or with Saline, as placebo. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- Negative pregnancy test for women of childbearing potential within 3 days prior to baseline evaluation and use of an acceptable means of contraception (condom, hormonal or mechanical method) for one month prior to immunization and the duration of the study;
- Clinically asymptomatic HIV-1 infected individuals (CDC Clinical category A), as determined by two positive Enzyme-linked immunosorbent assay (ELISA) and a confirmatory Western Blot;
- Mean CD4+ T cell count >= 400 cells/microL based on 2 separate determinations, at least 2 weeks apart, within the four weeks pre-study screening period. [Note: If one of the two values is < 400 the patient will be excluded. Patients ever having had a value of CD4+ T cell number < 250 will be excluded];
- Plasma HIV-1 viremia levels <= 50,000 copies/mL;
- Complete blood count and differential defined as:
Key exclusion criteria (20 listed)
- History of AIDS-related opportunistic or neoplastic disease;
- History of encephalopathy, neuropathy, or unstable CNS pathology (HIV or non-HIV related);
- History of non-HIV related neoplastic diseases, autoimmune diseases, angina or cardiac arthymias, or any other clinically significant medical problems;
- Chest radiography showing evidence of active or acute cardiac or pulmonary disease;
- History of anaphylaxis or serious adverse reactions to vaccines as well as serum IgE levels exceeding 1000 U.I./mL;
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 |
|---|---|---|
| recombinant HIV-1 Tat protein | Biological | A, B |
Primary outcome
Assessment of product safety included clinical monitoring of volunteers for local and systemic adverse reactions during the course of the trial and monitoring of haematological, biochemical, virological and immunological parameters
1 secondary outcome
To qualify Tat protein as immunogenic, volunteers were monitored for anti-Tat specific antibodies (IgM, IgG, IgA), anti-Tat proliferative response and in vitro γIFN and IL-4 production by PBMC before vaccination and in response to Tat vaccine.
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 1 Mar 2011.
- Background: PubMed 17117011Ensoli B, Fiorelli V, Ensoli F, Cafaro A, Titti F, Butto S, Monini P, Magnani M, Caputo A, Garaci E. Candidate HIV-1 Tat vaccine development: from basic science to clinical trials. AIDS. 2006 Nov 28;20(18):2245-61. doi: 10.1097/QAD.0b013e3280112cd1. No abstract available.
- Background: PubMed 15776379Rezza G, Fiorelli V, Dorrucci M, Ciccozzi M, Tripiciano A, Scoglio A, Collacchi B, Ruiz-Alvarez M, Giannetto C, Caputo A, Tomasoni L, Castelli F, Sciandra M, Sinicco A, Ensoli F, Butto S, Ensoli B. The presence of anti-Tat antibodies is predictive of long-term nonprogression to AIDS or severe immunodeficiency: findings in a cohort of HIV-1 seroconverters. J Infect Dis. 2005 Apr 15;191(8):1321-4. doi: 10.1086/428909. Epub 2005 Mar 14.
- Background: PubMed 10371502Cafaro A, Caputo A, Fracasso C, Maggiorella MT, Goletti D, Baroncelli S, Pace M, Sernicola L, Koanga-Mogtomo ML, Betti M, Borsetti A, Belli R, Akerblom L, Corrias F, Butto S, Heeney J, Verani P, Titti F, Ensoli B. Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine. Nat Med. 1999 Jun;5(6):643-50. doi: 10.1038/9488.
- Background: PubMed 11085582Cafaro A, Caputo A, Maggiorella MT, Baroncelli S, Fracasso C, Pace M, Borsetti A, Sernicola L, Negri DR, Ten Haaft P, Betti M, Michelini Z, Macchia I, Fanales-Belasio E, Belli R, Corrias F, Butto S, Verani P, Titti F, Ensoli B. SHIV89.6P pathogenicity in cynomolgus monkeys and control of viral replication and disease onset by human immunodeficiency virus type 1 Tat vaccine. J Med Primatol. 2000 Aug;29(3-4):193-208. doi: 10.1034/j.1600-0684.2000.290313.x.
- Background: PubMed 14551888Butto S, Fiorelli V, Tripiciano A, Ruiz-Alvarez MJ, Scoglio A, Ensoli F, Ciccozzi M, Collacchi B, Sabbatucci M, Cafaro A, Guzman CA, Borsetti A, Caputo A, Vardas E, Colvin M, Lukwiya M, Rezza G, Ensoli B; Tat Multicentric Study Group. Sequence conservation and antibody cross-recognition of clade B human immunodeficiency virus (HIV) type 1 Tat protein in HIV-1-infected Italians, Ugandans, and South Africans. J Infect Dis. 2003 Oct 15;188(8):1171-80. doi: 10.1086/378412. Epub 2003 Sep 30.
- Related InfoLink 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.
Barbara Ensoli, MD, PhD study director
National AIDS Center, Istituto Superiore di Sanità, Rome, Italy
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing recombinant HIV-1 Tat protein in people with HIV Infections, run by Istituto Superiore di Sanità at 4 sites in Italy.
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 16 inclusion and 20 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 1 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
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?
Assessment of product safety included clinical monitoring of volunteers for local and systemic adverse reactions during the course of the trial and monitoring of haematological, biochemical, virological and immunological parameters. 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 NCT00505401, which also lists 5 linked publications.
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 1 Mar 2011.