HIV-1 InfectionPhase 1IMIRC1003NCT01130376
Novel Interventions in HIV-1 Infection
A Phase 1 study testing GTU-MultiHIV B clade vaccine1mg, Interleukin-2 and GM-CSF in people with HIV-1 Infection, run by Imperial College London at 1 site in United Kingdom.
Trial summary
For several years there has been interest in why some people with HIV-1 progress more slowly to disease and have longer survival without Highly Active Antiretroviral Therapy (HAART) than others. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- GTU-MultiHIV B clade vaccine1mg, Interleukin-2 and GM-CSF
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2009to Oct 2011
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented HIV-1 positive result.
- Stable on HAART.
- Two screening viral loads of <50 cps/ml on 2 consecutive occasions at least one month apart.
- CD4 T cell count of >400 cells/ul.
- Nadir CD4 T cell count of >200 cells/ul.
- Over 18 years of age.
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- Willing and able to provide informed consent.
- Female subjects must not be pregnant or lactating.
- Subjects must be using adequate double barrier method of contraception as appropriate.
Who cannot join
- Prior therapeutic vaccination.
- Acute illness within 2 weeks of the start of the study.
- Prior immunomodulatory therapy (e.g. IL-2, rhGH, GCSF, GM-CSF, HU)
- Receiving immunosuppressive medication (e.g. Steroids)
- Participation in other vaccine trials currently
- Patients with diabetes mellitus type 2
Show all 10Show fewer
- Patients with cardiac abnormalities
- Patients with pre-existing autoimmune disease
- Patients with active neoplasia
- Patients with evidence of any progression or recurrence of an underlying intra-cranial lesion
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, Open Labelled, Phase I, Safety, Toxicity, and Exploratory Immunogenicity Evaluation of Therapeutic Immunisation +/- IL-2, GM-CSF and Growth Hormone in HIV-1 Infected Subjects Receiving Highly Active Anti-retroviral Therapy
For several years there has been interest in why some people with HIV-1 progress more slowly to disease and have longer survival without Highly Active Antiretroviral Therapy (HAART) than others. The investigators and others have identified a few HIV positive individuals who can control their viral load for many years without HAART, these rare individuals do not lose their HIV-1-specific cellular immune responses, which are very important for controlling viral load. This group is referred to as long-term non-progressors (LTNP). Unlike LTNP the majority of HIV-1 infected individuals are chronic progressors (CP) who do not make effective HIV-1-specific cellular immune responses, even when on HAART. We propose to use a novel DNA vaccine boosted with immune based therapy (cytokines and hormones) to try to regenerate the missing HIV-1-specific cellular immune responses to make chronically infected HIV-1+ persons more like LTNP.
By injecting this novel DNA vaccine and immune based therapy into the people who are already infected with HIV-1, the immune system may be stimulated to mount a greater immune response not only to the vaccines but also to real HIV-1 particles and HIV-1-infected cells.
Read the detailed description
This will be a randomised, Phase I, open label comparative study running for 52 weeks (2 screen visits 2 weeks apart followed by 48 weeks of study). 50 patients will be screened in the initial phase of which 30 clade B infected individuals will be randomised into the study, which will consist of 3 arms:
Arm 1 will ascertain vaccine safety and toxicity in the presence of cytokine/hormone therapy.
Arm 2 will identify vaccine safety and toxicity.
Arm 3 will indicate safety and toxicity of cytokine/hormone therapy.
The target patients are chronically HIV-1 clade B infected persons who will have had a nadir CD4 T-cell count of >200 cells/ul blood before they started ART. The current CD4 T-cell count should be >400 cells/ul blood. Patients may have received ART for any length of time, but currently should be receiving NNRTI or boosted-PI based HAART, and have a viral load below the level of detection (50 copies/ml plasma). Patients will be bled on two occasions before commencing IBT regimens, in order to establish baselines, and then at regular intervals thereafter (weeks 0,1,2,4,6,8,12,16,24 and 48).
The treatment regimens are consistent with previous findings in animal models which suggest that administration of IL-2 during the antigen-specific T-cell contraction phase of an immune response (between 8 and 15 days post-vaccination) may preserve and lengthen clinically relevant responses. Furthermore studies in man have demonstrated that IL-2 administered before immunisation in ART-treated HIV-1-infected patients does not increase specific lymphoproliferation of T cells.
Recent preliminary studies in HIV-1-infected individuals using tetanus vaccines the investigators have shown that IL-2 administered after immunisation may be more effective at inducing sustained tetanus-specific responses than IL-2 administered before immunisation or together with immunisation. The dosages used in this study are based on those used in previous pilot studies of the administration of IL-2 + GM-CSF and rhGH and at these levels the drugs have been shown to have both positive effect on the immune response and demonstrated clinical benefit whilst being at a level which is safe and well tolerated in HIV-1 positive individuals. The dosage of the vaccine was based on a previous study where a dosage of this level has been shown to induce an immune response although this response was transient. In summary the investigators aim to increase the survival of vaccine responses through the administration of cytokines/hormones and boost memory responses with further rounds of immunisation.
- Conditions
- HIV-1 Infection
- Being tested
- GTU-MultiHIV B clade vaccine1mg, Interleukin-2, GM-CSF, Growth Hormone
- Keywords
- Immune based therapy, Therapeutic vaccination, cytokine therapy, HIV therapeutic vaccine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GTU-MultiHIV B clade vaccine1mgBiological
Dose given is 1mg/ml administered as 10 intradermal injections of 100 µl/injection distributed as 5 intradermal injections /left and right arm
Interleukin-2Drug
Also called Aldesleukin, Proleukin
5 Million Units administered twice daily for 5 days by subcutaneous injection on days 7, 8, 9, 10, and 11 after first vaccination. .
GM-CSFDrug
Also called Sargramostim, Leukine
150 ug administered subcutaneously once daily 4 hours from IL-2 injections
Growth HormoneDrug
Also called Serono International, Geneva, Switzerland
4mg/day will be self administered by Subcutaneous injection for 5 days on days 14, 15, 16, 17 and 18 following first vaccination
| Study group | Role | What they receive |
|---|---|---|
| Vaccine and cytokines | Experimental | Day 0: Patients receive GTU-MultiHIV B clade vaccine 1mg/ml administered as 10 intradermal injections of 100 µl/injection.
Day 7-11: One week following this, patients receive a 5 day course of Cytokines: Aldesleukin (IL-2) Novartis UK (BD; 8 hours apart) 5 million units administered by SC injection. Sargramostim (GM-CSF) - Leukine™, Berlex Seattle US 150ug SC once daily 4 hours from rhIL-2 injections.
Day 14-18: The following week, patients rhGH (Saizen™, Serono International, Geneva, Switzerland) 4mg/day self-administered SC.
Further vaccine boosters are given on day 42 and day 84. GTU-MultiHIV B clade vaccine 1mg/ml being administered as 10 intradermal injections of 100 µl/injection. Receives: Biological: GTU-MultiHIV B clade vaccine1mg; Drug: Interleukin-2; Drug: GM-CSF; Drug: Growth Hormone |
| Vaccine alone | Active comparator | Day 0: Patients are given GTU-MultiHIV B clade vaccine 1mg/ml administered as 10 intradermal injections of 100 µl/injections.
Day 42: GTU-MultiHIV B clade vaccine as day 0.
Day 84: GTU-MultiHIV B clade vaccine as day 0. Receives: Biological: GTU-MultiHIV B clade vaccine1mg |
| Cytokines alone | Active comparator | Day 7-11: One week following this, patients receive a 5 day course of Cytokines: Aldesleukin (IL-2) Novartis UK (BD; 8 hours apart) 5 million units administered by SC injection. Sargramostim (GM-CSF) - Leukine™, Berlex Seattle US 150ug SC once daily 4 hours from rhIL-2 injections.
Day 14-18: The following week, patients rhGH (Saizen™, Serono International, Geneva, Switzerland) 4mg/day self-administered SC. Receives: Drug: Interleukin-2; Drug: GM-CSF; Drug: Growth Hormone |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome will be analysis of safety and toxicity data in relation to grade 3 or above laboratory or clinical serious adverse event (SAE) which can be attributed to the treatments given
Measured: Weekly
Secondary outcomes (1)
The secondary immunological outcomes will be percentage change from baseline to study time point in defined cellular immune responses.
Measured: weekly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2010 (estimated)
- Study startSep 2009
- Primary completionOct 2011
- Study completionOct 2011
Why it stopped: Data from the 12 patients recruited has now been analysed, and it has been determined that it is sufficient to meet the study objectives.
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-1 InfectionStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council
- Responsible party
- Sponsor
- Investigators
- Nesrina Imami, MD/PhD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01130376
- Sponsor's protocol ID
- CRO930
- Other IDs
- G0501957, 2008-000575024, 2008
- Acronym
- IMIRC1003
- Status last verified
- Sep 2012
- First submitted
- 25 May 2010
- Last updated
- 4 Sep 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Herasimtschuk A, Downey J, Nelson M, Moyle G, Mandalia S, Sikut R, Adojaan M, Stanescu I, Gotch F, Imami N. Therapeutic immunisation plus cytokine and hormone therapy improves CD4 T-cell counts, restores anti-HIV-1 responses and reduces immune activation in treated chronic HIV-1 infection. Vaccine. 2014 Dec 5;32(51):7005-7013. doi: 10.1016/j.vaccine.2014.09.072. Epub 2014 Oct 22.
PubMed 25454870
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Open Labelled, Phase I, Safety, Toxicity, and Exploratory Immunogenicity Evaluation of Therapeutic Immunisation +/- IL-2, GM-CSF and Growth Hormone in HIV-1 Infected Subjects Receiving Highly Active Anti-retroviral Therapy
- ClinicalTrials.gov ID
- NCT01130376
- Acronym / sponsor ID
- IMIRC1003 / CRO930
- Conditions
- HIV-1 Infection
- Keywords
- Immune based therapy, Therapeutic vaccination, cytokine therapy, HIV therapeutic vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Data from the 12 patients recruited has now been analysed, and it has been determined that it is sufficient to meet the study objectives.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Medical Research Council
- Study start
- Sep 2009
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 26 May 2010 (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.
For several years there has been interest in why some people with HIV-1 progress more slowly to disease and have longer survival without Highly Active Antiretroviral Therapy (HAART) than others. The investigators and others have identified a few HIV positive individuals who can control their viral load for many years without HAART, these rare individuals do not lose their HIV-1-specific cellular immune responses, which are very important for controlling viral load. This group is referred to as long-term non-progressors (LTNP). Unlike LTNP the majority of HIV-1 infected individuals are chronic progressors (CP) who do not make effective HIV-1-specific cellular immune responses, even when on HAART. We propose to use a novel DNA vaccine boosted with immune based therapy (cytokines and hormones) to try to regenerate the missing HIV-1-specific cellular immune responses to make chronically infected HIV-1+ persons more like LTNP.
By injecting this novel DNA vaccine and immune based therapy into the people who are already infected with HIV-1, the immune system may be stimulated to mount a greater immune response not only to the vaccines but also to real HIV-1 particles and HIV-1-infected cells.
Detailed description
This will be a randomised, Phase I, open label comparative study running for 52 weeks (2 screen visits 2 weeks apart followed by 48 weeks of study). 50 patients will be screened in the initial phase of which 30 clade B infected individuals will be randomised into the study, which will consist of 3 arms:
Arm 1 will ascertain vaccine safety and toxicity in the presence of cytokine/hormone therapy.
Arm 2 will identify vaccine safety and toxicity.
Arm 3 will indicate safety and toxicity of cytokine/hormone therapy.
The target patients are chronically HIV-1 clade B infected persons who will have had a nadir CD4 T-cell count of >200 cells/ul blood before they started ART. The current CD4 T-cell count should be >400 cells/ul blood. Patients may have received ART for any length of time, but currently should be receiving NNRTI or boosted-PI based HAART, and have a viral load below the level of detection (50 copies/ml plasma). Patients will be bled on two occasions before commencing IBT regimens, in order to establish baselines, and then at regular intervals thereafter (weeks 0,1,2,4,6,8,12,16,24 and 48).
The treatment regimens are consistent with previous findings in animal models which suggest that administration of IL-2 during the antigen-specific T-cell contraction phase of an immune response (between 8 and 15 days post-vaccination) may preserve and lengthen clinically relevant responses. Furthermore studies in man have demonstrated that IL-2 administered before immunisation in ART-treated HIV-1-infected patients does not increase specific lymphoproliferation of T cells.
Recent preliminary studies in HIV-1-infected individuals using tetanus vaccines the investigators have shown that IL-2 administered after immunisation may be more effective at inducing sustained tetanus-specific responses than IL-2 administered before immunisation or together with immunisation. The dosages used in this study are based on those used in previous pilot studies of the administration of IL-2 + GM-CSF and rhGH and at these levels the drugs have been shown to have both positive effect on the immune response and demonstrated clinical benefit whilst being at a level which is safe and well tolerated in HIV-1 positive individuals. The dosage of the vaccine was based on a previous study where a dosage of this level has been shown to induce an immune response although this response was transient. In summary the investigators aim to increase the survival of vaccine responses through the administration of cytokines/hormones and boost memory responses with further rounds of immunisation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Vaccine and cytokines | Experimental | Biological: GTU-MultiHIV B clade vaccine1mg, Drug: Interleukin-2, Drug: GM-CSF, Drug: Growth HormoneDay 0: Patients receive GTU-MultiHIV B clade vaccine 1mg/ml administered as 10 intradermal injections of 100 µl/injection. Day 7-11: One week following this, patients receive a 5 day course of Cytokines: Aldesleukin (IL-2) Novartis UK (BD; 8 hours apart) 5 million units administered by SC injection. Sargramostim (GM-CSF) - Leukine™, Berlex Seattle US 150ug SC once daily 4 hours from rhIL-2 injections. Day 14-18: The following week, patients rhGH (Saizen™, Serono International, Geneva, Switzerland) 4mg/day self-administered SC. Further vaccine boosters are given on day 42 and day 84. GTU-MultiHIV B clade vaccine 1mg/ml being administered as 10 intradermal injections of 100 µl/injection. |
| Vaccine alone | Active comparator | Biological: GTU-MultiHIV B clade vaccine1mgDay 0: Patients are given GTU-MultiHIV B clade vaccine 1mg/ml administered as 10 intradermal injections of 100 µl/injections. Day 42: GTU-MultiHIV B clade vaccine as day 0. Day 84: GTU-MultiHIV B clade vaccine as day 0. |
| Cytokines alone | Active comparator | Drug: Interleukin-2, Drug: GM-CSF, Drug: Growth HormoneDay 7-11: One week following this, patients receive a 5 day course of Cytokines: Aldesleukin (IL-2) Novartis UK (BD; 8 hours apart) 5 million units administered by SC injection. Sargramostim (GM-CSF) - Leukine™, Berlex Seattle US 150ug SC once daily 4 hours from rhIL-2 injections. Day 14-18: The following week, patients rhGH (Saizen™, Serono International, Geneva, Switzerland) 4mg/day self-administered SC. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Documented HIV-1 positive result.
- Stable on HAART.
- Two screening viral loads of <50 cps/ml on 2 consecutive occasions at least one month apart.
- CD4 T cell count of >400 cells/ul.
- Nadir CD4 T cell count of >200 cells/ul.
Key exclusion criteria (10 listed)
- Prior therapeutic vaccination.
- Acute illness within 2 weeks of the start of the study.
- Prior immunomodulatory therapy (e.g. IL-2, rhGH, GCSF, GM-CSF, HU)
- Receiving immunosuppressive medication (e.g. Steroids)
- Participation in other vaccine trials currently
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 |
|---|---|---|
| GTU-MultiHIV B clade vaccine1mgDose given is 1mg/ml administered as 10 intradermal injections of 100 µl/injection distributed as 5 intradermal injections /left and right arm | Biological | Vaccine alone, Vaccine and cytokines |
| Interleukin-2Also: Aldesleukin, Proleukin5 Million Units administered twice daily for 5 days by subcutaneous injection on days 7, 8, 9, 10, and 11 after first vaccination. . | Drug | Cytokines alone, Vaccine and cytokines |
| GM-CSFAlso: Sargramostim, Leukine150 ug administered subcutaneously once daily 4 hours from IL-2 injections | Drug | Cytokines alone, Vaccine and cytokines |
| Growth HormoneAlso: Serono International, Geneva, Switzerland4mg/day will be self administered by Subcutaneous injection for 5 days on days 14, 15, 16, 17 and 18 following first vaccination | Drug | Cytokines alone, Vaccine and cytokines |
Primary outcome
The primary outcome will be analysis of safety and toxicity data in relation to grade 3 or above laboratory or clinical serious adverse event (SAE) which can be attributed to the treatments given
Time frame: Weekly
1 secondary outcome
The secondary immunological outcomes will be percentage change from baseline to study time point in defined cellular immune responses.
Time frame: weekly
Results and safety
The study was stopped early (reason given: Data from the 12 patients recruited has now been analysed, and it has been determined that it is sufficient to meet the study objectives.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2013.
- Derived from this study: PubMed 25454870Herasimtschuk A, Downey J, Nelson M, Moyle G, Mandalia S, Sikut R, Adojaan M, Stanescu I, Gotch F, Imami N. Therapeutic immunisation plus cytokine and hormone therapy improves CD4 T-cell counts, restores anti-HIV-1 responses and reduces immune activation in treated chronic HIV-1 infection. Vaccine. 2014 Dec 5;32(51):7005-7013. doi: 10.1016/j.vaccine.2014.09.072. Epub 2014 Oct 22.
- research team web pageLink 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.
Nesrina Imami, MD/PhD principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GTU-MultiHIV B clade vaccine1mg, Interleukin-2 and GM-CSF in people with HIV-1 Infection, run by Imperial College London at 1 site in United Kingdom.
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 9 inclusion and 10 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: stopped early, as of the sponsor's last update on 4 Sep 2013. 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 United Kingdom. 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 was stopped early (reason given: Data from the 12 patients recruited has now been analysed, and it has been determined that it is sufficient to meet the study objectives.). Results are not available in the source record.
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?
The primary outcome will be analysis of safety and toxicity data in relation to grade 3 or above laboratory or clinical serious adverse event (SAE) which can be attributed to the treatments given (time frame: Weekly). 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 NCT01130376, 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 4 Sep 2013.