HIV-1 InfectionPhase 1/2NCT01627678
Immunotherapy With Vacc-C5 With Adjuvant GM-CSF or Alhydrogel in HIV-1-infected Subjects on ART
A Phase 1/2 study testing Vacc-C5/GM-CSF and Vacc-C5/Alhydrogel in people with HIV-1 Infection, run by Bionor Immuno AS at 1 site in Norway.
Trial summary
Background: Despite the introduction of highly effective antiretroviral therapy (ART) regimes, which control the HIV infection and results in increases in CD4 cell counts and an undetectable viral load, many patients suffer from increased morbidity. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- Vacc-C5/GM-CSF and Vacc-C5/Alhydrogel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteNorway
- Study dates
- Sep 2012to Nov 2013
- 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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age between18 years and 55 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. Single blips (up to 500 copies/mL) are allowed.
- Documented pre-study CD4 cell count ≥ 400x106/L for at least six months (if below at screening, a re-analysis is allowed).
- Nadir (lowest ever) CD4 cell count ≥ 200x106/L (nadir below 200x106/L requires two consecutive analyses).
- 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 viral hepatitis B or C or 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 subjects 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.
About this study
Official title: Immunotherapy of HIV-infected Patients An Open, Dose-escalating Assessment of Vacc-C5 With Either GM-CSF or Alhydrogel as Adjuvant in HIV-1-infected Subjects on Antiretroviral Therapy (ART)
Background:
Despite the introduction of highly effective antiretroviral therapy (ART) regimes, which control the HIV infection and results in increases in CD4 cell counts and an undetectable viral load, many patients suffer from increased morbidity. There is evidence that presence of antibodies against the C5 region of gp120 strongly correlates with slower disease progression, and that loss of antibody responses to this region are associated with progression.
Read more
Investigational product:
Vacc-C5 is a single heterodimeric peptide-based HIV therapeutic vaccine corresponding to the C5 region on gp120 and the external domain of gp41. The vaccine is intended to create a non-neutralizing antibody against C5 region.
Study objectives:
- To evaluate safety of the vaccination regimens
- To evaluate C5-specific humoral immune responses (antibodies), T cell responses, T cell activation markers and other immune markers.
Read the detailed description
Background:
Despite the introduction of highly effective antiretroviral therapy (ART) regimes, which control the HIV infection and results in increases in CD4 cell counts and an undetectable viral load, many patients suffer from increased morbidity. There is evidence that presence of antibodies against the C5 region of gp120 strongly correlates with slower disease progression, and that loss of antibody responses to this region are associated with progression.
Investigational product:
Vacc-C5 is a single heterodimeric peptide-based HIV therapeutic vaccine corresponding to the C5 region on gp120 and the external domain of gp41. The rationale behind the Vacc-C5 is the finding that long-term non-progressors (LTNP) subjects have more antibodies towards the C5 part of gp120 than HIV infected subjects with a more rapid disease progression.
The primary objective of Vacc-C5 immunotherapy is to induce a humoral immune response. The vaccine is intended to create a non-neutralizing antibody against the C5 region and to thereby mimic a natural process in HIV-infected long-term non-progressors (LTNP) subjects.
Use of adjuvant:
Peptide vaccines are poorly immunogenic by themselves. To induce measurable levels of T helper cell type 1 (Th1) or type 2 (Th2) immune responses against these peptides, an adjuvant is often required.
Two different adjuvants are to be used in this study:
- GM-CSF which facilitates dendritic cell maturation and migration to the lymph nodes for antigen presentation. The regimen when using this adjuvant is intradermal administration.
- Aluminum-containing adjuvants is well known. They have been administered to human beings and animals in millions of doses of vaccines. This type of vaccine is usually administered intramuscularly or subcutaneously. In this study intramuscular administration will be used.
Primary objective:
It is to evaluate the safety of Vacc-C5 at three different dose levels given intradermally with GM-CSF as adjuvant or given intramuscularly with Alhydrogel as adjuvant.
Secondary objectives:
- To evaluate C5-specific humoral immune responses (antibodies).
- To evaluate the C5-specific T cell responses by ELISPOT and T cell proliferation.
- To evaluate T cell activation markers (e.g. CD38, HLA-DR) and other immune markers.
Study design:
The study is an open, dose-escalating, single centre study in HIV-positive subjects on treatment (ART). Two different vaccine regimens will be tested:
- Arm A: Vacc-C5 with GM-CSF as adjuvant administered intradermally.
- Arm B: Vacc-C5 with Alhydrogel as adjuvant administered intramuscularly.
Three dose levels of Vacc-C5 (100, 300 and 900 microgram will be tested for each of the two vaccination regimen. A dose escalation design (3+3) will be used, and if no dose limiting toxicity (DLT) is detected 18 subjects will be included in each arm.
Subjects who have been HIV-positive and stable on ART for the last 6 months with CD4 cell counts ≥400x 10 6 /L and who meet the other inclusion and exclusion criteria will be eligible for the study. The duration of the study is 26 weeks plus a screening period of up to 12 weeks.
During the Treatment Period, all subjects will remain on their ART and receive three immunizations; at Weeks 1, 2 and 4, with Vacc C5 including either GM-CSF or Alhydrogel as adjuvant.
The study is sequential, meaning that the first three subjects in each arm receive the lowest dose (three subjects) 100 µg Vacc-C5. If no dose limiting toxicity has been detected after week 4 vaccination, three more subjects will be added and the next dose level will be started.
- Conditions
- HIV-1 Infection
- Being tested
- Vacc-C5/GM-CSF, Vacc-C5/Alhydrogel
- Keywords
- HIV-1, Vacc-C5
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vacc-C5/GM-CSFDrug
Also called Vacc-C5 = C5-peptide, GM-CSF = Leukine
Arm 1=Arm A: Vacc-C5 with GM-CSF as adjuvant administered intradermally.
Vacc-C5/AlhydrogelDrug
Also called Vacc-C5 = C5-pepide, Alhydrogel = Aluminum-containing adjuvant
Arm 2=Arm B: Vacc-C5 with Alhydrogel as adjuvant administered intramuscularly.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1= Arm A: Vacc-C5 /GM-CSF. | Experimental | Arm 1=Arm A: Vacc-C5 with GM-CSF as adjuvant administered intradermally. Receives: Drug: Vacc-C5/GM-CSF |
| Arm 2=Arm B: Vacc-C5/Alhydrogel | Experimental | Arm 2=Arm B: Vacc-C5 with Alhydrogel as adjuvant administered intramuscularly. Receives: Drug: Vacc-C5/Alhydrogel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety measured as change of AE records, clinical chemistry (incl. CD4, CD8, HIV-1 RNA)and hematology laboratory elevations
- AEs recorded at each scheduled and unscheduled visit.
- Concomitant medications recorded at each scheduled visit.
- Vital signs (heart rate, blood pressure) at screening, weeks 1, 4, 6, 12, 13, 15, 21, 22 and 26 (End of study).
- Weight at screening and weight at weeks 1, 12 and 26 (End of study).
- Clinical laboratory evaluations (clinical chemistry, hematology) at screening, weeks 1, 4, 6, 12, 15, 21 and 26 (End of study).
- Viral load (HIV-1 RNA) at screening, weeks 1, 6, 15 and 26 (End of study).
- Urine stix at weeks 1, 4, 6, 12, 15, 21 and 26 (End of study).
Measured: From screening and week 1 to weeks 2, 4, 6, 12, 13, 15, 21, 22 and 26
Secondary outcomes (1)
Change in Humoral and T cell responses
- Humoral immune response - C5 antibody level at screening, weeks 1, 4, 6, 12, 13, 15, 21, 22 and 26 (End of study).
- B cell antibody level at weeks 1, 6, 13 and 22.
- T cell response and activation markers (e.g. CD38, HLA-DR) and other immune markers at weeks 1, 6, 15and 26 (End of study).
Measured: From screening and week 1 to weeks 4, 6, 12, 13, 15, 21, 22 and 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2012 (estimated)
- Study startSep 2012
- Primary completionNov 2013
- Study completionNov 2013
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.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bionor Immuno AS
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vidar Wendel-Hansen, MD PhD, Study director, Bionor Pharma AS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01627678
- Sponsor's protocol ID
- CTN-BI-Vacc-C5-2011/1
- Other IDs
- 2012-000710-11
- Status last verified
- Jan 2014
- First submitted
- 21 Jun 2012
- Last updated
- 14 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Brekke K, Sommerfelt M, Okvist M, Dyrhol-Riise AM, Kvale D. The therapeutic HIV Env C5/gp41 vaccine candidate Vacc-C5 induces specific T cell regulation in a phase I/II clinical study. BMC Infect Dis. 2017 Mar 24;17(1):228. doi: 10.1186/s12879-017-2316-x.
PubMed 28340570
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunotherapy of HIV-infected Patients An Open, Dose-escalating Assessment of Vacc-C5 With Either GM-CSF or Alhydrogel as Adjuvant in HIV-1-infected Subjects on Antiretroviral Therapy (ART)
- ClinicalTrials.gov ID
- NCT01627678
- Acronym / sponsor ID
- CTN-BI-Vacc-C5-2011/1
- Conditions
- HIV-1 Infection
- Keywords
- HIV-1, Vacc-C5
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Bionor Immuno ASIndustry (pharma, biotech, devices)
- Study start
- Sep 2012
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 26 Jun 2012 (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.
Background:
Despite the introduction of highly effective antiretroviral therapy (ART) regimes, which control the HIV infection and results in increases in CD4 cell counts and an undetectable viral load, many patients suffer from increased morbidity. There is evidence that presence of antibodies against the C5 region of gp120 strongly correlates with slower disease progression, and that loss of antibody responses to this region are associated with progression.
Investigational product:
Vacc-C5 is a single heterodimeric peptide-based HIV therapeutic vaccine corresponding to the C5 region on gp120 and the external domain of gp41. The vaccine is intended to create a non-neutralizing antibody against C5 region.
Study objectives:
- To evaluate safety of the vaccination regimens
- To evaluate C5-specific humoral immune responses (antibodies), T cell responses, T cell activation markers and other immune markers.
Detailed description
Background:
Despite the introduction of highly effective antiretroviral therapy (ART) regimes, which control the HIV infection and results in increases in CD4 cell counts and an undetectable viral load, many patients suffer from increased morbidity. There is evidence that presence of antibodies against the C5 region of gp120 strongly correlates with slower disease progression, and that loss of antibody responses to this region are associated with progression.
Investigational product:
Vacc-C5 is a single heterodimeric peptide-based HIV therapeutic vaccine corresponding to the C5 region on gp120 and the external domain of gp41. The rationale behind the Vacc-C5 is the finding that long-term non-progressors (LTNP) subjects have more antibodies towards the C5 part of gp120 than HIV infected subjects with a more rapid disease progression.
The primary objective of Vacc-C5 immunotherapy is to induce a humoral immune response. The vaccine is intended to create a non-neutralizing antibody against the C5 region and to thereby mimic a natural process in HIV-infected long-term non-progressors (LTNP) subjects.
Use of adjuvant:
Peptide vaccines are poorly immunogenic by themselves. To induce measurable levels of T helper cell type 1 (Th1) or type 2 (Th2) immune responses against these peptides, an adjuvant is often required.
Two different adjuvants are to be used in this study:
- GM-CSF which facilitates dendritic cell maturation and migration to the lymph nodes for antigen presentation. The regimen when using this adjuvant is intradermal administration.
- Aluminum-containing adjuvants is well known. They have been administered to human beings and animals in millions of doses of vaccines. This type of vaccine is usually administered intramuscularly or subcutaneously. In this study intramuscular administration will be used.
Primary objective:
It is to evaluate the safety of Vacc-C5 at three different dose levels given intradermally with GM-CSF as adjuvant or given intramuscularly with Alhydrogel as adjuvant.
Secondary objectives:
- To evaluate C5-specific humoral immune responses (antibodies).
- To evaluate the C5-specific T cell responses by ELISPOT and T cell proliferation.
- To evaluate T cell activation markers (e.g. CD38, HLA-DR) and other immune markers.
Study design:
The study is an open, dose-escalating, single centre study in HIV-positive subjects on treatment (ART). Two different vaccine regimens will be tested:
- Arm A: Vacc-C5 with GM-CSF as adjuvant administered intradermally.
- Arm B: Vacc-C5 with Alhydrogel as adjuvant administered intramuscularly.
Three dose levels of Vacc-C5 (100, 300 and 900 microgram will be tested for each of the two vaccination regimen. A dose escalation design (3+3) will be used, and if no dose limiting toxicity (DLT) is detected 18 subjects will be included in each arm.
Subjects who have been HIV-positive and stable on ART for the last 6 months with CD4 cell counts ≥400x 10 6 /L and who meet the other inclusion and exclusion criteria will be eligible for the study. The duration of the study is 26 weeks plus a screening period of up to 12 weeks.
During the Treatment Period, all subjects will remain on their ART and receive three immunizations; at Weeks 1, 2 and 4, with Vacc C5 including either GM-CSF or Alhydrogel as adjuvant.
The study is sequential, meaning that the first three subjects in each arm receive the lowest dose (three subjects) 100 µg Vacc-C5. If no dose limiting toxicity has been detected after week 4 vaccination, three more subjects will be added and the next dose level will be started.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1= Arm A: Vacc-C5 /GM-CSF. | Experimental | Drug: Vacc-C5/GM-CSFArm 1=Arm A: Vacc-C5 with GM-CSF as adjuvant administered intradermally. |
| Arm 2=Arm B: Vacc-C5/Alhydrogel | Experimental | Drug: Vacc-C5/AlhydrogelArm 2=Arm B: Vacc-C5 with Alhydrogel as adjuvant administered intramuscularly. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Age between18 years and 55 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. Single blips (up to 500 copies/mL) are allowed.
- Documented pre-study CD4 cell count ≥ 400x106/L for at least six months (if below at screening, a re-analysis is allowed).
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 viral hepatitis B or C or 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-C5/GM-CSFAlso: Vacc-C5 = C5-peptide, GM-CSF = LeukineArm 1=Arm A: Vacc-C5 with GM-CSF as adjuvant administered intradermally. | Drug | Arm 1= Arm A: Vacc-C5 /GM-CSF. |
| Vacc-C5/AlhydrogelAlso: Vacc-C5 = C5-pepide, Alhydrogel = Aluminum-containing adjuvantArm 2=Arm B: Vacc-C5 with Alhydrogel as adjuvant administered intramuscularly. | Drug | Arm 2=Arm B: Vacc-C5/Alhydrogel |
Primary outcome
Safety measured as change of AE records, clinical chemistry (incl. CD4, CD8, HIV-1 RNA)and hematology laboratory elevations
Time frame: From screening and week 1 to weeks 2, 4, 6, 12, 13, 15, 21, 22 and 26
* AEs recorded at each scheduled and unscheduled visit. * Concomitant medications recorded at each scheduled visit. * Vital signs (heart rate, blood pressure) at screening, weeks 1, 4, 6, 12, 13, 15, 21, 22 and 26 (End of study). * Weight at screening and weight at weeks 1, 12 and 26 (End of study). * Clinical laboratory evaluations (clinical chemistry, hematology) at screening, weeks 1, 4, 6, 12, 15, 21 and 26 (End of study). * Viral load (HIV-1 RNA) at screening, weeks 1, 6, 15 and 26 (End of study). * Urine stix at weeks 1, 4, 6, 12, 15, 21 and 26 (End of study).
1 secondary outcome
Change in Humoral and T cell responses
Time frame: From screening and week 1 to weeks 4, 6, 12, 13, 15, 21, 22 and 26
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 14 Jan 2014.
- Derived from this study: PubMed 28340570Brekke K, Sommerfelt M, Okvist M, Dyrhol-Riise AM, Kvale D. The therapeutic HIV Env C5/gp41 vaccine candidate Vacc-C5 induces specific T cell regulation in a phase I/II clinical study. BMC Infect Dis. 2017 Mar 24;17(1):228. doi: 10.1186/s12879-017-2316-x.
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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.
Vidar Wendel-Hansen, MD PhD study director
Bionor Pharma AS
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-C5/GM-CSF and Vacc-C5/Alhydrogel in people with HIV-1 Infection, run by Bionor Immuno AS 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 14 Jan 2014. 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. 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?
Safety measured as change of AE records, clinical chemistry (incl. CD4, CD8, HIV-1 RNA)and hematology laboratory elevations (time frame: From screening and week 1 to weeks 2, 4, 6, 12, 13, 15, 21, 22 and 26). 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 NCT01627678, 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 14 Jan 2014.