HIV InfectionsPhase 1TL01NCT01285141
Reactogenicity and Immunogenicity of Cervico-vaginal CN54gp140-hsp70 Conjugate Vaccine
A Phase 1 study testing CN54gp140 glycoprotein-hsp70 conjugate vaccine in people with HIV Infections, run by St George's, University of London at 1 site in United Kingdom.
Trial summary
A vaccine to prevent infection with the Human Immunodeficiency Virus (HIV) is urgently needed. Worldwide, most HIV infections occur through sex between a man and woman. The vaccine in this study consists of a protein from HIV that has been synthetically produced and linked to a protein that boosts immune responses. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- CN54gp140 glycoprotein-hsp70 conjugate vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jul 2011to Dec 2012
- 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 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adult female volunteers, 18 to 45 years of age, who have signed an informed consent form following a detailed written explanation of participation in the protocol.
- Volunteers who are in good health as determined by medical history, physical examination and clinical judgement.
- Available for the duration of the study.
- Women who, if capable of becoming pregnant during the study, have agreed to have a pregnancy test immediately before immunisation, and to use appropriate contraception methods during the whole study period. Appropriate contraception shall include physician-prescribed oral hormonal agents, barrier contraceptives, regular and consistent use of condoms without spermicidal agents, or intrauterine devices only.
- Agree not to undertake any vaginal practices other than receptive intercourse with a male or use of sanitary tampons during menses. Use of condoms without spermicidal agents is encouraged.
- Have not donated blood during 3 months prior to study entry and agree to not donate for 3 months after the end of their participation in the study
Who cannot join
- They have hypersensitivity to any component of the vaccine used in this study.
- They are found to be HIV antibody or HIV proviral DNA positive at the time of initial screening.
- They have a known or suspected history of cervico-vaginal disease, malignancy or abnormality discovered at time of screening, or who have undergone a Letts procedure.
- They present in the samples obtained at the screening visit:
- a clinically significant abnormality in the haematological or biochemical assays.
- Positive tests for Hepatitis B and/or C infection
Show all 17Show fewer
- Positive tests for genital infections: Chlamydia trachomatis, Neisseria gonorrhoea, Treponema pallidum (syphilis).
- An abnormal value will be defined by the ranges quoted by pathology laboratory.
- They have a known or suspected impairment of lung, heart, liver, kidney, blood disorders or immune dysfunction.
- They are receiving immunosuppressive therapy (including systemic steroids).
- They are receiving any regular medications via vaginal route.
- They have any acute infections (including fever greater than or equal to 38°C) or any chronic disease.
- They present a current problem with substance abuse or with a history of substance abuse, which, in the opinion of the investigator, might interfere with participation in the study.
- They have any condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
- They have received an investigational agent within 3 months prior to study entry.
- They cannot speak fluent English
- They are planning to leave the area of the study site prior to the end of the study period, or are likely not to complete the study.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
St George's - University of London
London, England, SW17 0RE
About this study
Official title: Phase I Clinical Trial in Healthy Female Volunteers of Reactogenicity and Immunogenicity of Three Cervico-vaginal Topical Immunisations With a Fixed Dose of HIV CN54gp140 Glycoprotein-hsp70 Conjugate Vaccine
A vaccine to prevent infection with the Human Immunodeficiency Virus (HIV) is urgently needed. Worldwide, most HIV infections occur through sex between a man and woman. The vaccine in this study consists of a protein from HIV that has been synthetically produced and linked to a protein that boosts immune responses. It has not been tested in humans before, but it is expected (from animal studies) that direct application into the female genital tract (via the vagina) as liquid drops, will provoke immune protection at the site of HIV infection. This is less applicable to men, therefore only healthy, HIV negative women will be recruited. The investigators will recruit at one site, which is a university vaccine research centre with experience of running similar trials. The study will last 24 weeks during which subjects will have blood samples taken on six visits, and three immunisations over 12 weeks in which 1 millilitres of vaccine is placed into the vaginal by inserting a small plastic syringe. The purpose of this initial small study is to monitor safety of the vaccine and to determine whether it is appropriate to continue into future, larger studies in which the immune response to the vaccine is measured.
Read the detailed description
This hypothesis-generating, first-in-human, Phase 1 study will be conducted according to the Standard Operating Procedures (SOPs) of St George's. The purpose of the study is to determine the immediate safety and reactogenicity of the vaccine, to guide future larger Phase 1/2 studies of safety and efficacy.
Eight subjects will be included to receive 3 cervico-vaginal topical applications of 100µg of CN54gp140-hsp70 conjugate vaccine in 1.0 mL physiological buffer, administered as topical intra-vaginal drops on day 0, and at 4 and 12 weeks after the first immunisation. The study will consist of 1 pre-study screening visit, 3 immunisation visits, and 2 follow-up visits over a total period of 20 weeks. Subjects will be recruited as one cohort in two groups of four. The dose of antigens and immunisation schedule has been selected based on pre-clinical and clinical experience with the same HIV envelope protein.
Each subject's medical history (including past and present illnesses, current medications, family medical history) will be formally assessed and recorded at screening. Volunteers' age, gender, height, weight and ethnic origin will be recorded. A full physical examination will be conducted by a registered medical practitioner at screening and the final study visit. Regular assessments of vital signs (pulse, blood pressure, temperature) will be made on all visits.
Diary cards, investigator-prompted recall of events, laboratory tests (haematology, biochemistry) and direct visualisation of immunisation site will be used to identify Adverse Events. Frequency of vaccine-related Adverse Events is the Primary Study Endpoint.
Before and after each immunisation visit (0, 4 and 12 weeks) blood samples will be obtained for collection of serum and for separation of PBMCs for cellular assays. At each time point, vaginal and cervical secretions will be taken. All immunology assays are exploratory and are not study endpoints. HIV serology and DNA detection will be repeated at the final visit to detect subjects who may have contracted HIV infection during the study period, and who may therefore have developed antibody and T-cell responses due to the HIV infection that would interfere with exploratory immunology assays.
- Conditions
- HIV Infections
- Being tested
- CN54gp140 glycoprotein-hsp70 conjugate vaccine
- Keywords
- HIV Infections, Acquired Immune Deficiency Syndrome
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CN54gp140 glycoprotein-hsp70 conjugate vaccineBiological
Also called ZM96gp140 glycoprotein
CN54gp140-hsp70 conjugate vaccine administered intravaginally 3 times over a 12-week period
| Study group | Role | What they receive |
|---|---|---|
| Vaginal immunisation | Experimental | CN54gp140 glycoprotein-hsp70 conjugate vaccine Receives: Biological: CN54gp140 glycoprotein-hsp70 conjugate vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of local immunisation site vaccine-related Adverse Events
Semi-structured diary card of solicited local symptoms (vaginal irritation, discharge, bleeding), investigator-prompted recall of unsolicited symptoms, recorded for 20 weeks from day of first immunisation. Visual inspection of cervix-vagina by trained operator prior to immunisation and on final visit.
Measured: 20 weeks
Secondary outcomes (7)
Frequency of generalised vaccine-related Adverse Events
Semi-structured diary card of solicited generalised symptoms (headache, fever, malaise, chills, myalgia), investigator-prompted recall of unsolicited symptoms, recorded for 20 weeks from day of first immunisation.
Measured: 20
Frequency of vaccine-related Adverse Events in hematology and serum biochemistry parameters
Adverse Events defined as deviation from normal ranges defined for pre-determined panels of hematology and serum biochemistry parameters.
Measured: 20
Frequency of subjects mounting a cervico-vaginal antibody response to CN54gp140
Exploratory assay of cervico-vaginal antibody to CN54gp140, measured at each scheduled study visit. Not a study endpoint.
Measured: 20 weeks
Frequency of subjects mounting a cervico-vaginal antibody response to hsp70
Exploratory assay of cervico-vaginal antibody to hsp70, measured at each scheduled study visit. Not a study endpoint.
Measured: 20 weeks
Frequency of subjects mounting a T cellular proliferative response to CN54gp140
Exploratory assay of T cell proliferation in response to in vitro antigen stimulation, measured at each scheduled study visit. Not a study endpoint.
Measured: 20 weeks
Frequency of subjects mounting a serum antibody response to CN54gp140
Exploratory assay of serum antibody to CN54gp140, measured at each scheduled study visit. Not a study endpoint.
Measured: 20 weeks
Frequency of subjects mounting a serum antibody response to hsp70
Exploratory assay of serum antibody to hsp70, measured at each scheduled study visit. Not a study endpoint.
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2011 (estimated)
- Study startJul 2011
- Primary completionJan 2012
- Study completionDec 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 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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- St George's, University of London
- Sponsor type
- University, hospital or other
- Collaborators
- European Union
- Responsible party
- Principal investigator, David JM Lewis, St George's, University of London
- Investigators
- David JM Lewis, MD, Principal investigator, St George's, University of London, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01285141
- Sponsor's protocol ID
- 2010-022740-20
- Acronym
- TL01
- Status last verified
- Dec 2012
- First submitted
- 26 Jan 2011
- Last updated
- 5 Dec 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Lewis DJ, Wang Y, Huo Z, Giemza R, Babaahmady K, Rahman D, Shattock RJ, Singh M, Lehner T. Effect of vaginal immunization with HIVgp140 and HSP70 on HIV-1 replication and innate and T cell adaptive immunity in women. J Virol. 2014 Oct;88(20):11648-57. doi: 10.1128/JVI.01621-14. Epub 2014 Jul 9.
PubMed 25008917
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial in Healthy Female Volunteers of Reactogenicity and Immunogenicity of Three Cervico-vaginal Topical Immunisations With a Fixed Dose of HIV CN54gp140 Glycoprotein-hsp70 Conjugate Vaccine
- ClinicalTrials.gov ID
- NCT01285141
- Acronym / sponsor ID
- TL01 / 2010-022740-20
- Conditions
- HIV Infections
- Keywords
- HIV Infections, Acquired Immune Deficiency Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- St George's, University of LondonUniversity, hospital or other
- Collaborators
- European Union
- Study start
- Jul 2011
- Primary completion
- Jan 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 27 Jan 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.
A vaccine to prevent infection with the Human Immunodeficiency Virus (HIV) is urgently needed. Worldwide, most HIV infections occur through sex between a man and woman. The vaccine in this study consists of a protein from HIV that has been synthetically produced and linked to a protein that boosts immune responses. It has not been tested in humans before, but it is expected (from animal studies) that direct application into the female genital tract (via the vagina) as liquid drops, will provoke immune protection at the site of HIV infection. This is less applicable to men, therefore only healthy, HIV negative women will be recruited. The investigators will recruit at one site, which is a university vaccine research centre with experience of running similar trials. The study will last 24 weeks during which subjects will have blood samples taken on six visits, and three immunisations over 12 weeks in which 1 millilitres of vaccine is placed into the vaginal by inserting a small plastic syringe. The purpose of this initial small study is to monitor safety of the vaccine and to determine whether it is appropriate to continue into future, larger studies in which the immune response to the vaccine is measured.
Detailed description
This hypothesis-generating, first-in-human, Phase 1 study will be conducted according to the Standard Operating Procedures (SOPs) of St George's. The purpose of the study is to determine the immediate safety and reactogenicity of the vaccine, to guide future larger Phase 1/2 studies of safety and efficacy.
Eight subjects will be included to receive 3 cervico-vaginal topical applications of 100µg of CN54gp140-hsp70 conjugate vaccine in 1.0 mL physiological buffer, administered as topical intra-vaginal drops on day 0, and at 4 and 12 weeks after the first immunisation. The study will consist of 1 pre-study screening visit, 3 immunisation visits, and 2 follow-up visits over a total period of 20 weeks. Subjects will be recruited as one cohort in two groups of four. The dose of antigens and immunisation schedule has been selected based on pre-clinical and clinical experience with the same HIV envelope protein.
Each subject's medical history (including past and present illnesses, current medications, family medical history) will be formally assessed and recorded at screening. Volunteers' age, gender, height, weight and ethnic origin will be recorded. A full physical examination will be conducted by a registered medical practitioner at screening and the final study visit. Regular assessments of vital signs (pulse, blood pressure, temperature) will be made on all visits.
Diary cards, investigator-prompted recall of events, laboratory tests (haematology, biochemistry) and direct visualisation of immunisation site will be used to identify Adverse Events. Frequency of vaccine-related Adverse Events is the Primary Study Endpoint.
Before and after each immunisation visit (0, 4 and 12 weeks) blood samples will be obtained for collection of serum and for separation of PBMCs for cellular assays. At each time point, vaginal and cervical secretions will be taken. All immunology assays are exploratory and are not study endpoints. HIV serology and DNA detection will be repeated at the final visit to detect subjects who may have contracted HIV infection during the study period, and who may therefore have developed antibody and T-cell responses due to the HIV infection that would interfere with exploratory immunology assays.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vaginal immunisation | Experimental | Biological: CN54gp140 glycoprotein-hsp70 conjugate vaccineCN54gp140 glycoprotein-hsp70 conjugate vaccine |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Adult female volunteers, 18 to 45 years of age, who have signed an informed consent form following a detailed written explanation of participation in the protocol.
- Volunteers who are in good health as determined by medical history, physical examination and clinical judgement.
- Available for the duration of the study.
- Women who, if capable of becoming pregnant during the study, have agreed to have a pregnancy test immediately before immunisation, and to use appropriate contraception methods during the whole study period. Appropriate contraception shall include physician-prescribed oral hormonal agents, barrier contraceptives, regular and consistent use of condoms without spermicidal agents, or intrauterine devices only.
- Agree not to undertake any vaginal practices other than receptive intercourse with a male or use of sanitary tampons during menses. Use of condoms without spermicidal agents is encouraged.
Key exclusion criteria (17 listed)
- They have hypersensitivity to any component of the vaccine used in this study.
- They are found to be HIV antibody or HIV proviral DNA positive at the time of initial screening.
- They have a known or suspected history of cervico-vaginal disease, malignancy or abnormality discovered at time of screening, or who have undergone a Letts procedure.
- They present in the samples obtained at the screening visit:
- a clinically significant abnormality in the haematological or biochemical assays.
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 |
|---|---|---|
| CN54gp140 glycoprotein-hsp70 conjugate vaccineAlso: ZM96gp140 glycoproteinCN54gp140-hsp70 conjugate vaccine administered intravaginally 3 times over a 12-week period | Biological | Vaginal immunisation |
Primary outcome
Frequency of local immunisation site vaccine-related Adverse Events
Time frame: 20 weeks
Semi-structured diary card of solicited local symptoms (vaginal irritation, discharge, bleeding), investigator-prompted recall of unsolicited symptoms, recorded for 20 weeks from day of first immunisation. Visual inspection of cervix-vagina by trained operator prior to immunisation and on final visit.
7 secondary outcomes
Frequency of generalised vaccine-related Adverse Events
Time frame: 20
Frequency of vaccine-related Adverse Events in hematology and serum biochemistry parameters
Time frame: 20
Frequency of subjects mounting a cervico-vaginal antibody response to CN54gp140
Time frame: 20 weeks
Frequency of subjects mounting a cervico-vaginal antibody response to hsp70
Time frame: 20 weeks
Frequency of subjects mounting a T cellular proliferative response to CN54gp140
Time frame: 20 weeks
Frequency of subjects mounting a serum antibody response to CN54gp140
Time frame: 20 weeks
Frequency of subjects mounting a serum antibody response to hsp70
Time frame: 20 weeks
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 5 Dec 2012.
- Derived from this study: PubMed 25008917Lewis DJ, Wang Y, Huo Z, Giemza R, Babaahmady K, Rahman D, Shattock RJ, Singh M, Lehner T. Effect of vaginal immunization with HIVgp140 and HSP70 on HIV-1 replication and innate and T cell adaptive immunity in women. J Virol. 2014 Oct;88(20):11648-57. doi: 10.1128/JVI.01621-14. Epub 2014 Jul 9.
- St George's, University of LondonLink 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.
David JM Lewis, MD principal investigator
St George's, University of London, UK
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 CN54gp140 glycoprotein-hsp70 conjugate vaccine in people with HIV Infections, run by St George's, University of 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 6 inclusion and 17 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 5 Dec 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 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 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?
Frequency of local immunisation site vaccine-related Adverse Events (time frame: 20 weeks). 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 NCT01285141, 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 5 Dec 2012.