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Reactogenicity and Immunogenicity of Cervico-vaginal CN54gp140-hsp70 Conjugate Vaccine (TL01)

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

CN54gp140 glycoprotein-hsp70 conjugate vaccine

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring HIV Infections, Acquired Immune Deficiency Syndrome

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
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.

Sites / Locations

St George's - University of London

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vaginal immunisation

Arm Description

CN54gp140 glycoprotein-hsp70 conjugate vaccine

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT01285141

First Posted

January 26, 2011

Last Updated

December 4, 2012

Sponsor

St George's, University of London

Collaborators

European Union

1. Study Identification

Unique Protocol Identification Number

NCT01285141

Brief Title

Reactogenicity and Immunogenicity of Cervico-vaginal CN54gp140-hsp70 Conjugate Vaccine

Acronym

TL01

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2012

Overall Recruitment Status

Completed

Study Start Date

July 2011 (undefined)

Primary Completion Date

January 2012 (Actual)

Study Completion Date

December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

St George's, University of London

Collaborators

European Union

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

Keywords

HIV Infections, Acquired Immune Deficiency Syndrome

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vaginal immunisation

Arm Type

Experimental

Arm Description

CN54gp140 glycoprotein-hsp70 conjugate vaccine

Intervention Type

Biological

Intervention Name(s)

CN54gp140 glycoprotein-hsp70 conjugate vaccine

Other Intervention Name(s)

ZM96gp140 glycoprotein

Intervention Description

CN54gp140-hsp70 conjugate vaccine administered intravaginally 3 times over a 12-week period

Primary Outcome Measure Information:

Title

Frequency of local immunisation site vaccine-related Adverse Events

Description

Time Frame

20 weeks

Secondary Outcome Measure Information:

Title

Frequency of generalised vaccine-related Adverse Events

Description

Time Frame

Title

Frequency of vaccine-related Adverse Events in hematology and serum biochemistry parameters

Description

Adverse Events defined as deviation from normal ranges defined for pre-determined panels of hematology and serum biochemistry parameters.

Time Frame

Title

Frequency of subjects mounting a cervico-vaginal antibody response to CN54gp140

Description

Exploratory assay of cervico-vaginal antibody to CN54gp140, measured at each scheduled study visit. Not a study endpoint.

Time Frame

20 weeks

Title

Frequency of subjects mounting a cervico-vaginal antibody response to hsp70

Description

Exploratory assay of cervico-vaginal antibody to hsp70, measured at each scheduled study visit. Not a study endpoint.

Time Frame

20 weeks

Title

Frequency of subjects mounting a T cellular proliferative response to CN54gp140

Description

Exploratory assay of T cell proliferation in response to in vitro antigen stimulation, measured at each scheduled study visit. Not a study endpoint.

Time Frame

20 weeks

Title

Frequency of subjects mounting a serum antibody response to CN54gp140

Description

Exploratory assay of serum antibody to CN54gp140, measured at each scheduled study visit. Not a study endpoint.

Time Frame

20 weeks

Title

Frequency of subjects mounting a serum antibody response to hsp70

Description

Exploratory assay of serum antibody to hsp70, measured at each scheduled study visit. Not a study endpoint.

Time Frame

20 weeks

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David JM Lewis, MD

Organizational Affiliation

St George's, University of London, UK

Official's Role

Principal Investigator

Facility Information:

Facility Name

St George's - University of London

City

London

State/Province

England

ZIP/Postal Code

SW17 0RE

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

25008917

Citation

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.

Results Reference

derived

Links:

URL

http://www.sgul.ac.uk

Description

St George's, University of London

Learn more about this trial

Reactogenicity and Immunogenicity of Cervico-vaginal CN54gp140-hsp70 Conjugate Vaccine

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