Safety and Immunogenicity of HIV DNA-C CN54ENV and Recombinant HIV CN54gp140 Vaccines in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
CUTHIVAC002 is a randomised Phase I study aimed at exploring the safety and immunogenicity of two different modes of delivery of a deoxyribonucleic acid (DNA) vaccine (DNA-C CN54ENV) via combined intramuscular and intradermal methods with and without electroporation, and boosted with recombinant HIV CN54gp140 administered by intradermal injection in healthy volunteers. The aim of this study is to identify optimal DNA delivery conditions for promoting enhanced antibody responses to boosting with recombinant protein by the intradermal method.

Detailed Description
-----------------
CUTHIVAC002 is a randomised Phase I study in healthy volunteers, aimed at exploring the safety and immunogenicity of two different modes of delivery of a deoxyribonucleic acid (DNA) HIV vaccine via combined intramuscular and intradermal methods with and without electroporation (EP), and boosted with recombinant HIV protein vaccine administered by intradermal injection without EP. The aim of this study is to identify optimal DNA delivery conditions for promoting enhanced antibody responses to boosting with recombinant protein by the intradermal route. Healthy male and female volunteers aged 18 to 50 years old, who are at low risk of HIV infection, are to be recruited. The participants will be divided into 3 groups: Group 1: Participants will receive 1 x 0.15 ml (0.6 mg) DNA intradermal injections into the upper arm with EP and 1 x 0.5 ml (2 mg) intramuscular injection into the upper thigh without EP at Weeks 0, 4 & 8. And also 1 x 0.1 ml (50 μg) HIV recombinant protein by intradermal injection into the upper arm at Week 20 (final vaccination). Group 2: Participants will receive 1 x 0.15 ml (0.6 mg) DNA intradermal injections into the upper arm without EP and 1 x 0.5 ml (2 mg) intramuscular injection into the upper thigh with EP at weeks 0, 4 & 8. And also 1 x 0.1 ml (50 μg) HIV recombinant protein by intradermal injection into the upper arm at Week 20 (final vaccination). Group 3: Participants will receive 1 x 0.15 ml (0.6 mg) of DNA of intradermal injections into the upper arm with EP and 1 x 0.5 ml (2 mg) intramuscular injection into the upper thigh with EP at weeks 0, 4 & 8. And also 1 x 0.1 ml (50 μg) HIV recombinant protein by intradermal injection into the upper arm at Week 20 (final vaccination). The investigators aim to have 8 participants complete the study in each group.

Official Title
-----------------
A Phase I Clinical Trial to Assess the Safety and Immunogenicity of HIV DNA-C CN54ENV Immunisations Administered Via the Intramuscular and Intradermal Methods With and Without Electroporation Followed by Boosting With Recombinant HIV CN54gp140 in Healthy Male and Female Volunteers

Conditions
-----------------
HIV

Intervention / Treatment
-----------------
* Biological: DNA-C CN54ENV
* Biological: CN54gp140
* Device: Trigrid Delivery System - Intramuscular
* Device: Trigrid Delivery System - Intradermal


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women aged between 18 and 50 years on the day of screening BMI between 18-30 Available for follow-up for the duration of the study ( 5 months from screening) Willing and able to give written informed consent At low risk of HIV and willing to remain so for the duration of the study defined as: no history of injecting drug use in the previous ten years no gonorrhoea or syphilis in the last six months no high risk partner (e.g. injecting drug use, HIV positive partner) either currently or within the past six months no unprotected anal intercourse in the last six months, outside a relationship with a regular partner known to be HIV negative no unprotected vaginal intercourse in the last six months outside a relationship with a regular known/presumed HIV negative partner Willing to undergo a HIV test Willing to undergo a genital infection screen Must agree to require male sexual partner to use condoms, from at least 14 days before the first vaccination until at least 14 days after the last If heterosexually active female capable of becoming pregnant, must (in addition to requiring male partner to use condoms) agree to use hormonal contraception, or to complete abstinence, from at least 14 days before the first vaccination until at least 14 days after the last. [Note: Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal, and IUD/IUS, are not acceptable methods of contraception.] If sexually active male, must agree to use condoms from the day of first vaccination until at least 14 days after the last. [Note: Additional use of an effective method of contraception is recommended for any non-pregnant female partner over the same period.] Agree to abstain from donating blood for three months after the end of their participation in the trial, or longer if necessary Registered with a GP for at least the past three months Entered and clearance obtained from The Over-volunteering Prevention System (TOPS) database. Exclusion Criteria: Pregnant or lactating History of cardiac arrhythmia or palpitations [e.g., supraventricular tachycardia, atrial fibrillation, frequent ectopy, or sinus bradycardia prior to study entry (sinus arrhythmia is not excluded) History of syncope or fainting episodes within 1 year of study entry History of grand-mal epilepsy, seizure disorder or any history of prior seizure Individuals in which a skin-fold measurement (cutaneous and subcutaneous tissue) of the upper right or left thigh exceeds 40 mm Clinically relevant abnormality on history or examination Known hypersensitivity to any component of the vaccine formulations used in this trial, or have severe or multiple allergies to drugs or pharmaceutical agents History of severe local or general reaction to vaccination defined as local: extensive, indurated redness and swelling involving most of the antero-lateral thigh or the major circumference of the arm, not resolving within 72 hours general: fever ≥39.5 °C within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours Receipt of live attenuated vaccine or HIV envelope components within 60 days or other vaccines within 14 days of enrolment Receipt of an experimental vaccine containing HIV envelope components at any time in the past Receipt of blood products or immunoglobulin within 4 months of screening Participation in another trial of a medicinal product, completed less than 30 days prior to enrolment. HIV 1 or 2 positive or indeterminate on screening. Positive for hepatitis B surface antigen, hepatitis C antibody or serology indicating active syphilis requiring treatment Grade 1 or above routine laboratory parameters. Hyperbilirubinaemia to be considered an exclusion criterion only when confirmed to be conjugated bilirubinaemia Current use of any electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators. Presence of any surgical or traumatic metal implants at the sites of administration Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent. Women with a history of toxic shock syndrome. Women using an intrauterine device for contraception (as incompatible with softcup sampling) Unlikely to comply with protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: ID/EP + IM<br>0.6 mg DNA-C CN54ENV, intradermally with electroporation, at Weeks 0, 4 and 8. 2 mg DNA-C CN54ENV, intramuscularly without electroporation, at Weeks 0, 4 and 8. 50 µg CN54gp140, intradermally without electroporation, at Week 20. | Biological: DNA-C CN54ENV<br>* DNA plasmid containing the Clade C gp140 envelope gene from HIV-1 isolate CN54<br>Biological: CN54gp140<br>* Recombinant protein expressed from the Clade C gp140 envelope gene from HIV-1 isolate CN54<br>Device: Trigrid Delivery System - Intradermal<br>* Electroporation<br>* Other names: TDS-ID;|
| Experimental: Group 2: ID + IM/EP<br>0.6 mg DNA-C CN54ENV, intradermally without electroporation, at Weeks 0, 4 and 8. 2 mg DNA-C CN54ENV, intramuscularly with electroporation, at Weeks 0, 4 and 8. 50 µg CN54gp140, intradermally without electroporation, at Week 20. | Biological: DNA-C CN54ENV<br>* DNA plasmid containing the Clade C gp140 envelope gene from HIV-1 isolate CN54<br>Biological: CN54gp140<br>* Recombinant protein expressed from the Clade C gp140 envelope gene from HIV-1 isolate CN54<br>Device: Trigrid Delivery System - Intramuscular<br>* Electroporation<br>* Other names: TDS-IM;|
| Experimental: Group 3: ID/EP + IM/EP<br>0.6 mg DNA-C CN54ENV, intradermally with electroporation, at Weeks 0, 4 and 8. 2 mg DNA-C CN54ENV, intramuscularly with electroporation, at Weeks 0, 4 and 8. 50 µg CN54gp140, intradermally without electroporation, at Week 20. | Biological: DNA-C CN54ENV<br>* DNA plasmid containing the Clade C gp140 envelope gene from HIV-1 isolate CN54<br>Biological: CN54gp140<br>* Recombinant protein expressed from the Clade C gp140 envelope gene from HIV-1 isolate CN54<br>Device: Trigrid Delivery System - Intramuscular<br>* Electroporation<br>* Other names: TDS-IM;Device: Trigrid Delivery System - Intradermal<br>* Electroporation<br>* Other names: TDS-ID;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as assessed by adverse events | Adverse events | From first dose until up to Week 22 | 
| Immunogenicity as assessed by the magnitude of antigen-specific systemic IgG antibody binding responses (µg/mL) at Week 22 (2 weeks after the final vaccination) | Immune response to vaccination | Week 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the electroporation devices as assessed by adverse events | Adverse events at the ID and IM injection sites that start within 7 days after Doses 1-3 | From Dose 1, 2 and 3 until 7 days later | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
safety, immunogenicity, HIV vaccine