The Safety and Immunogenicity of a Potential HIV Vaccine

Study Overview
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Brief Summary
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The potential HIV vaccine has two components: a protein immunogen based on the coat protein of HIV; and an adjuvant which enhances the vaccinee's response to the immunogen. The immunogen is CN54gp140, and the adjuvant is glucopyranosyl lipid adjuvant - aqueous formulation (GLA-AF). We wish to assess the vaccine's safety and immunogenicity (the nature of the immune response stimulated by the vaccine) when it is given in two different dose regimens: Group A: vaccinations at Months 0, 1, 2 and 6; and Group B: vaccinations at Months 0, 1, 2 and 12. Each dose will be an intramuscular injection of 100 micrograms of CN54gp140 mixed with 5 micrograms of GLA-AF. We will recruit only healthy, HIV-uninfected men and women. We will assess the safety of the vaccine by monitoring the occurrence of adverse events in the participants. We will assess the immunogenicity of the vaccine by monitoring the immune response to the vaccine in blood and in genital mucosal secretion samples.

Official Title
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A Phase 1 Open-Labelled Trial to Evaluate the Safety and Immunogenicity of CN54gp140 in HIV-Uninfected, Healthy Volunteers

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: CN54gp140 mixed with GLA-AF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female, as assessed by medical history, physical exam, and laboratory tests; At least 18 years of age on the day of screening and has not reached his/her 46th birthday on the day of first vaccination; Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study; Willing and able to give written informed consent; Willing to undergo HIV testing, receive HIV test results and be committed to maintaining low risk behaviour for the trial duration; If a female who is sexually active with male partner(s), willing to use an effective method of contraception from screening until at least 4 months after the last study vaccination [e.g., hormonal contraceptives, consistent record with condoms, physiological or anatomical sterility in self or partner, but excluding intrauterine device (IUD) which would preclude the collection of cervico-vaginal secretions with Softcup]; All female volunteers must be willing to undergo urine pregnancy tests at time points indicated in the Schedule of Procedures (Appendices A-B) and must test negative prior to each study vaccination; All sexually active males (unless anatomically sterile or in a monogamous relationship with a female partner who uses a documented non-barrier method of birth control) must be willing to use an effective method of contraception (e.g., consistent condom use) from the day of first vaccination until at least 4 months after the last vaccination; Willing to forgo donations of blood or any other tissues during the study and, for those who test HIV-positive due to trial vaccination (vaccine-induced HIV seropositivity), until the anti-HIV antibody titres become undetectable. Registered with a general practitioner for at least the past three months Exclusion Criteria: Confirmed HIV-1 or HIV-2 infection; Any clinically relevant abnormality on history or examination including history of immunodeficiency or autoimmune disease; use of systemic corticosteroids (the use of topical or inhaled steroids is permitted); immunosuppressive, anti-cancer, anti-tuberculosis or other medications considered significant by the investigator within the previous 6 months; Any clinically significant acute or chronic medical condition that is considered progressive, or in the opinion of the investigator, makes the volunteer unsuitable for participation in the study; Reported risky behaviour for HIV infection within the 6 months prior to vaccination as defined by: history of injecting drug use in the previous ten years; gonorrhoea or syphilis in the last six months; high risk partner (e.g. injecting drug use, HIV positive partner) either currently or within the past six months; unprotected anal intercourse in the last six months, outside a relationship with a regular partner known to be HIV negative; or unprotected vaginal intercourse in the last six months outside a relationship with a regular known/presumed HIV negative partner. Reported abnormal cervical cytology or previous or ongoing treatment for Cervical Intraepithelial Neoplasia; If female, pregnant or planning a pregnancy within 4 months after last study vaccination; or lactating; Bleeding disorder that was diagnosed by a physician (e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions) (Note: A volunteer who states that he or she has easy bruising or bleeding, but does not have a formal diagnosis and has intramuscular injections and blood draws without any adverse experience, is eligible); History of splenectomy; Any of the following abnormal laboratory parameters listed below: haemoglobin <11.0 g/dL; absolute neutrophil count (ANC) ≤ 1.3 x 109/L; absolute lymphocyte count (ALC) ≤ 0.9 x 109/L; platelets ≤ 125 x 109/L; creatinine >1.1 x upper limit of normal (ULN); aspartate aminotransferase >1.25 x ULN; alanine aminotransferase >1.25 x ULN; clinically significant abnormal urinalysis dipstick confirmed by microscopy (protein 2+ or more, blood 2+ or more not due to menses); positive for hepatitis B surface antigen (HbsAg), hepatitis C (HCV antibodies) or active syphilis; Receipt of live-attenuated vaccine within the previous 60 days or planned receipt within 60 days after vaccination with Investigational Product; or receipt of other vaccine, allergy treatment with antigen injections or tuberculin skin test within the previous 14 days or planned receipt within 14 days after vaccination with Investigational Product; Receipt of blood transfusion or blood-derived products within the previous 3 months; Participation in another clinical trial of an Investigational Product currently, within the previous 3 months or expected participation during this study; Prior receipt of another investigational HIV vaccine candidate (Note: receipt of placebo in a previous HIV vaccine trial will not exclude a volunteer from participation if documentation is available); History of severe local or systemic reactogenicity to vaccines (e.g., anaphylaxis, respiratory difficulty, angioedema); Psychiatric condition that compromises safety of the volunteer and precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years; Seizure disorder: a participant who has had a seizure in the last 3 years is excluded. (Not excluded: a participant with a history of seizures who has neither required medications nor had a seizure for 3 years.); If female, history of toxic shock syndrome (TSS), which would preclude the use of Softcup; If female, current use of intrauterine device (IUD), which would preclude the use of Softcup; If, in the opinion of the Principal Investigator, it is not in the best interest of the volunteer to participate in the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>Biological/Vaccine: CN54gp140 mixed with GLA-AF Vaccination at Months 0, 1, 2 and 6; each vaccination an intramuscular injection of 100 micrograms CN54gp140 mixed with 5 micrograms GLA-AF | Biological: CN54gp140 mixed with GLA-AF<br>* Each vaccination an intramuscular injection of 100 micrograms CN54gp140 mixed with 5 micrograms GLA-AF<br>|
| Active Comparator: Group B<br>Biological/Vaccine: CN54gp140 mixed with GLA-AF Vaccination at Months 0, 1, 2 and 12; each vaccination an intramuscular injection of 100 micrograms CN54gp140 mixed with 5 micrograms GLA-AF | Biological: CN54gp140 mixed with GLA-AF<br>* Each vaccination an intramuscular injection of 100 micrograms CN54gp140 mixed with 5 micrograms GLA-AF<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Moderate or Greater Reactogenicity (i.e., Solicited Adverse Events) |  | 7 days | 
| Number of Participants With Moderate or Greater and/or Vaccine-related Unsolicited Adverse Events (AEs) | Including safety laboratory (biochemical, haematological) parameters, from the day of each vaccination up to 28 days post each vaccination. | 28 days | 
| Number of Participants With Vaccine Related Serious Adverse Events (SAEs) Collected Throughout the Study Period |  | 13 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human immunodeficiency disease, HIV, Vaccine, CN54gp140, Glucopyranosyl lipid adjuvant, GLA, GLA-AF