Safety and Immunogenicity Study of a DNA Vaccine Combined With Protein Vaccine Against HIV/AIDS

NCT02376582 | Completed Phase 1 DMC

• 1 other identifier: EV06
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objective of the proposed phase I trial is to evaluate the safety and tolerability of DNA-HIV-PT123 and AIDSVAX®B/E combination regimen. Though both DNA-HIV-PT123 and AIDSVAX®B/E and the combination of the two vaccines have been evaluated in humans and have shown to be safe and well tolerated, this is the first time the combination regimen is being evaluated in HIV-1 uninfected African populations with and without S. mansoni. The secondary objective of the trial is to evaluate the effect of S. mansoni infection on the immunogenicity of the combination of DNA-HIV-PT123 and AIDSVAX® B/E vaccine regimen. Successful vaccination against most viruses requires efficient Th1 response. There is evidence that helminth infections skew the host immune system of human and animals to T-helper type 2 (Th2) and induce immunosuppression. Therefore, there is a potential that helminth infected populations may not generate the desired immune responses to vaccines designed to drive Th1-type and cytotoxic T-cell responses. Furthermore, the influence of helminth infections on the development of protective antibody responses remains unclear. Limited data in animal models suggests that worm infections reduced efficacy of vaccines. The proposed vaccine trial will generate safety, tolerability and immunogenicity data of a vaccination regimen with simultaneous administration of a candidate HIV DNA vaccine (DNA-HIV-PT123) and a gp120 protein vaccine (AIDSVAX®B/E). This will be the first HIV vaccine trial to prospectively evaluate the impact of the S. mansoni infection on safety and immune responses to HIV vaccines.

Conditions

HIV/AIDS

Keywords

HIV/AIDS vaccine; helminth infection; Impact of co-infection

Outcome Measures

Primary Outcomes (4)

• Proportion of volunteers with local and systemic reactogenicity events during a 7 day follow up period after each vaccination

  7 days post each vaccination

• Proportion of volunteers with adverse events during a 4 week follow up period after each vaccination

  4 weeks post each vaccination

• Proportion of volunteers with abnormal laboratory parameters during a 4 week follow up period after each vaccination

  4 weeks post each vaccination

• Proportion of volunteers with serious adverse events throughout the study period

  Each participant will be followed for 9 months

Secondary Outcomes (4)

• Proportion of volunteers with HIV-specific CD4+ and CD8+ T cell responses as assessed by IFN-g ELISpot and multiparameter flow cytometry (IFN-g TNF-a and IL-2) 2 weeks after the 2nd and 3rd vaccination

  two weeks post 2nd and 3 vaccination

• Magnitude of HIV-specific CD4+ and CD8+ T cell responses as assessed by IFN-g ELISpot and multiparameter flow cytometry (IFN-g TNF-a and IL-2) 2 weeks after the 2nd and 3rd vaccination

  two weeks post 2nd and 3 vaccination

• HIV-specific Env binding Antibody response 2 weeks after the 2nd and 3rd vaccination

  two weeks post 2nd and 3 vaccination

• Magnitude and breadth of neutralizing antibody responses against tier 1 and tier 2 HIV-1 isolates 2 weeks after the 2nd and 3rd vaccination

  two weeks post 2nd and 3 vaccination

Study Arms (2)

DNA and protein

EXPERIMENTAL

4mg DNA and 600 mcg protein formulated with Alum co-administration (IM) at Month 0, 1 and 6 in Schisto infected individuals

Biological: DNA; Biological: AIDSVAX B/E

Vaccination without S. mansoni infection

ACTIVE COMPARATOR

DNA Protein

Biological: DNA; Biological: AIDSVAX B/E

Interventions

DNA BIOLOGICAL

DNA co-administered with protein at month 0, 1 and 6

Also known as: DNA-HIV-PT123

DNA and protein; Vaccination without S. mansoni infection

AIDSVAX B/E BIOLOGICAL

Protein co-administered with DNA at month 0,1 and 6

DNA and protein; Vaccination without S. mansoni infection

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• HIV-1 uninfected adults aged 18-45 years, as confirmed by a medical history, physical exam, and laboratory tests during screening
• In 50% of study volunteers, positive for S. mansoni infection but negative for other helminth infections.
• In 50% of study volunteers, negative for S. mansoni and other helminth infections
• Willing to forgo treatment with praziquantel until after completion of week 26 visit in the trial.
• Able and willing to provide written informed consent prior to screening
• Aged 18 through 45 years on the day of first vaccination
• Able and willing to complete screening (about 1 month) and available for the planned follow-up period (9months)
• Willing to undergo HIV testing, risk reduction counselling, receive HIV test results and committed to maintaining low risk behaviour for the trial duration
• If female of childbearing potential (not menopausal or sterilised), willing to use a non-barrier contraceptive method from screening through the end of the study. Acceptable contraceptive methods include hormonal contraceptives (injection, transdermal patch, or implant) and intrauterine device (IUD).
• Willing to provide blood, urine and stool samples for laboratory examination

You may not qualify if:

• HIV-1 infection
• Infection with other helminths
• Symptomatic and asymptomatic malaria infection (presence of malaria parasites on thick blood smear)
• Treatment with praziquantel in the past 3 months
• S. mansoni egg count of\>2000 eggs per gram of stool
• Clinically significant acute or chronic illness at the time of randomization.
• Any clinically relevant abnormality on history or examination
• Use of immunosuppressive medication (other than inhaled or topical immunosuppressants)
• Receipt of immunoglobulin within past 60 days
• Abnormal laboratory values as specified below from blood collected within 28 days prior to randomization:
• Hematology
• Haemoglobin \<9.0 g/dL or\<5.59 mmol/L
• Absolute Neutrophil Count (ANC): \< 1000/mm3or \< 1.0 x 109/L
• Absolute Lymphocyte Count (ALC): ≤ 500/mm3or ≤ 0.5 x 109/L
• Platelets: ≤ 90,000 ≥ 550,000/mm3or ≤ 90 x 109 ≥ 550 x 109/L

Sponsors & Collaborators

• EuroVacc Foundation: lead
• International AIDS Vaccine Initiative: collaborator
• Medical Research Council: collaborator
• MRC/UVRI and LSHTM Uganda Research Unit: collaborator
• Centre Hospitalier Universitaire Vaudois: collaborator

Study Sites (2)

Uganda Virus Research Institute - International AIDS Vaccine Initiative HIV Vaccine Program (UVRI-IAVI)

Entebbe, Uganda

Location

Medical Research Council (MRC) /Uganda Virus Research Institute (UVRI)

Masaka, Uganda

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Trematode Infections

Interventions

DNA; AIDSVAX B-E

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Helminthiasis; Parasitic Diseases

Intervention Hierarchy (Ancestors)

Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Pontiano Kaleebu

  Medical Research Council (MRC) / Uganda Virus Research Institute (UVRI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2014
• First Posted: March 3, 2015
• Study Start: September 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: January 22, 2016

Record last verified: 2016-01

Locations

UG (2)