Clinical trial NCT01141205: HIV-1 Peptide Immunisation of Individuals in West Africa to Prevent Disease
Official title: Phase I Study: HIV-1 Peptide Immunisation of Individuals in West Africa to Prevent Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Aids, Cdc Group I
Keywords: AIDS vaccines
HIV-1 vaccine
Therapeutic vaccine
Cellular immunity
Lead sponsor: Statens Serum Institut
Sponsor class: OTHER
Collaborators: name: Ministry of the Interior and Health, Denmark
name: European and Developing Countries Clinical Trials Partnership (EDCTP)
First posted: 2010-06-10
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Treatment: Immunization with peptide-mix and adjuvant. The vaccine should induce cellular immunity against HIV-1.

Target group: Untreated healthy individuals with chronic HIV-1 infection.

Purpose: The primary purpose is to evaluate tolerability and safety of the vaccine.

The secondary purpose is to evaluate the clinical effect of the vaccination treatment as measured by induction of immunity, lowering of viral load, induction of escape mutations in the virus and improvement in the patient CD4 lymphocyte blood counts.

The third purpose is to evaluate the feasibility of conducting a therapeutic HIV immunization study in a poorly-resourced African setting.

Design: The experiment is designed as a blinded, placebo-controlled phase 1 clinical trial in HIV-1 infected individuals in West Africa.

Numbers of individuals: Phase I: 20 fully evaluable HIV-1-infected patients should enter the study (15 vaccine treated and 5 placebo(saline) treated controls).

Detailed description: The HIV infection does not leave lifelong immunity, but leads to break down of the immune system, opportunistic infections and death. The immunity obtained by the infection itself can only partially contain the HIV infection. The purpose with a targeted therapeutic vaccination is therefore in addition to the existing immunity to induce a broader, more powerful and more rationally or better directed immunity than the one induced by the "natural" HIV-1 infection. This would potentially lower the viral load in the blood making it more difficult to spread the virus to others and prolong the time to AIDS disease and medical treatment. There is a need for new rational vaccination possibilities, able to prevent (HIV) disease, postpone the need for antiretroviral medical treatment, prolong the life, and limit spread of HIV-1 in the population. The present protocol seak to introduce such a new immune treatment principle for HIV-1 infected individuals. In this study, individuals with chronic HIV-1 infection will be vaccinated with selected synthetic HIV immune-peptides representing new discovered conserved target´s on the virus. The vaccine should induce new immunity against several epitope targets on their HIV, whereby the HIV infection may be controlled for a longer time by the immune system. The purpose of the study is primarily to evaluate the safety and tolerability of the vaccine and secondary to evaluate the immunological and antiviral response in the vaccinated individuals.

Eligibility criteria: Inclusion Criteria:

1. HIV-1 seropositive with measurable viral load \>10e3 copies/ml and CD4+ T-cell count \>400 CD4+ cells/µl.
2. Not in Antiretroviral Therapy (\>1 year).
3. Male or female with age between 18 and 50 years.
4. Normal values for the area of liver and kidney enzymes, blood cell count with differential counts (e.g. white blood cells, lymphocytes, platelets/thrombocytes) and Hemoglobin
5. Expected to follow the instructions.
6. Written informed consent after oral and written information.

Exclusion Criteria:

1. Vaccinated with other vaccines within 3 months before the first vaccination.
2. Treated with immune modulating medicine within 3 month before the first immunization.
3. Other important active chronic infectious diseases likely to influence the HIV-1 infection, like HIV-2, HBV, HCV and TB
4. Significant medical disease as judged by the investigators, for example severe asthma/COLD, badly regulated heart disease, insulin-dependent diabetes mellitus.
5. Severe allergy or earlier anaphylactic reactions.
6. Active autoimmune diseases.
7. Simultaneous treatment with other experimental drugs.
8. Laboratory parameters outside the 'normal' range for the area and which are considered clinically significant.
9. Pregnancy

Primary outcomes:
measure: Tolerability and Safety of the Treatment.
timeFrame: up to 6 months after end of treatment
Secondary outcomes:
measure: Induction of New T-cell Immune Response by the Vaccine
timeFrame: up to 6 months after last immunisation
measure: Lowering of HIV-1 RNA Viral-load in HIV-1 Immune Responders More Than 1 Log
timeFrame: up to 6 months post immunization
measure: Increase in Blood CD4 T-cell Counts
timeFrame: up to 6 months post vaccination
Other outcomes:
Locations:
city: Bissau
country: Guinea-Bissau
facility: Hospital Nacional Simao Mendes
Study officials:
affiliation: Statens Serum Institut
name: Anders Fomsgaard, DMSc
role: STUDY_DIRECTOR
affiliation: Bandim Health Project, Bissau, Guinea-Bissau
name: Zacarias Jose da Silva, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roman VR, Jensen KJ, Jensen SS, Leo-Hansen C, Jespersen S, da Silva Te D, Rodrigues CM, Janitzek CM, Vinner L, Katzenstein TL, Andersen P, Kromann I, Andreasen LV, Karlsson I, Fomsgaard A. Therapeutic vaccination using cationic liposome-adjuvanted HIV type 1 peptides representing HLA-supertype-restricted subdominant T cell epitopes: safety, immunogenicity, and feasibility in Guinea-Bissau. AIDS Res Hum Retroviruses. 2013 Nov;29(11):1504-12. doi: 10.1089/AID.2013.0076. Epub 2013 Jun 21.