Immunization With HIV-1 Peptides in Adjuvant for Treatment of Patients With Chronic HIV-infection

NCT01009762 | Completed Phase 1 Results DMC

• 2 other identifiers: EudraCT 2008-002980-152008-002980-15
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Treatment: Immunization with a peptide-mix of 17 Clusters of Differentiation number 8 (CD8) T cell minimal epitopes and 3 Clusters of Differentiation number 4 (CD4) T cell epitopes and a new adjuvant (CAF01). The vaccine should induce cellular immunity against human immuno-deficiency virus type-1 (HIV-1). Target group: Untreated healthy individuals with chronic HIV-1 infection who are not in antiretroviral treatment. 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 new T cell immunity, lowering of HIV-1 ribonucleic acid (RNA) viral load in plasma, and improvement in the patient CD4 lymphocyte blood counts. Design: The experiment is designed as a single-blinded, placebo-controlled phase 1 clinical trial in HIV-1 infected individuals in Denmark. Numbers of individuals: 20 fully evaluable HIV-1-infected patients should enter the study (15 vaccine treated and 5 placebo(saline) treated controls). The hypothesis is that a redirection of cytotoxic T lymphocyte (CTL) immunity to selected relatively immune silent (subdominant) but conserved CTL targets on multiple sites in HIV-1 could provide a better immune control of the virus replication. This could result in lowering of viral load thereby prolonging the time to antiretroviral therapy.

Conditions

HIV INFECTIONS

Keywords

VACCINE; THERAPY; CELLULAR IMMUNITY; IMMUNITY

Outcome Measures

Primary Outcomes (1)

• Numbers of Treatment Related Side Effects (DLT = Reaction 3 or More)

  the numbers of treatment related side effects (DLT = reaction 3 or more) are registered for participants

  up to 6 months after end of treatment

Secondary Outcomes (2)

• Number of Participants With New T Cell Response to the Vaccine Target Epitopes

  10-14 days or 3 months or 6 months after last immunisation

• Numbers of Participants With Lowering of HIV RNA Viral-load

  up to 6 months after treatment stop

Study Arms (2)

Saline

PLACEBO COMPARATOR

Sterile saline for injection is used as placebo arm. It is administered i.m. in the same way as for the active vaccine, week 0, 2, 4, 8.

AFO-18 vaccine

ACTIVE COMPARATOR

the intervention is injection of the experimental therapeutic peptide vaccine (AFO-18) consisting of 18 peptides in CAF01 adjuvant intra muscularly (i.m.) week 0, 2, 4, 8

Biological: peptide vaccine (AFO-18)

Interventions

peptide vaccine (AFO-18) BIOLOGICAL

18 Peptides (250 ug of each peptide) in Adjuvant CAF01 (= 625/125 ug DDA/TDB), i.m. injection week 0, 2, 4, 8.

Also known as: DDA/TDB, peptides

AFO-18 vaccine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• HIV-1 seropositive with measurable viral load \>10e3 copies/ml and CD4+ T-cell count \>400 CD4+ cells/µl
• Not in Antiretroviral Therapy (\>1 year)
• Male or female with age between 18 and 60 years, where females are not breastfeeding, are not pregnant and use contraception until at least 3 months after end of vaccinations
• 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
• Expected to follow the instructions
• Written informed consent after oral and written information

You may not qualify if:

• Vaccinated with other experimental vaccines within 3 months before the first vaccination
• Treated with immune modulating medicine within 3 month before the first immunization
• Other significant active chronic infectious diseases likely to influence the HIV-1 infection, like Hepatitis B Virus (HBV), Hepatitis C Virus (HCV)
• Significant medical disease as judged by the investigators, for example severe asthma/chronic obstructive lung disease (COLD), badly regulated heart disease, insulin-dependent diabetes mellitus
• Severe allergy or earlier anaphylactic reactions
• Active autoimmune diseases
• Simultaneous treatment with other experimental drugs
• Laboratory parameters outside the 'normal' range for the area and which are considered clinically significant
• Pregnancy and/or brest feeding

Sponsors & Collaborators

• Gitte Kronborg: lead
• Statens Serum Institut: collaborator
• Rigshospitalet, Denmark: collaborator
• Hvidovre University Hospital: collaborator
• Ministry of the Interior and Health, Denmark: collaborator

Study Sites (1)

Department Infectious Diseases, Hvidovre university hospital

Copenhagen, DK-2650, Denmark

Location

Related Publications (2)

• Kloverpris H, Karlsson I, Bonde J, Thorn M, Vinner L, Pedersen AE, Hentze JL, Andresen BS, Svane IM, Gerstoft J, Kronborg G, Fomsgaard A. Induction of novel CD8+ T-cell responses during chronic untreated HIV-1 infection by immunization with subdominant cytotoxic T-lymphocyte epitopes. AIDS. 2009 Jul 17;23(11):1329-40. doi: 10.1097/QAD.0b013e32832d9b00.

  PMID: 19528789 BACKGROUND

• Karlsson I, Brandt L, Vinner L, Kromann I, Andreasen LV, Andersen P, Gerstoft J, Kronborg G, Fomsgaard A. Adjuvanted HLA-supertype restricted subdominant peptides induce new T-cell immunity during untreated HIV-1-infection. Clin Immunol. 2013 Feb;146(2):120-30. doi: 10.1016/j.clim.2012.12.005. Epub 2012 Dec 21.

  PMID: 23314272 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Protein Subunit Vaccines; Peptides

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Vaccines, Acellular; Vaccines, Subunit; Vaccines; Biological Products; Complex Mixtures; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Professor Anders Fomsgaard
• Organization: Statens Serum Institut

afo@ssi.dk

+45-32683460

Study Officials

• Gitte Kronborg, MD

  Hvidovre University Hospital

  PRINCIPAL INVESTIGATOR

• Anders Fomsgaard, MD

  Statens Serum Institut

  STUDY DIRECTOR

• Jan Gerstoft, MD

  University of Copenhagen

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Medical Doctor

Study Record Dates

• First Submitted: November 6, 2009
• First Posted: November 9, 2009
• Study Start: September 1, 2009
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: March 27, 2014
• Results First Posted: February 27, 2014

Record last verified: 2014-02

Locations

DK (1)