Immunotherapy With Vacc-C5 With Adjuvant GM-CSF or Alhydrogel in HIV-1-infected Subjects on ART
Condition: HIV-1 Infection
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Background:

      Despite the introduction of highly effective antiretroviral therapy (ART) regimes, which
      control the HIV infection and results in increases in CD4 cell counts and an undetectable
      viral load, many patients suffer from increased morbidity. There is evidence that presence of
      antibodies against the C5 region of gp120 strongly correlates with slower disease
      progression, and that loss of antibody responses to this region are associated with
      progression.

      Investigational product:

      Vacc-C5 is a single heterodimeric peptide-based HIV therapeutic vaccine corresponding to the
      C5 region on gp120 and the external domain of gp41. The vaccine is intended to create a
      non-neutralizing antibody against C5 region.

      Study objectives:

        1. To evaluate safety of the vaccination regimens

        2. To evaluate C5-specific humoral immune responses (antibodies), T cell responses, T cell
           activation markers and other immune markers.
    

Detailed description: 
      Background:

      Despite the introduction of highly effective antiretroviral therapy (ART) regimes, which
      control the HIV infection and results in increases in CD4 cell counts and an undetectable
      viral load, many patients suffer from increased morbidity. There is evidence that presence of
      antibodies against the C5 region of gp120 strongly correlates with slower disease
      progression, and that loss of antibody responses to this region are associated with
      progression.

      Investigational product:

      Vacc-C5 is a single heterodimeric peptide-based HIV therapeutic vaccine corresponding to the
      C5 region on gp120 and the external domain of gp41. The rationale behind the Vacc-C5 is the
      finding that long-term non-progressors (LTNP) subjects have more antibodies towards the C5
      part of gp120 than HIV infected subjects with a more rapid disease progression.

      The primary objective of Vacc-C5 immunotherapy is to induce a humoral immune response. The
      vaccine is intended to create a non-neutralizing antibody against the C5 region and to
      thereby mimic a natural process in HIV-infected long-term non-progressors (LTNP) subjects.

      Use of adjuvant:

      Peptide vaccines are poorly immunogenic by themselves. To induce measurable levels of T
      helper cell type 1 (Th1) or type 2 (Th2) immune responses against these peptides, an adjuvant
      is often required.

      Two different adjuvants are to be used in this study:

        1. GM-CSF which facilitates dendritic cell maturation and migration to the lymph nodes for
           antigen presentation. The regimen when using this adjuvant is intradermal
           administration.

        2. Aluminum-containing adjuvants is well known. They have been administered to human beings
           and animals in millions of doses of vaccines. This type of vaccine is usually
           administered intramuscularly or subcutaneously. In this study intramuscular
           administration will be used.

      Primary objective:

      It is to evaluate the safety of Vacc-C5 at three different dose levels given intradermally
      with GM-CSF as adjuvant or given intramuscularly with Alhydrogel as adjuvant.

      Secondary objectives:

        1. To evaluate C5-specific humoral immune responses (antibodies).

        2. To evaluate the C5-specific T cell responses by ELISPOT and T cell proliferation.

        3. To evaluate T cell activation markers (e.g. CD38, HLA-DR) and other immune markers.

      Study design:

      The study is an open, dose-escalating, single centre study in HIV-positive subjects on
      treatment (ART). Two different vaccine regimens will be tested:

        1. Arm A: Vacc-C5 with GM-CSF as adjuvant administered intradermally.

        2. Arm B: Vacc-C5 with Alhydrogel as adjuvant administered intramuscularly.

      Three dose levels of Vacc-C5 (100, 300 and 900 microgram will be tested for each of the two
      vaccination regimen. A dose escalation design (3+3) will be used, and if no dose limiting
      toxicity (DLT) is detected 18 subjects will be included in each arm.

      Subjects who have been HIV-positive and stable on ART for the last 6 months with CD4 cell
      counts ≥400x 10 6 /L and who meet the other inclusion and exclusion criteria will be eligible
      for the study. The duration of the study is 26 weeks plus a screening period of up to 12
      weeks.

      During the Treatment Period, all subjects will remain on their ART and receive three
      immunizations; at Weeks 1, 2 and 4, with Vacc C5 including either GM-CSF or Alhydrogel as
      adjuvant.

      The study is sequential, meaning that the first three subjects in each arm receive the lowest
      dose (three subjects) 100 µg Vacc-C5. If no dose limiting toxicity has been detected after
      week 4 vaccination, three more subjects will be added and the next dose level will be
      started.
    

Intervention name(s): Vacc-C5/GM-CSF; Vacc-C5/Alhydrogel
Intervention type(s): Drug; Drug
Intervention description(s): Arm 1=Arm A: Vacc-C5 with GM-CSF as adjuvant administered intradermally.; Arm 2=Arm B: Vacc-C5 with Alhydrogel as adjuvant administered intramuscularly.
Other intervention name(s): Vacc-C5 = C5-peptide; GM-CSF = Leukine; Vacc-C5 = C5-pepide; Alhydrogel = Aluminum-containing adjuvant
Intervention MeSH terms: Molgramostim; Aluminum Hydroxide; Sargramostim
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HIV-1, Vacc-C5