Safety, Tolerability and Immunogenicity Induced by the THV01 Treatment in Patients Infected With HIV-1 Clade B and Treated With Highly Active Antiretroviral Therapy (HAART).
Condition: HIV Infection
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The objectives of this Phase I/II trial is to evaluate the safety, tolerability and
      immunogenicity of THV01 compared to placebo in HIV-1 infected patients on HAART (highly
      active antiretroviral therapies).

      THV01 is composed of two vaccines that derived from the HIV (human immunodeficiency virus):
      lentiviral vectors. They are non-replicative and not infectious. They will be injected
      intramuscularly, eight weeks apart. Three doses will be assessed and compared to placebo.

      Eligible patients must have an undetectable viral load and must be treated by HAART for more
      than 12 months. They will be randomly allocated to one of the study group and will receive
      the experimental drugs at one of the three doses or a matching placebo.

      Their anti-HIV treatment will be alleviated around each experimental drugs' administration to
      enable THV01 efficacy. HAART will be resumed one week after the second injection. 15 weeks
      after resumption, HAART will be interrupted. Patients will then be monitored every 2 weeks
      for CD4+ T cell counts and viral load as well as for thorough assessment of the elicited
      immune response. Stringent anti-HIV treatments resumption criteria have been implemented,
      based on the CD4+ T cell counts and the viral load.

      38 patients were enrolled in THV01-11-01 study and received the 2 injections.

      A long-term follow-up of all enrolled patients will be performed for 5 years post-prime
      administration. This will provide additional data on the safety and the potential long-term
      risks/benefits associated with THV01.

      The final study report will be written after the last patient last visit in the long-term
      follow-up.
    

Detailed description: 
      This Phase I/II is a randomized, double-blind and placebo controlled study to assess safety,
      tolerability and immunogenicity of THV01 at three doses in patients infected with the HIV-1
      clade B currently on HAART (highly active antiretroviral therapies).

      THV01 involves two intramuscular injections, consisting of the THV01-1 and THV01-2 lentiviral
      vectors, to be administered intramuscularly eight weeks apart. These lentiviral vectors are
      non-replicative and self-inactivating. Both encode the same HIV antigen.

      36 patients were planned to be enrolled. They must be HIV-1 (clade B) infected patients,
      treated by HAART for more than 12 months and with an undetectable viral load.

      Patients will be randomly allocated to one of the groups:

        -  Group 1: patients will receive the THV01-1 and THV01-2 vaccines at 5.10E+6 TU
           (transducing unit) or placebo;

        -  Group 2: patients will receive the THV01-1 and THV01-2 vaccines at 5.10E+7 TU
           (transducing unit) or placebo;

        -  Group 3: patients will receive the THV01-1 and THV01-2 vaccines at 5.10E+8 TU
           (transducing unit) or placebo.

      Hence, twelve patients will be randomized in blocks of 4 in a 3:1 ratio (vaccine:placebo) for
      each dose.

      Experimental drugs' injection will occur at Week 0 and Week 8. HAART will be alleviated for
      all patients during this "vaccination phase" to enable efficient transduction of the host
      cells by the lentiviral vectors. Initial HAART will be resumed at Week 9.

      Starting on Week 24, HAART will be interrupted. Patients will then be monitored on a very
      stringent rhythm. HAART resumption criteria based on the CD4+ T cell counts and the viral
      load have been implemented to guaranty safety of all enrolled patients.

      38 patients were enrolled in THV01-11-01 study and received the 2 injections.

      A long-term follow-up of all enrolled patients will be performed for 5 years after the
      administration of THV01-1. During this follow-up, three visits are planned per year, during
      which blood will be sampled. This will provide data on the long-term safety of THV01 and the
      potential long-term risks/benefits associated with THV01.
    

Intervention name(s): THV01-1; THV01-2; Placebo
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Intramuscular injection of THV01-1 (week 0); Intramuscular injection of THV01-2 (week 8); Intramuscular injection of placebo matching THV01-1 and THV01-2
Other intervention name(s): lentiviral vector ancoding an HIV antigen; lentiviral vector encoding an HIV antigen; Placebo matching THV01-1 and THV01-2
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment