Malaria Vaccine Safety and Immunogenicity Study in Healthy Adults
Condition: Malaria Vaccine
MeSH terms: Malaria
Intervention: RTS,S/AS01B Fractional dose; Double RTS,S/AS01E Fractional dose; RTS,S/AS01E Standard dose; RTS,S/AS01E + DHA-PIP+PQ Standard dose; RTS,S/AS01E Fractional dose; RTS,S/AS01E + DHA-PIP+PQ Fractional dose; RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose
Intervention description: RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.; A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.; RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.; RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2; RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.; RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.; RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized 7 groups
Masking: None (Open Label)
Enrollment: 193.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: safety; immunogenicity

Summary:

      Targeted malaria elimination (TME), which comprises appropriate case management by village
      health workers, vector control and mass drug administration, is currently being implemented
      through pilot projects in selected villages in the Greater Mekong Subregion (GMS) and the
      scale-up of the intervention to the regional level are underway. Based on mathematical
      modelling, extending the post-TME parasitaemia-free period in the majority of villagers for
      as short as 200 days will substantially increase the chances of achieving the interruption of
      malaria transmission. Immunogenicity of RTS,S is greater in older children, and the short
      term malaria protective effect is stronger than the overall effect assessed over 1-2 years.
      Addition of mass RTS,S/AS01E vaccination to the TME arsenal could provide this much needed
      additional protection.

      Currently there are no safety and immunogenicity data for the use of RTS,S/AS01 in Asian
      populations. This trial will generate the required data for the use of this vaccine in Asian
      populations. For integration with the current TME activities, which provide mass drug
      administrations at months M0, M1, and M2, it would be most efficient and practical to provide
      the vaccine at the same intervals. To address a two round intervention (M0, M2) where a three
      round intervention is not feasible, one study arm will look at the immune response generated
      by only two doses of vaccine and antimalarial medications. Recent evidence suggests that a
      vaccination schedule which includes a fractional dose of RTS,S/AS01 (1/5th of the standard
      dose) could be similarly or more protective than a schedule with three standard full doses,
      while requiring less vaccine and resources. The trial therefore includes study arms which
      will assess the safety and immunogenicity of fractional dose schedules.

      Each participant will be randomized into one of the following study arms in a ratio of
      20:20:30:30:30:30:30, as follows:

        -  RTS,S/AS01B Fractional dose group (Group 1)

        -  Double RTS,S /AS01E Fractional dose group (Group 2)

        -  RTS,S/AS01E Standard dose group (Group 3)

        -  RTS,S/AS01E + DHA-PIP+PQ Standard dose group (Group 4)

        -  RTS,S/AS01E Fractional dose group (Group 5)

        -  RTS,S/AS01E + DHA-PIP+PQ Fractional dose group (Group 6)

        -  RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose group (Group 7)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant is a healthy male or non-pregnant female, aged 18 to 55 years (inclusive),
             of Thai origin.

          -  Participant is willing and able to give informed consent to participate in the trial

          -  Able, in the investigators opinion, and willing to comply with the study requirements
             and follow-up.

        Exclusion Criteria:

          -  Female participant who is pregnant, lactating or planning pregnancy during the course
             of the study.

          -  Presence of any condition which in the judgment of the investigator would place the
             participant at undue risk or interfere with the results of the study (e.g. serious
             underlying cardiac, renal, hepatic or neurological disease; severe malnutrition;
             congenital defects or febrile condition).

          -  Hepatitis B surface antigen (HBsAg) detected in serum.

          -  Screening ECG demonstrates a QTc interval ≥ 450 ms

          -  Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless has taken
             part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior
             to participation in that study, and negative HCV RNA PCR at screening for this study).

          -  Anaemia (Hb < 10 g/dL)

          -  Positive malaria parasitaemia at screening or baseline (Month 0, Day 0).

          -  Use of any investigational or non-registered product or investigational use of a
             registered product (drug or vaccine), other than the study vaccines, during the period
             from the date of screening to the first vaccination, or planned use during the study
             period.

          -  Any medical condition that in the judgment of the investigator would make
             intramuscular (IM) injection unsafe.

          -  Any medical condition that in the judgment of the investigator would make the
             administration of the antimalarial treatment unsafe, such as prior allergic reactions
             to one or more component of the drug regimen: artemisinins, piperaquine or primaquine.

          -  Contraindications to the use of artemisinins, piperaquine or primaquine or use of
             medications known to have a potentially clinically significant interaction with these
             medications.

          -  Chronic administration (defined as more than 14 days in total) of immunosuppressants
             or other immune-modifying drugs during the period starting six months prior to the
             first vaccine dose. For corticosteroids, this will mean prednisone > 20 mg/day (for
             adult subjects), or equivalent. Inhaled and topical steroids are allowed.

          -  Planned administration/administration of a vaccine not foreseen by the study protocol
             in the period starting seven days before the first dose.

          -  Concurrently participating in another clinical study, at any time during the study
             period, in which the subject has been or will be exposed to an investigational or a
             non-investigational vaccine/product.

          -  History of splenectomy.

          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, including
             HIV infection or based on medical history and physical examination.

          -  History of anaphylaxis post-vaccination.

          -  Serious chronic illness.

          -  Any abnormal baseline laboratory screening tests: ALT, AST, creatinine, haemoglobin,
             platelet count, total WBC, out of normal range as defined in the protocol.

          -  Hepatomegaly, right upper quadrant abdominal pain or tenderness.

          -  Personal history of autoimmune disease.

          -  Administration of immunoglobulins and/or any blood products during the period starting
             three months before the first dose of study vaccine or planned administration during
             the study period.