Pfs230D1M-EPA/AS01 Vaccine, a Transmission Blocking Vaccine Against Plasmodium Falciparum, in an Age De-Escalation Trial of Children and a Family Compound Trial in Mali
Condition: Malaria
MeSH terms: Malaria
Intervention: Pfs230D1M-EPA/AS01; HAVRIX; TYPHIM Vi (Salmonella typhi vaccine); Menactra; AVAXIM
Intervention description: The Pfs230D1M-EPA was formulated as conjugated Pfs230D1M in 4 mM phosphate-buffered saline (PBS) to a 2X dilution of the high dose (160 (Micro)g/mL in 0.5 mL volume) in cGMP compliance at Walter Reed Bioproduction facility in April 2016 and will be provided as a single use vial. AS01B adjuvant was manufactured for use in the SHINGRIX vaccine by GSK; HAVRIX (Hepatitis A Vaccine; HAV) is produced by GSK and is a sterile suspension of inactivated virus for IM administration. The virus (strain HM175) is propagated in MRC-5 human diploid cells. HAVRIX is FDA approved for active immunization against disease caused by HAV for persons 12 months of age and older.; TYPHIM Vi (Typhoid Vi Polysaccharide Vaccine), produced by Sanofi Pasteur SA, for IM use, is a sterile solution containing the cell surface Vi polysaccharide extracted from Salmonella enterica serovar Typhi, S typhi Ty2 strain (inactivated, subunit vaccine). TYPHIM Vi vaccine is indicated for active immunization for the prevention of typhoid fever caused by S typhi and is FDA approved for use in persons 2 years of age or older; Menactra (Sanofi Pasteur) is a sterile, intramuscularly administered vaccine that contains Neisseria meningitidis serogroup A, C, Y, and W-135 capsular polysaccharide antigens individually conjugated to diphtheria toxoid protein. No preservative or adjuvant is added during the manufacturing process. Menactra is FDA approved for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y, and W-135 (but does not protect against serotype B) for use in individuals 9 months through 55 years of age.; AVAXIM - Pediatric [Hepatitis A Vaccine Inactivated] is a sterile, whitish, cloudy suspension. The active ingredient is a purified and formaldehyde-inactivated hepatitis A virus (HAV) obtained from the GBM strain, cultured on MRC-5 human diploid cells. HAV is adsorbed onto aluminum.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1301.0
Sex: All
Minimum age: 1 Year
Healthy volunteers: No
Keywords: Randomized; Assays; Blood Smear; Antibody; Parasites

Summary:

      Background:

      Malaria affects many people in Mali and other parts of Africa. It is spread by mosquito
      bites. Malaria can make people sick or can lead to death. Scientists want to learn if a
      vaccine can stop it from spreading to other people.

      Objective:

      To test how well an experimental malaria vaccine works to decrease malaria infections.

      Eligibility:

      Healthy people ages 5 and older who live in Doneguebougou, Mali, and surrounding areas

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Blood, urine, and heart tests

      EKG

      Participants will be randomly assigned to get either the experimental vaccine or an approved
      vaccine. They will not know which they are getting.

      Participants will have a visit about a week before their first vaccine. They will take a
      medicine that kills malaria. They will take it at the clinic the next 2 days. Participants
      ages 5-8 will take the drug again 2 weeks before their third vaccine.

      Participants get the vaccine through a needle in the arm. They will have visits 1, 3, 7, and
      14 days after. They will have blood tests or finger pricks.

      Participants will get another vaccine 1 and 6 months later.

      Participants will have blood tests once a month. At these visits they may also have urines
      tests or mosquito feeds. For the feeds a cup full of mosquitoes will be placed on arms or
      legs for 15-20 minutes.

      Participants will have visits twice a month for 4 months after their last vaccine.
    

Eligibility criteria:

        -  INCLUSION CRITERIA FOR GROUPS 1,2,3:

        All of the following criteria must be fulfilled for a volunteer to participate in this
        trial:

          1. Meets age requirements for Arm currently being enrolled.

          2. Available for the duration of the trial.

          3. Family compound known resident or long-term resident (more than 1 year) of
             Doneguebougou, Mali or surrounding villages.

          4. Able to provide proof of identity to the satisfaction of the study clinician
             completing the enrollment process.

          5. In good general health and without clinically significant medical history in the
             opinion of the investigator.

          6. Females of childbearing potential must be willing to use reliable contraception from
             21 days prior to Study Day 0 and until 1 month after the last vaccination.

               -  A reliable method of birth control includes one of the following:

          1. Confirmed pharmacologic contraceptives (parenteral) delivery;

          2. Intrauterine or implantable device

        EXCEPTIONS to required pregnancy prevention includes the following:

          1. Postmenopausal state: defined as no menses for 12 months without an alternative
             medical cause

          2. Surgical sterilization

          3. Unmarried AND not sexually active AND menstruating OR not menstruating females 12-17
             years of age

          4. NOTE: if a female of childbearing potential s status changes during the course of
             vaccination through 1 month post vaccination (e.g. they become >=18 years of age,
             married, or sexually active), the female will be required to start reliable
             contraception

        7. Willing to have blood samples stored for future research.

        INCLUSION CRITERIA FOR GROUP 4:

        All of the following criteria must be fulfilled for a volunteer to participate in this
        trial:

          1. Meets age requirements for Arm currently being enrolled.

          2. Available for the duration of the trial.

          3. Family compound known resident or long-term resident (more than 1 year) of
             Doneguebougou, Mali or surrounding villages.

          4. Able to provide proof of identity to the satisfaction of the study clinician
             completing the enrollment process.

          5. In good general health and without clinically significant medical history in the
             opinion of the investigator.

          6. Willing to have blood samples stored for future research.

        Inclusion Criteria for Groups 1, 2, 3, (Year 2)

        All of the following criteria must be fulfilled for a volunteer to continue to participate
        in this trial:

        1. Previously enrolled in the study and has received at least 1 vaccination. 2. Available
        for the duration of the trial.

        3. In good general health and without clinically significant medical history in the opinion
        of the investigator.

        4. Females of childbearing potential must be willing to use reliable contraception from 21
        days prior to scheduled vaccine dose #4 and until 1 month after the 4th vaccination.

        -A reliable method of birth control includes one of the following:

          1. Confirmed pharmacologic contraceptives (parenteral) delivery;

          2. Intrauterine or implantable device

        EXCEPTIONS to required pregnancy prevention includes the following:

          1. Postmenopausal state: defined as no menses for 12 months without an alternative
             medical cause

          2. Surgical sterilization

          3. Unmarried AND not sexually active AND menstruatingOR not menstruating females 12-17
             years of age

          4. NOTE: if a female of childbearing potential s status changes during the course of
             vaccination through 1 month post vaccination (e.g. they become greater than or equal
             to 18 years of age, married, or sexually active), the female will be required to start
             reliable contraception

          5. Willing to have blood samples stored for future research.

        Inclusion Criteria for Group 4 (Year 2):

        All of the following criteria must be fulfilled for a volunteer to continue to participate
        in this trial:

          1. Previously enrolled in the study

          2. Available for the duration of the trial.

          3. In good general health and without clinically significant medical history in the
             opinion of the investigator.

          4. Willing to have blood samples stored for future research.

        EXCLUSION CRITERIA FOR GROUPS 1, 2, 3:

        An individual will be excluded from participating in this trial if any one of the following
        criteria is fulfilled:

          1. Pregnant, as determined by a positive urine or serum beta human choriogonadotropin
             (beta-hCG) test (if female).

             NOTE: Pregnancy is also a criterion for discontinuation of any further vaccine dosing

          2. Menstruating females 11 years of age and younger. (In order to avoid cultural
             implications of further assessing pregnancy potential i.e. sexual activity in this age
             group.)

          3. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator
             affects the ability of the subject to understand and comply with the study protocol at
             a level appropriate for the subject s age.

          4. Hemoglobin, white blood cell (WBC), absolute neutrophil count, or platelet levels
             outside the local laboratory defined limits of normal. (Subjects may be included at
             the investigator s discretion for not clinically significant values outside of normal
             range and <= Grade 2.)

          5. Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory defined
             upper limit of normal. (Subjects may be included at the investigator s discretion for
             not clinically significant values outside of normal range and <= Grade 2.)

          6. Infected with HIV

          7. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine,
             rheumatologic, autoimmune, hematological, oncologic, or renal disease by history,
             physical examination, and/or laboratory studies including urinalysis.

          8. Clinically significant prolonged QTc (>450 milliseconds) on screening EKG

          9. History of receiving any investigational product within the past 30 days.

         10. Current or planned participation in an investigational vaccine study until the last
             required protocol visit.

         11. Medical, occupational, or family problems as a result of alcohol or illicit drug use
             during the past 12 months.

         12. History of a severe allergic reaction or anaphylaxis.

         13. Known:

               -  Severe asthma, defined as asthma that is unstable or required emergent care,
                  urgent care, hospitalization, or intubation during the past 2 years, or that has
                  required the use of oral or parenteral corticosteroids at any time during the
                  past 2 years.

               -  Autoimmune or antibody-mediated disease including but not limited to: systemic
                  lupus erythematosus, rheumatoid arthritis, multiple sclerosis,
                  Sj(SqrRoot)(Delta)gren s syndrome, or autoimmune thrombocytopenia.

               -  Immunodeficiency syndrome.

               -  Seizure disorder (exception: history of simple febrile seizures)

               -  Asplenia or functional asplenia.

               -  Use of chronic (>=14 days) oral or intravenous (IV) corticosteroids (excluding
                  topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or
                  immunosuppressive drugs within 30 days of Study Day 0.

               -  Allergy to latex or neomycin

               -  Adverse reaction to hepatitis A and/or typhoid and/or meningococcal vaccine in
                  the past

               -  Adverse reaction to artemether/lumefantrine in the past

         14. Receipt of:

             -Live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks to
             enrollment.

               -  Immunoglobulins and/or blood products within the past 6 months.

               -  Investigational malaria vaccine in the last 2 years.

         15. Any other condition that in the opinion of the investigator would jeopardize the
             safety or rights of a subject participating in the trial, interfere with the
             evaluation of the study objectives, or would render the subject unable to comply with
             the protocol.

        Co-enrollment guidelines: Co-enrollment in other trials is restricted, other than
        enrollment on observational studies. Consideration for co-enrollment in trials evaluating
        the use of a licensed medication will require the approval of the PI. Study staff should be
        notified of co-enrollment on any other protocol as it may require the approval of the
        investigator.

        Exclusion Criteria for Group 4:

        An individual will be excluded from participating in this trial if any one of the following
        criteria is fulfilled:

          1. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator
             affects the ability of the subject to understand and comply with the study protocol at
             a level appropriate for the subject s age.

          2. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine,
             rheumatologic, autoimmune, hematological, oncologic, or renal disease by history,
             physical examination, and/or laboratory studies including urinalysis.

          3. Clinically significant prolonged QTc (by sex/age) on screening EKG

          4. History of adverse reactions to artemether/lumefantrine in the past

          5. History of receiving any investigational product within the past 30 days.

          6. Current or planned participation in an investigational vaccine study until the last
             required protocol visit.

          7. Receipt of:

             -Investigational malaria vaccine in the last 2 years.

          8. Any other condition that in the opinion of the investigator would jeopardize the
             safety or rights of a subject participating in the trial, interfere with the
             evaluation of the study objectives, or would render the subject unable to comply with
             the protocol.

        Exclusion Criteria for Groups 1, 2, 3 (Year 2):

        An individual will be excluded from participating in this trial if any one of the following
        criteria is fulfilled:

          1. Pregnant, as determined by a positive urine or serum beta human choriogonadotropin
             (beta-hCG) test (if female).

             NOTE: Pregnancy is also a criterion for discontinuation of any further vaccine dosing

          2. Menstruating females 11 years of age and younger. (In order to avoid cultural
             implications of further assessing pregnancy potential i.e. sexual activity in this age
             group.)

          3. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator
             affects the ability of the subject to understand and comply with the study protocol at
             a level appropriate for the subject s age.

          4. Hemoglobin, white blood cell (WBC), absolute neutrophil count, or platelet levels
             outside the local laboratory defined limits of normal. (Subjects may be included at
             the investigator s discretion for not clinically significant values outside of normal
             range and less than or equal to Grade 2.)

          5. Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory defined
             upper limit of normal. (Subjects may be included at the investigator s discretion for
             not clinically significant values outside of normal range and less than or equal to
             Grade 2.)

          6. Infected with HIV

          7. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine,
             rheumatologic, autoimmune, hematological, oncologic, or renal disease by history,
             physical examination, and/or laboratory studies including urinalysis.

          8. History of receiving any investigational product within the past 30 days.

          9. Medical, occupational, or family problems as a result of alcohol or illicit drug use
             during the past 12 months.

         10. History of a severe allergic reaction or anaphylaxis.

         11. Known:

             -Severe asthma, defined as asthma that is unstable or required emergent care, urgent
             care, hospitalization, or intubation during the past 2 years, or that has required the
             use of oral or parenteral corticosteroids at any time during the past 2 years.

             -Autoimmune or antibody-mediated disease including but not limited to: systemic lupus
             erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren s syndrome, or
             autoimmune thrombocytopenia.

               -  Immunodeficiency syndrome.

               -  Seizure disorder (exception: history of simple febrile seizures)

               -  Asplenia or functional asplenia.

               -  Use of chronic (greater than or equal to 14 days) oral or intravenous (IV)
                  corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e.,
                  prednisone >10 mg/day) or immunosuppressive drugs within 30 days of Study Day 0.

               -  Allergy to latex or neomycin

               -  Adverse reaction to hepatitis A and/or typhoid and/or meningococcal vaccine in
                  the past

               -  Adverse reaction to artemether/lumefantrine in the past

         12. Receipt of:

               -  Live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks
                  to enrollment.

               -  Immunoglobulins and/or blood products within the past 6 months.

         13. Any other condition that in the opinion of the investigator would jeopardize the
             safety or rights of a subject participating in the trial, interfere with the
             evaluation of the study objectives, or would render the subject unable to comply with
             the protocol.

        Exclusion Criteria for Group 4 (Year 2):

        An individual will be excluded from participating in this trial if any one of the following
        criteria is fulfilled:

        1. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator
        affects the ability of the subject to understand and comply with the study protocol at a
        level appropriate for the subject s age.

        2. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine,
        rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical
        examination, and/or laboratory studies including urinalysis.

        3. History of adverse reactions to artemether/lumefantrine in the past

        4. History of receiving any investigational product within the past 30 days.

        5. Current or planned participation in an investigational vaccine study until the last
        required protocol visit.

        6. Receipt of:

          -  Investigational malaria vaccine in the last 2 years.

             7. Any other condition that in the opinion of the investigator would jeopardize the
             safety or rights of a subject participating in the trial, interfere with the
             evaluation of the study objectives, or would render the subject unable to comply with
             the protocol.