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Safety, Tolerability and Efficacy of PfSPZ Vaccine in Healthy Children and Infants 5 Months - 9 Years Living in Kenya

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Sanaria Inc.
Sponsor:
Collaborators:
Kenya Medical Research Institute
Centers for Disease Control and Prevention
National Institutes of Health (NIH)
University of Maryland
Information provided by (Responsible Party):
Sanaria Inc.
ClinicalTrials.gov Identifier:
NCT02687373
First received: February 9, 2016
Last updated: July 20, 2016
Last verified: July 2016
  Purpose
This study will be conducted in Siaya County in Nyanza Province, western Kenya. Healthy children aged 5 months through 9 years of age living within approximately 10 km of the study clinic(s) (Siaya County Referral Hospital, or Wagai dispensary, a government health facility in Wagai division) will be eligible for participation in Part 1; healthy infants aged 5 months - 12 months inclusive will be eligible for Part 2.

Condition Intervention Phase
Malaria
Biological: PfSPZ Vaccine
Other: Normal Saline
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Safety, Tolerability and Efficacy of PfSPZ Vaccine Administered by Direct Venous Inoculation (DVI) to Healthy Children and Infants 5 Months Through 9 Years of Age Living in an Area of High Malaria Transmission in Western Kenya: Age De-escalation and Dose Escalation and a Double Blind, Randomized Placebo-Controlled Trial for Safety and Efficacy

Resource links provided by NLM:


Further study details as provided by Sanaria Inc.:

Primary Outcome Measures:
  • Part 1 - Incidence and type of adverse events (AE) [ Time Frame: Collected from day of each vaccination until day 28 post vaccination ]
    Incidence and type of solicited and unsolicited adverse events including breakthrough malaria infections and clinical laboratory assessments (hematological, liver and renal function) will be collected within 28 days after each vaccination. Proportions of participants with AEs and frequencies of individual AEs will be calculated and compared against participants in the same age category and dose group receiving placebo.

  • Part 1 - Incidence and type of possibly/probably or definitely related serious adverse events (SAEs) [ Time Frame: Collected from day of first vaccination until close out visit (28 days for 3 lower doses, 84 days for 2 higher doses) ]
    Incidence of all hospitalizations, deaths, disabilities caused by at least possibly related SAEs during study participation

  • Part 1 - Assessment of Pf-specific antibodies in the different age categories and to the different vaccine doses [ Time Frame: Collected 1 week after each vaccination ]
    Collection of blood samples for antibodies on day 8 after each vaccination. Following vaccination serum will be taken and an assessment of Plasmodium falciparum (Pf)f-specific antibodies against specific malaria proteins such as the circumsporozoite protein (CSP) PfCSP and whole Pf sporozoites (SPZ) will be determined by enzyme-linked immunosorbent assay (ELISA) and automated immunofluorescence assay (aIFA) respectively.

  • Part 2 - Incidence and type of adverse events in infants 5-12 months of age following administration of PfSPZ Vaccine [ Time Frame: Collected from day of each vaccination until day 28 post vaccination ]
    Incidence and type of solicited and unsolicited adverse events including breakthrough malaria infections and clinical laboratory assessments (hematological, liver and renal function) will be collected during 28 days after each vaccination.

  • Part 2 - Incidence and type of possibly/probably or definitely related serious adverse events (SAEs) following administration of PfSPZ Vaccine [ Time Frame: Collected from day of first vaccination through the 12-month follow-up period. ]
    Incidence of all hospitalizations, deaths, disabilities caused by at least possibly related to the study product during the 12-month follow-up period.

  • Part 2 - Assessment of Pf-specific antibodies in infants of 5-12 months to three vaccinations of PfSPZ Vaccine [ Time Frame: Collected 1 week after the first and second vaccination and 2 weeks after the third vaccination. ]
    Collection of blood samples for antibodies on day 8 after vaccination 1 and 2 and day 15 after the third PfSPZ vaccination. Following vaccination serum will be taken and an assessment of Plasmodium falciparum (Pf)f-specific antibodies against specific malaria proteins such as the circumsporozoite protein (CSP) PfCSP and whole Pf sporozoites (SPZ) will be determined by enzyme-linked immunosorbent assay (ELISA) and automated immunofluorescence assay (aIFA) respectively.

  • Part 2 - Ratio of Pf positive blood smear (+BS) in experimental arm to Pf +BS in placebo arm to determine efficacy of PfSPZ Vaccine during 6 months after last dose [ Time Frame: 2 weeks to 6 months after the last vaccine dose ]
    Efficacy against malaria infection of PfSPZ Vaccine administered to infants 5-12 months of age in 3 doses by passive and active surveillance for naturally acquired Pf infection, measured by blood smear microscopy, during 6 months following the last vaccine dose.


Secondary Outcome Measures:
  • Part 2 - Ratio of Pf +BS in experimental arm to Pf +BS in placebo arm to determine efficacy of PfSPZ Vaccine during 12 months after last dose [ Time Frame: 2 weeks to 12 months after the last vaccine dose ]
    Efficacy against malaria of PfSPZ Vaccine administered to infants 5-12 months of age in 3 doses by passive and active surveillance for naturally acquired Pf infection, measured by blood smear microscopy, during 12 months following the last vaccine dose will be performed and the prevalence ratio of the prevalence of malaria infection by blood smear between each dose study arm and placebo will be compared.

  • Part 2 - Ratio of Pf positive PCR in experimental arm to Pf positive PCR in placebo arm to determine efficacy against submicroscopic malaria infection of PfSPZ Vaccine following 6 and 12 months after the last dose [ Time Frame: 2 weeks to 6 and 12 months after the last vaccine dose ]
    Efficacy against submicroscopic malaria infection of PfSPZ Vaccine administered to infants 5-12 months of age in 3 doses by passive and active surveillance for naturally acquired Pf infection, measured by PCR, during 6 and 12 months following the last vaccine dose.

  • Part 2 - Assessment of Pf-specific antibodies, parasite-specific T cell responses and RNA sequencing. [ Time Frame: Before the first vaccination, 1 week after vaccination 1 and 2, 2 weeks after vaccination 3 and at 6 months and 12 months after the last vaccination ]
    Collection of blood samples for Anti PfSPZ antibodies and RNA sequencing at different time points. Following vaccination serum will be taken and an assessment of Plasmodium falciparum (Pf)f-specific antibodies against specific malaria proteins such as the circumsporozoite protein (CSP) PfCSP and whole Pf sporozoites (SPZ) will be determined by enzyme-linked immunosorbent assay (ELISA) and automated immunofluorescence assay (aIFA). For assessment of parasite-specific T cell responses, PBMCs will be assessed by multi-parameter flow cytometry and / or ELISPOT, and intracellular cytokine staining. RNA sequencing from whole blood will be performed by processing the RNA and performing deep sequencing. Analysis of gene expression will be performed to develop biomarkers and predictors of protection.

  • Part 2 - Assessment of Pf-specific antibodies, parasite-specific T cell responses and RNA sequencing to determine correlation of immune response with efficacy [ Time Frame: Entire study period ]
    Comparison of the immune response at different time points and the protection against naturally acquired Pf infection. Following vaccination serum will be taken and an assessment of Plasmodium falciparum (Pf)f-specific antibodies against specific malaria proteins such as the circumsporozoite protein (CSP) PfCSP and whole Pf sporozoites (SPZ) will be determined by enzyme-linked immunosorbent assay (ELISA) and automated immunofluorescence assay (aIFA). For assessment of parasite-specific T cell responses, PBMCs will be assessed by multi-parameter flow cytometry and / or ELISPOT, and intracellular cytokine staining. RNA sequencing from whole blood will be performed by processing the RNA and performing deep sequencing. Analysis of gene expression will be performed to develop biomarkers and predictors of protection.


Other Outcome Measures:
  • Ratio of Pf +BS in experimental arm to Pf +BS in placebo arm to determine efficacy against Pf infection at certain parasite thresholds in each study arm [ Time Frame: 2 weeks to 12 months after last vaccination ]
    Passive and active surveillance for naturally acquired Pf infection, measured by blood smear microscopy, during 12 months following the last dose in each study arm will be performed and the Pf infection by blood smear at parasite density >400 or >5000 parasites per microliter between each dose study arm and placebo will be compared.

  • Ratio of Pf +BS in experimental arm to Pf +BS in placebo arm to determine efficacy against clinical malaria and malaria hospitalization in each study arm [ Time Frame: 2 weeks to 12 months after last vaccination ]
    Passive and active surveillance for naturally acquired Pf infection of > 5000 parasites per microliter measured by blood smear microscopy associated with fever (clinical malaria) and/or hospitalization as well as hospitalization for severe malarial anemia, during 12 months following the last dose in each study arm will be performed and each study arm will be compared with the placebo group.

  • Effect of vaccination on anemia [ Time Frame: 6 months and 12 months after last vaccination ]
    Measure hemoglobin at 6 months and 12 months after the last vaccination and compare hemoglobin levels in each study arm with the placebo group.


Estimated Enrollment: 572
Study Start Date: July 2016
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: Grp 1A - PfSPZ Vaccine

Children aged 5-9 years (inclusive) of age will be enrolled in this group.

N=8; Dose of 4.5 x 10^5 PfSPZ Vaccine administered DVI, as a single vaccination.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 1: Grp 1A - Normal Saline

Children aged 5-9 years (inclusive) of age will be enrolled in this group.

N=4; Normal saline administered DVI, as a single vaccination.

Other: Normal Saline
0.9% Sodium chloride
Experimental: Part 1: Grp 1B - PfSPZ Vaccine

Children aged 5-9 years (inclusive) of age will be enrolled in this group.

N=8; Two doses of 9.0 x 10^5 PfSPZ Vaccine administered DVI, 8 weeks apart. The 1st dose will be administered 2 weeks after Grp 1A dose has been shown to be well-tolerated and without safety concerns. The 2nd dose will be administered 8 weeks after the 1st dose in this group does not show any safety signals.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 1: Grp 1B - Normal Saline

Children aged 5-9 years (inclusive) of age will be enrolled in this group.

N=4; Two doses of normal saline administered DVI, 8 weeks apart. The 1st dose will be administered 2 weeks after Grp 1A dose has been shown to be well-tolerated and without safety concerns. The 2nd dose will be administered 8 weeks after the 1st dose in this group does not show any safety signals.

Other: Normal Saline
0.9% Sodium chloride
Experimental: Part 1: Grp 1C - PfSPZ Vaccine

Children aged 5-9 years (inclusive) of age will be enrolled in this group.

N=8; Two doses of 1.8 x 10^6 PfSPZ Vaccine administered DVI, 8 weeks apart. The 1st dose will be administered 2 weeks after the 1st dose of Grp 1B has been shown to be well-tolerated and without safety concerns. The 2nd dose will be administered 8 weeks after the 1st dose in this group does not show any safety signals.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 1: Grp 1C - Normal Saline

Children aged 5-9 years (inclusive) of age will be enrolled in this group.

N=4; Two doses of normal saline administered DVI, 8 weeks apart. The 1st dose will be administered after the 1st dose of Grp 1B has been shown to be well-tolerated and without safety concerns. The 2nd dose will be administered 8 weeks after the 1st dose in this group does not show any safety signals.

Other: Normal Saline
0.9% Sodium chloride
Experimental: Part 1: Grp 2A - PfSPZ Vaccine

Children aged 13-59 months (inclusive) of age will be enrolled in this group.

N=8; Dose of 1.35 x 10^5 PfSPZ Vaccine administered DVI, as a single vaccination. This dose will be administered 2 weeks after the 1st dose of Grp 1B has been shown to be well-tolerated and without safety concerns.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 1: Grp 2A - Normal Saline

Children aged 13-59 months (inclusive) of age will be enrolled in this group.

N=4; Normal saline administered DVI, as a single vaccination. This dose will be administered 2 weeks after the 1st dose of Grp 1B has been shown to be well-tolerated and without safety concerns.

Other: Normal Saline
0.9% Sodium chloride
Experimental: Part 1: Grp 2B - PfSPZ Vaccine

Children aged 13-59 months (inclusive) of age will be enrolled in this group.

N=8; Dose of 2.7 x 10^5 PfSPZ Vaccine administered DVI, as a single vaccination. This dose will be administered 2 weeks after Grp 2A has been shown to be well-tolerated and without safety concerns.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 1: Grp 2B - Normal Saline

Children aged 13-59 months (inclusive) of age will be enrolled in this group.

N=4; Normal saline administered DVI, as a single vaccination. This dose will be administered 2 weeks after Grp 2A has been shown to be well-tolerated and without safety concerns.

Other: Normal Saline
0.9% Sodium chloride
Experimental: Part 1: Grp 2C - PfSPZ Vaccine

Children aged 13-59 months (inclusive) of age will be enrolled in this group.

N=8; Dose of 4.5 x 10^5 PfSPZ Vaccine administered DVI, as a single vaccination. This dose will be administered 2 weeks after Grp 2B has been shown to be well-tolerated and without safety concerns.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 1: Grp 2C - Normal Saline

Children aged 13-59 months (inclusive) of age will be enrolled in this group.

N=4; Normal saline administered DVI, as a single vaccination. This dose will be administered 2 weeks after Grp 2B has been shown to be well-tolerated and without safety concerns.

Other: Normal Saline
0.9% Sodium chloride
Experimental: Part 1: Grp 2D - PfSPZ Vaccine

Children aged 13-59 months (inclusive) of age will be enrolled in this group.

N=8; Two doses of 9.0 x 10^5 PfSPZ Vaccine administered DVI, 8 weeks apart. The 1st dose will be administered 2 weeks after Grp 2C has been shown to be well-tolerated and without safety concerns. The 2nd dose will be administered 8 weeks after the 1st dose in this group does not show any safety signals.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 1: Grp 2D - Normal Saline

Children aged 13-59 months (inclusive) of age will be enrolled in this group.

N=4; Two doses of normal saline administered DVI, 8 weeks apart. The 1st dose will be administered 2 weeks after Grp 2C has been shown to be well-tolerated and without safety concerns. The 2nd dose will be administered 8 weeks after the 1st dose in this group does not show any safety signals.

Other: Normal Saline
0.9% Sodium chloride
Experimental: Part 1: Grp 2E - PfSPZ Vaccine

Children aged 13-59 months (inclusive) of age will be enrolled in this group.

N=8; Two doses of 1.8 x 10^6 PfSPZ Vaccine administered DVI, 8 weeks apart. The 1st dose will be administered 2 weeks after Grp 2D has been shown to be well-tolerated and without safety concerns. The 2nd dose will be administered 8 weeks after the 1st dose in this group does not show any safety signals.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 1: Grp 2E - Normal Saline

Children aged 13-59 months (inclusive) of age will be enrolled in this group.

N=4; Two doses of normal saline administered DVI, 8 weeks apart. The 1st dose will be administered 2 weeks after Grp 2D has been shown to be well-tolerated and without safety concerns. The 2nd dose will be administered 8 weeks after the 1st dose in this group does not show any safety signals.

Other: Normal Saline
0.9% Sodium chloride
Experimental: Part 1: Grp 3A - PfSPZ Vaccine

Children aged 5-12 months (inclusive) of age will be enrolled in this group.

N=8; Dose of 1.35 x 10^5 PfSPZ Vaccine administered DVI, as a single vaccination. This dose will be administered 2 weeks after Grp 2B has been shown to be well-tolerated and without safety concerns.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 1: Grp 3A - Normal Saline

Children aged 5-12 months (inclusive) of age will be enrolled in this group.

N=4; Normal saline administered DVI, as a single vaccination. This dose will be administered 2 weeks after Grp 2B has been shown to be well-tolerated and without safety concerns.

Other: Normal Saline
0.9% Sodium chloride
Experimental: Part 1: Grp 3B - PfSPZ Vaccine

Children aged 5-12 months (inclusive) of age will be enrolled in this group.

N=8; Dose of 2.7 x 10^5 PfSPZ Vaccine administered DVI, as a single vaccination. This dose will be administered 2 weeks after Grp 3A has been shown to be well-tolerated and without safety concerns.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 1: Grp 3B - Normal Saline

Children aged 5-12 months (inclusive) of age will be enrolled in this group.

N=4; Normal saline administered DVI, as a single vaccination. This dose will be administered 2 weeks after Grp 3A has been shown to be well-tolerated and without safety concerns.

Other: Normal Saline
0.9% Sodium chloride
Experimental: Part 1: Grp 3C - PfSPZ Vaccine

Children aged 5-12 months (inclusive) of age will be enrolled in this group.

N=8; Dose of 4.5 x 10^5 PfSPZ Vaccine administered DVI, as a single vaccination. This dose will be administered 2 weeks after Grp 3B has been shown to be well-tolerated and without safety concerns.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 1: Grp 3C - Normal Saline

Children aged 5-12 months (inclusive) of age will be enrolled in this group.

N=4; Normal saline administered DVI, as a single vaccination. This dose will be administered 2 weeks after Grp 3B has been shown to be well-tolerated and without safety concerns.

Other: Normal Saline
0.9% Sodium chloride
Experimental: Part 1: Grp 3D - PfSPZ Vaccine

Children aged 5-12 months (inclusive) of age will be enrolled in this group.

N=8; Two doses of 9.0 x 10^5 PfSPZ Vaccine administered DVI, 8 weeks apart. The 1st dose will be administered 2 weeks after Grp 3C has been shown to be well-tolerated and without safety concerns. The 2nd dose will be administered 8 weeks after the 1st dose in this group does not show any safety signals.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 1: Grp 3D - Normal Saline

Children aged 5-12 months (inclusive) of age will be enrolled in this group.

N=4; Two doses of normal saline administered DVI, 8 weeks apart. The 1st dose will be administered 2 weeks after Grp 3C has been shown to be well-tolerated and without safety concerns. The 2nd dose will be administered 8 weeks after the 1st dose in this group does not show any safety signals.

Other: Normal Saline
0.9% Sodium chloride
Experimental: Part 1: Grp 3E - PfSPZ Vaccine

Children aged 5-12 months (inclusive) of age will be enrolled in this group.

N=8; Two doses of 1.8 x 10^6 PfSPZ Vaccine administered DVI, 8 weeks apart. The 1st dose will be administered 2 weeks after Grp 3D has been shown to be well-tolerated and without safety concerns. The 2nd dose will be administered 8 weeks after the 1st dose in this group does not show any safety signals.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 1: Grp 3E - Normal Saline

Children aged 5-12 months (inclusive) of age will be enrolled in this group.

N=4; Two doses of normal saline administered DVI, 8 weeks apart. The 1st dose will be administered 2 weeks after Grp 3D has been shown to be well-tolerated and without safety concerns. The 2nd dose will be administered 8 weeks after the 1st dose in this group does not show any safety signals.

Other: Normal Saline
0.9% Sodium chloride
Experimental: Part 2: Group 1 - PfSPZ Vaccine

Infants aged 5-12 months (inclusive) of age at vaccination will be enrolled in Part 2.

N=104; the highest dose that is determined to be safe and well tolerated in the Part 1 trial, administered in 3 doses by DVI at 0, 8 and 16 weeks. Likely dosage will be 1.8 x 10^6 PfSPZ per dose.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Experimental: Part 2: Group 2 - PfSPZ Vaccine

Infants aged 5-12 months (inclusive) of age at vaccination will be enrolled in Part 2.

N=104; the second highest dose, which is half of the highest dose, administered in 3 doses by DVI at 0, 8 and 16 weeks. Likely dosage will be 9.0 x 10^5 PfSPZ per dose.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Experimental: Part 2: Group 3 - PfSPZ Vaccine

Infants aged 5-12 months (inclusive) of age at vaccination will be enrolled in Part 2.

N=104; a lower dose (half of the second highest dose) administered in 3 doses by DVI at 0, 8, 16 weeks. Likely dosage will be 4.5x 10^5 PfSPZ per dose.

Biological: PfSPZ Vaccine
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Placebo Comparator: Part 2: Group 4 - Normal Saline

Infants aged 5-12 months (inclusive) of age at vaccination will be enrolled in Part 2.

N=104; a placebo arm, will receive normal saline by DVI, 3 times at 8 week intervals.

Other: Normal Saline
0.9% Sodium chloride

Detailed Description:

Part 1: Age De-Escalation and Dose Escalation Part 1 of this trial is a randomized blinded evaluation of the safety and tolerability of PfSPZ Vaccine administered by DVI in healthy children and infants living in an area of high malaria transmission. A maximum of 156 children from 5 months to 9 years inclusive at vaccination will be enrolled and randomized to receive vaccine or normal saline (NS) placebo by DVI. Total participation time in the dose escalation trial ranges from 5-16 weeks per participant from screening visit to close out or 4 - 12 weeks from enrolment to close out.

Vaccination will begin in the 5-9 year age group at a dosage of 4.5 x10^5 PfSPZ. A single vaccination will be administered by DVI to each of 12 participants aged 5-9 years (inclusive) of age, 8 receiving PfSPZ vaccine and 4 participants receiving NS placebo by DVI, with treatment allocation randomized and double-blind. Once the initial dose has been shown to be well tolerated and without safety concerns, the next higher dose of 9.0 x 10^5 PfSPZ will be administered to a second group of 5-9 year olds. Once this has been shown to be well tolerated and without safety concerns, the highest dose of 1.8 x 10^6 PfSPZ will be given to a third group of 5-9 year olds and concurrently the lowest dose (1.35 x10^5) will be given to a same-sized group of younger children aged 13-59 months. Two weeks later, this dose will be escalated to 2.7 x10^5 PfSPZ in a second group of children aged 13-59 months. Only once this dose is shown to be well-tolerated and without safety concerns will PfSPZ Vaccine, at the lowest dose, be given to infants aged 5 - 12 months. Within each age group, dosages will increase stepwise until they reach 1.8 x 10^6 PfSPZ, with the initiation of each group staggered by at least 2 weeks, provided that no safety thresholds are surpassed. In each dosage level, the PfSPZ Vaccine or placebo will be provided to a limited number of participants each day (e.g. 3 participants from one age group on days 1 through 4). The PfSPZ Vaccine dose will only be increased to the next dose level when safety has been assessed in subjects of the first group. The same procedures will be followed for all doses. Children in all age groups who are enrolled to receive the 2 highest doses, i.e. 9.0 x 10^5 or 1.8 x 10^6 PfSPZ, or placebo, will receive a second vaccination of the same dose after 8 weeks, provided the first vaccination at this dose level did not show safety signals.

Part 2: Safety and Efficacy Part of this study will be conducted in the outpatient areas of Siaya County Referral Hospital, a large referral hospital in western Kenya and in Wagai dispensary. A maximum of 416 infants from 5 M to 12 M inclusive at vaccination will be enrolled into this safety and efficacy trial and randomized to receive PfSPZ Vaccine at a dose determined during Part 1 of the trial (dose escalation), but likely to be 4.5x10^5, 9.0 x10^5and 1.8 x 10^6 administered x 3 doses ; and NS placebo administered x 3 doses, all by DVI administered at 8 week intervals.

Participants (N = 416, with 104 in each study arm) will be randomly assigned in a double blinded fashion to receive one of the following PfSPZ Vaccine regimes:

Group 1 (N=104): The highest dose that is determined to be safe and well tolerated in the Part 1 trial, administered in 3 doses by DVI at 0, 8 and 16 weeks. Likely dosage will be 1.8 x 10^6 PfSPZ per dose.

Group 2 (N=104): The second highest dose, which is half of the highest dose, administered in 3 doses by DVI at 0, 8 and 16 weeks. Likely dosage will be 9.0 x 10^5 PfSPZ per dose.

Group 3 (N=104): A lower dose (half of the second highest dose) administered in 3 doses by DVI at 0, 8, 16 weeks. Likely dosage will be 4.5x 10^5 PfSPZ per dose.

Group 4 (N=104): A placebo arm, will receive NS by DVI, 3 times at 8 week intervals.

  Eligibility

Ages Eligible for Study:   5 Months to 9 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy children 5 months - 9 years inclusive (Part 1) and healthy infants 5-12 months inclusive (Part 2)
  • HIV negative
  • Able to participate for the duration of the study.
  • Parents/guardians over the age of 18 years able and willing to provide informed consent/permission. The consent/permission will be in writing. For adult parents or guardians who are illiterate, an impartial witness can sign the consent/permission form on behalf of the parent and the parent/guardian will provide a thumb print.

Exclusion Criteria:

  • Positive HIV test or breastfeeding infants or children of a known HIV positive mother (per Kenyan guidelines, these HIV exposed breastfeeding children should be on cotrimoxazole)
  • Refusal of HIV testing
  • Elevated ALT (liver function test) ≥2x ULN ( ALT >84 U/L)
  • Abnormal hematological parameters defined as: hemoglobin < 8 g/dl, WBC <1500 / mm3, neutrophils <750/ mm3, platelet count <75.000/ mm3
  • Abnormal renal function test with creatinine >0.9 mg/dL
  • Known sickle cell disease
  • Current use of systemic immunosuppressant pharmacotherapy
  • Current significant medical condition (cardiac, hepatic, renal, or hematological) or evidence of any other serious underlying medical condition identified by medical history, physical examination, or laboratory examination
  • History of a splenectomy
  • History of neurologic disorder (including seizures, other than uncomplicated febrile seizures)
  • Known allergy to any component of the vaccine formulation, history of anaphylactic response to mosquito-bites, or known allergy to first or second line anti-malarials used to treat malaria
  • Plan to participate in another investigational vaccine/drug research during or within 1 month of this study end
  • Prior participation in a malaria vaccine trial
  • Participation in the PfSPZ Vaccine Trial Part 1 (for Part 2 only)
  • History of any other illness or condition which, in the investigator's judgment, may substantially increase the risk associated with the subject's participation in the protocol or compromise the scientific objectives
  • Child/orphan in institutional care
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02687373

Contacts
Contact: Martina Oneko, MD +254 717 747279 moneko@kemricdc.org
Contact: Aaron M. Samuels, MD, MHS +254 724 255633 iyp2@cdc.gov

Locations
Kenya
Center for Global Health Research, KEMRI Recruiting
Kisian, Siaya County, Kenya
Contact: Martina Oneka, MD    +254 717 747279    moneko@kemricdc.org   
Principal Investigator: Martina Oneko, MD         
Sponsors and Collaborators
Sanaria Inc.
Kenya Medical Research Institute
Centers for Disease Control and Prevention
National Institutes of Health (NIH)
University of Maryland
Investigators
Principal Investigator: Martina Oneko, MD Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya
  More Information

Responsible Party: Sanaria Inc.
ClinicalTrials.gov Identifier: NCT02687373     History of Changes
Other Study ID Numbers: KEMRI/SERU/CGHR/017/3129
CDC IRB Protocol #6787 ( Other Identifier: CDC, USA )
Study First Received: February 9, 2016
Last Updated: July 20, 2016

Keywords provided by Sanaria Inc.:
Plasmodium falciparum
PfSPZ Vaccine

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 25, 2017