MalariaPhase 1/2NCT02687373
Safety, Tolerability and Efficacy of PfSPZ Vaccine in Healthy Children and Infants 5 Months - 9 Years Living in Kenya
A Phase 1/2 study testing PfSPZ Vaccine and Normal Saline in people with Malaria, run by Sanaria Inc. at 1 site in Kenya.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 5 months to 9 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- PfSPZ Vaccine and Normal Saline
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 337 participants
- Where
- 1 siteKenya
- Study dates
- 21 Jul 2016to 14 Aug 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 months to 9 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
Who cannot join
- 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 and other inherited blood cell disorders like thalassemia and G6PD deficiency
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Malaria
- Being tested
- PfSPZ Vaccine, Normal Saline
- Keywords
- Plasmodium falciparum, PfSPZ Vaccine
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PfSPZ VaccineBiological
Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites
Normal SalineOther
0.9% Sodium chloride
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Grp 1A - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 1: Grp 1A - Normal Saline | Placebo comparator | Children aged 5-9 years (inclusive) of age will be enrolled in this group.
N=4; Normal saline administered DVI, as a single vaccination. Receives: Other: Normal Saline |
| Part 1: Grp 1B - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 1: Grp 1B - Normal Saline | Placebo comparator | 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. Receives: Other: Normal Saline |
| Part 1: Grp 1C - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 1: Grp 1C - Normal Saline | Placebo comparator | 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. Receives: Other: Normal Saline |
| Part 1: Grp 2A - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 1: Grp 2A - Normal Saline | Placebo comparator | 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. Receives: Other: Normal Saline |
| Part 1: Grp 2B - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 1: Grp 2B - Normal Saline | Placebo comparator | 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. Receives: Other: Normal Saline |
| Part 1: Grp 2C - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 1: Grp 2C - Normal Saline | Placebo comparator | 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. Receives: Other: Normal Saline |
| Part 1: Grp 2D - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 1: Grp 2D - Normal Saline | Placebo comparator | 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. Receives: Other: Normal Saline |
| Part 1: Grp 2E - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 1: Grp 2E - Normal Saline | Placebo comparator | 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. Receives: Other: Normal Saline |
| Part 1: Grp 3A - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 1: Grp 3A - Normal Saline | Placebo comparator | 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. Receives: Other: Normal Saline |
| Part 1: Grp 3B - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 1: Grp 3B - Normal Saline | Placebo comparator | 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. Receives: Other: Normal Saline |
| Part 1: Grp 3C - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 1: Grp 3C - Normal Saline | Placebo comparator | 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. Receives: Other: Normal Saline |
| Part 1: Grp 3D - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 1: Grp 3D - Normal Saline | Placebo comparator | 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. Receives: Other: Normal Saline |
| Part 1: Grp 3E - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 1: Grp 3E - Normal Saline | Placebo comparator | 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. Receives: Other: Normal Saline |
| Part 2: Group 1 - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 2: Group 2 - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 2: Group 3 - PfSPZ Vaccine | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Part 2: Group 4 - Normal Saline | Placebo comparator | 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. Receives: Other: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1 - Incidence and type of adverse events (AE)
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.
Measured: Collected from day of each vaccination until day 28 post vaccination
Part 1 - Incidence and type of possibly/probably or definitely related serious adverse events (SAEs)
Incidence of all hospitalizations, deaths, disabilities caused by at least possibly related SAEs during study participation
Measured: Collected from day of first vaccination until close out visit (28 days for 3 lower doses, 84 days for 2 higher doses)
Part 1 - Assessment of Pf-specific antibodies in the different age categories and to the different vaccine doses
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.
Measured: Collected 1 week after each vaccination
Part 2 - Incidence and type of adverse events in infants 5-12 months of age following administration of PfSPZ Vaccine
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.
Measured: Collected from day of each vaccination until day 28 post vaccination
Part 2 - Incidence and type of possibly/probably or definitely related serious adverse events (SAEs) following administration of PfSPZ Vaccine
Incidence of all hospitalizations, deaths, disabilities caused by at least possibly related to the study product during the 12-month follow-up period.
Measured: Collected from day of first vaccination through 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
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.
Measured: Collected 1 week after the first and second vaccination and 2 weeks after the third vaccination.
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
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.
Measured: 2 weeks to 6 months after the last vaccine dose
Secondary outcomes (4)
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
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.
Measured: 2 weeks to 12 months after the last vaccine dose
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
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.
Measured: 2 weeks to 6 and 12 months after the last vaccine dose
Part 2 - Assessment of Pf-specific antibodies, parasite-specific T cell responses and RNA sequencing.
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.
Measured: 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
Part 2 - Assessment of Pf-specific antibodies, parasite-specific T cell responses and RNA sequencing to determine correlation of immune response with efficacy
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.
Measured: Entire study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2016 (estimated)
- Study start21 Jul 2016
- Primary completionAug 2018
- Study completion14 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 337 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanaria Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Kenya Medical Research Institute, Centers for Disease Control and Prevention, National Institutes of Health (NIH), University of Maryland
- Responsible party
- Sponsor
- Investigators
- Martina Oneko, MD, Principal investigator, Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02687373
- Sponsor's protocol ID
- KEMRI/SERU/CGHR/017/3129
- Other IDs
- CDC IRB Protocol #6787
- Status last verified
- Apr 2019
- First submitted
- 9 Feb 2016
- Last updated
- 19 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Oneko M, Steinhardt LC, Yego R, Wiegand RE, Swanson PA, Kc N, Akach D, Sang T, Gutman JR, Nzuu EL, Dungani A, Kim Lee Sim B, Oloo PN, Otieno K, Bii DK, Billingsley PF, James ER, Kariuki S, Samuels AM, Jongo S, Chebore W, Abdulla S, Daubenberger C, Mpina M, Styers D, Potter GE, Abarbanell G, Richie TL, Hoffman SL, Seder RA. Safety, immunogenicity and efficacy of PfSPZ Vaccine against malaria in infants in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trial. Nat Med. 2021 Sep;27(9):1636-1645. doi: 10.1038/s41591-021-01470-y. Epub 2021 Sep 13.
PubMed 34518679Oneko M, Cherop YR, Sang T, Gutman JR, Wiegand R, Nyang'au EM, Odila AD, Akach D, Hamel MJ, Samuels AM, Kariuki S, Abebe Y, Nzuu EL, Wijayalath W, James ER, Sim BKL, Billingsley PF, Richie TL, Hoffman SL, Seder RA, Steinhardt LC. Feasibility of direct venous inoculation of the radiation-attenuated Plasmodium falciparum whole sporozoite vaccine in children and infants in Siaya, western Kenya. Vaccine. 2020 Jun 15;38(29):4592-4600. doi: 10.1016/j.vaccine.2020.05.008. Epub 2020 May 19.
PubMed 32444192Steinhardt LC, Richie TL, Yego R, Akach D, Hamel MJ, Gutman JR, Wiegand RE, Nzuu EL, Dungani A, Kc N, Murshedkar T, Church LWP, Sim BKL, Billingsley PF, James ER, Abebe Y, Kariuki S, Samuels AM, Otieno K, Sang T, Kachur SP, Styers D, Schlessman K, Abarbanell G, Hoffman SL, Seder RA, Oneko M. Safety, Tolerability, and Immunogenicity of Plasmodium falciparum Sporozoite Vaccine Administered by Direct Venous Inoculation to Infants and Young Children: Findings From an Age De-escalation, Dose-Escalation, Double-blind, Randomized Controlled Study in Western Kenya. Clin Infect Dis. 2020 Aug 14;71(4):1063-1071. doi: 10.1093/cid/ciz925.
PubMed 31555824
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02687373
- Acronym / sponsor ID
- KEMRI/SERU/CGHR/017/3129
- Conditions
- Malaria
- Keywords
- Plasmodium falciparum, PfSPZ Vaccine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 337 participants (actual)
- Lead sponsor
- Sanaria Inc.Industry (pharma, biotech, devices)
- Collaborators
- Kenya Medical Research Institute, Centers for Disease Control and Prevention, National Institutes of Health (NIH), University of Maryland
- Study start
- 21 Jul 2016 (actual)
- Primary completion
- Aug 2018 (actual)
- Study completion
- 14 Aug 2018 (actual)
- First posted
- 22 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 30
| Arm | Type | Receives |
|---|---|---|
| Part 1: Grp 1A - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineChildren 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. |
| Part 1: Grp 1A - Normal Saline | Placebo comparator | Other: Normal SalineChildren aged 5-9 years (inclusive) of age will be enrolled in this group. N=4; Normal saline administered DVI, as a single vaccination. |
| Part 1: Grp 1B - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineChildren 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. |
| Part 1: Grp 1B - Normal Saline | Placebo comparator | Other: Normal SalineChildren 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. |
| Part 1: Grp 1C - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineChildren 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. |
| Part 1: Grp 1C - Normal Saline | Placebo comparator | Other: Normal SalineChildren 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. |
| Part 1: Grp 2A - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineChildren 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. |
| Part 1: Grp 2A - Normal Saline | Placebo comparator | Other: Normal SalineChildren 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. |
| Part 1: Grp 2B - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineChildren 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. |
| Part 1: Grp 2B - Normal Saline | Placebo comparator | Other: Normal SalineChildren 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. |
| Part 1: Grp 2C - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineChildren 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. |
| Part 1: Grp 2C - Normal Saline | Placebo comparator | Other: Normal SalineChildren 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. |
| Part 1: Grp 2D - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineChildren 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. |
| Part 1: Grp 2D - Normal Saline | Placebo comparator | Other: Normal SalineChildren 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. |
| Part 1: Grp 2E - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineChildren 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. |
| Part 1: Grp 2E - Normal Saline | Placebo comparator | Other: Normal SalineChildren 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. |
| Part 1: Grp 3A - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineChildren 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. |
| Part 1: Grp 3A - Normal Saline | Placebo comparator | Other: Normal SalineChildren 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. |
| Part 1: Grp 3B - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineChildren 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. |
| Part 1: Grp 3B - Normal Saline | Placebo comparator | Other: Normal SalineChildren 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. |
| Part 1: Grp 3C - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineChildren 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. |
| Part 1: Grp 3C - Normal Saline | Placebo comparator | Other: Normal SalineChildren 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. |
| Part 1: Grp 3D - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineChildren 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. |
| Part 1: Grp 3D - Normal Saline | Placebo comparator | Other: Normal SalineChildren 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. |
| Part 1: Grp 3E - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineChildren 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. |
| Part 1: Grp 3E - Normal Saline | Placebo comparator | Other: Normal SalineChildren 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. |
| Part 2: Group 1 - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineInfants 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. |
| Part 2: Group 2 - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineInfants 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. |
| Part 2: Group 3 - PfSPZ Vaccine | Experimental | Biological: PfSPZ VaccineInfants 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. |
| Part 2: Group 4 - Normal Saline | Placebo comparator | Other: Normal SalineInfants 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. |
Who may qualify
- Ages
- 5 months to 9 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PfSPZ VaccineAseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites | Biological | Part 1: Grp 1A - PfSPZ Vaccine, Part 1: Grp 1B - PfSPZ Vaccine, Part 1: Grp 1C - PfSPZ Vaccine, Part 1: Grp 2A - PfSPZ Vaccine, Part 1: Grp 2B - PfSPZ Vaccine, Part 1: Grp 2C - PfSPZ Vaccine, Part 1: Grp 2D - PfSPZ Vaccine, Part 1: Grp 2E - PfSPZ Vaccine, Part 1: Grp 3A - PfSPZ Vaccine, Part 1: Grp 3B - PfSPZ Vaccine, Part 1: Grp 3C - PfSPZ Vaccine, Part 1: Grp 3D - PfSPZ Vaccine, Part 1: Grp 3E - PfSPZ Vaccine, Part 2: Group 1 - PfSPZ Vaccine, Part 2: Group 2 - PfSPZ Vaccine, Part 2: Group 3 - PfSPZ Vaccine |
| Normal Saline0.9% Sodium chloride | Other | Part 1: Grp 1A - Normal Saline, Part 1: Grp 1B - Normal Saline, Part 1: Grp 1C - Normal Saline, Part 1: Grp 2A - Normal Saline, Part 1: Grp 2B - Normal Saline, Part 1: Grp 2C - Normal Saline, Part 1: Grp 2D - Normal Saline, Part 1: Grp 2E - Normal Saline, Part 1: Grp 3A - Normal Saline, Part 1: Grp 3B - Normal Saline, Part 1: Grp 3C - Normal Saline, Part 1: Grp 3D - Normal Saline, Part 1: Grp 3E - Normal Saline, Part 2: Group 4 - Normal Saline |
Primary outcome
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.
4 secondary outcomes
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2019.
- Derived from this study: PubMed 34518679Oneko M, Steinhardt LC, Yego R, Wiegand RE, Swanson PA, Kc N, Akach D, Sang T, Gutman JR, Nzuu EL, Dungani A, Kim Lee Sim B, Oloo PN, Otieno K, Bii DK, Billingsley PF, James ER, Kariuki S, Samuels AM, Jongo S, Chebore W, Abdulla S, Daubenberger C, Mpina M, Styers D, Potter GE, Abarbanell G, Richie TL, Hoffman SL, Seder RA. Safety, immunogenicity and efficacy of PfSPZ Vaccine against malaria in infants in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trial. Nat Med. 2021 Sep;27(9):1636-1645. doi: 10.1038/s41591-021-01470-y. Epub 2021 Sep 13.
- Derived from this study: PubMed 32444192Oneko M, Cherop YR, Sang T, Gutman JR, Wiegand R, Nyang'au EM, Odila AD, Akach D, Hamel MJ, Samuels AM, Kariuki S, Abebe Y, Nzuu EL, Wijayalath W, James ER, Sim BKL, Billingsley PF, Richie TL, Hoffman SL, Seder RA, Steinhardt LC. Feasibility of direct venous inoculation of the radiation-attenuated Plasmodium falciparum whole sporozoite vaccine in children and infants in Siaya, western Kenya. Vaccine. 2020 Jun 15;38(29):4592-4600. doi: 10.1016/j.vaccine.2020.05.008. Epub 2020 May 19.
- Derived from this study: PubMed 31555824Steinhardt LC, Richie TL, Yego R, Akach D, Hamel MJ, Gutman JR, Wiegand RE, Nzuu EL, Dungani A, Kc N, Murshedkar T, Church LWP, Sim BKL, Billingsley PF, James ER, Abebe Y, Kariuki S, Samuels AM, Otieno K, Sang T, Kachur SP, Styers D, Schlessman K, Abarbanell G, Hoffman SL, Seder RA, Oneko M. Safety, Tolerability, and Immunogenicity of Plasmodium falciparum Sporozoite Vaccine Administered by Direct Venous Inoculation to Infants and Young Children: Findings From an Age De-escalation, Dose-Escalation, Double-blind, Randomized Controlled Study in Western Kenya. Clin Infect Dis. 2020 Aug 14;71(4):1063-1071. doi: 10.1093/cid/ciz925.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martina Oneko, MD principal investigator
Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PfSPZ Vaccine and Normal Saline in people with Malaria, run by Sanaria Inc. at 1 site in Kenya.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1 - Incidence and type of adverse events (AE) (time frame: Collected from day of each vaccination until day 28 post vaccination). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02687373, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2019.