MalariaPhase 1NCT02613520
Safety and Immunogenicity in Age De-Escalation of PfSPZ Vaccine in Tanzanian Adults, Children, and Infants
A Phase 1 study testing PfSPZ Vaccine, Normal Saline and PfSPZ Challenge (for CHMI) in people with Malaria, run by Sanaria Inc. at 1 site in Tanzania.
Trial summary
The present trial will evaluate safety and tolerability as well as the vaccine-induced humoral and cellular immune responses in healthy Tanzanian adults, adolescents, children, and infants who receive doses of 1.8x10^6, 9.0x10^5, 4.5x10^5 or 2.7x10^5 PfSPZ of PfSPZ Vaccine by direct venous inoculation (DVI),compared… Read more about this study
- Who is it for?
- Ages 6 months to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- PfSPZ Vaccine, Normal Saline and PfSPZ Challenge (for CHMI)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 105 participants
- Where
- 1 siteTanzania
- Study dates
- Dec 2015to Mar 2017
- Phase
- Phase 1
- 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 6 months to 45 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Healthy males and females, based on clinical and laboratory findings
- From the age 6 months to 45 years
- Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or adolescents, children and infants with Z-score of the selected indicator ([weight-for-height], [(height and BMI) for age]) category within ±2SD as detailed in protocol
- Long term (at least one year) or permanent residence in the Bagamoyo town or nearby villages
- Agreement to release medical information and to inform the study doctor concerning contraindications for participation in the study
- Willingness to be attended to by a study clinician and take all necessary medications prescribed during study period
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- Agreement to provide contact information of a third party household member or close friend to study team
- Availability through mobile phone 24 hours during the entire study period
- Agreement not to participate in another clinical trial during the study period
- Agreement not to donate blood during the study period
- Able and willing to complete the study visit schedule over the study follow up period, including the hospitalizations required for protocol compliance
- Willingness to undergo HIV, hepatitis B (HBV) and hepatitis C (HCV) tests
- Volunteer (subjects 18 years of age and older) and parent or guardian signing informed consent (for subjects <18 years of age) is able to demonstrate their understanding of the study by responding correctly to 10 out of 10 true/false statements (in a maximum of two attempts for those who failed to respond correctly to all true/false statements in the first attempt)
- Signed written informed consent, in accordance with local practice, provided by adult volunteers, parents or legal representatives and relevant assent for children participants as applicable
- Free from malaria parasitaemia by blood smear at enrolment
- Free from helminth infections at enrolment, or diagnosed with helminthes and treated appropriately to eliminate infestation
- Female volunteers aged 9 years and above must be non-pregnant (as demonstrated by a negative serum pregnancy test), and provide consent / assent of their willingness to take protocol-defined measures not to become pregnant during the study and safety follow-up period
Who cannot join
- Previous receipt of an investigational malaria vaccine or drug in the last 5 years
- Participation in any other clinical study involving investigational medicinal products within 30 days prior to the onset of the study or during the study period
- History of arrhythmias or prolonged QT-interval or other cardiac disease, or Clinically significant abnormalities in electrocardiogram (ECG) at screening
- Positive family history in a 1st or 2nd degree relative for cardiac disease at age <50 years old
- A history of psychiatric disease
- Suffering from any chronic illness including; diabetes mellitus, cancer or HIV/AIDS
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- Any confirmed or suspected immunosuppressive or immune-deficient condition, including asplenia
- History of drug or alcohol abuse interfering with normal social function
- The use of chronic immunosuppressive drugs or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids are allowed) and during the study period
- Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis
- Positive HIV, hepatitis B virus or hepatitis C virus tests
- Volunteers who are suspected as having clinically active TB by history or physical examination with positive QuantiFERON-TB Gold Test In-Tube assay
- Symptoms, physical signs and laboratory values suggestive of systemic disorders including renal, hepatic, blood, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, and other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers
- Any medical, social condition, or occupational reason that, in the judgment of the investigator, is a contraindication to protocol participation or impairs the volunteer's ability to give informed consent, increases the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
Trial locations and contacts
1 site in 1 country.
Tanzania1 site
Bagamoyo Research and Training center of the Ifakara Health Institute
Bagamoyo
About this study
Official title: Clinical Trial to Evaluate the Safety and Immunogenicity in Age De-Escalation of Direct Venous Inoculation of a Plasmodium Falciparum Sporozoite Vaccine in Tanzanian Adults, Children, and Infants
The present trial will evaluate safety and tolerability as well as the vaccine-induced humoral and cellular immune responses in healthy Tanzanian adults, adolescents, children, and infants who receive doses of 1.8x10^6, 9.0x10^5, 4.5x10^5 or 2.7x10^5 PfSPZ of PfSPZ Vaccine by direct venous inoculation (DVI),compared with control groups receiving normal saline (NS) placebo by DVI. In addition, as an exploratory objective, controlled human malaria infection (CHMI) will be used to assess efficacy in adults three weeks following immunization.
Read the detailed description
This is a single center trial to assess the safety, tolerability and immunogenicity of PfSPZ Vaccine administered by direct venous inoculation (DVI) to healthy Tanzanian adults, adolescents, and children and infants. 105 healthy male and female; adults, adolescents, children and infant volunteers, aged from 6 months to 45 years, who live in the Bagamoyo Township will be enrolled based on pre-defined inclusion and exclusion criteria implemented according to international ethical standards.
The safety and tolerability of PfSPZ Vaccine administered as three doses of either 9.0x10^5 PfSPZ or 1.8x10^6 PfSPZ to healthy Tanzanian adults, adolescents, and children 6 years of age or older; and three doses of 4.5x10^5 PfSPZ or 9.0x10^5 PfSPZ to healthy Tanzanian children 1 to 5 years of age and infants 6 to 11 months of age, in each case compared to NS controls, will be evaluated. In addition, as an exploratory objective, controlled human malaria infection (CHMI) will be used to assess efficacy in adults three weeks following immunization.
Study Design: This is a single center trial with ten groups (Groups 1a/b: ages 18-45; Group 2a/b: ages 11-17; Group 3a/b: ages 6-10; Group 4a/b: ages 1-5; and Group 5b/c: ages 6months-11 months) each with 6 subjects receiving PfSPZ Vaccine and 3 subjects receiving NS and an eleventh smaller group (Group 5a: ages 6months-11months) with 3 subjects receiving PfSPZ Vaccine; two of these groups (Group 1a/b) contain adult volunteers and will have infectivity controls (CHMI 1 and 2) each having 3 subjects, after the vaccination phase of the study. The adult volunteers will undergo CHMI 3 weeks after the last immunization.
For the first immunization, two volunteers (out of six) in Group 1a will receive 9x10^5 of PfSPZ Vaccine by DVI as sentinels, to demonstrate safety and tolerability. At the same time, one (out of three) corresponding control volunteers will receive NS, in order to maintain blinding. Approximately 24 hours later, provided criteria for calling an ad hoc SMC meeting are not met, the remaining four volunteers in Group 1a will also receive a 9x10^5 PfSPZ dose of the vaccine and the remaining two placebo recipients will receive NS.
After review of at least +14 days post vaccination safety data for Group 1a by the SMC, if there are no significant safety concerns, two volunteers (out of six) in Group 1b will receive 1.8x10^6 PfSPZ, and two volunteers (out of six) in each of the Groups 2a and 3a will receive 9x10^5 PfSPZ, of the PfSPZ Vaccine, to demonstrate safety and tolerability, and each of these sentinel groups will be joined by one corresponding NS control in order to maintain blinding. Approximately 24 hours later, provided criteria for calling an ad hoc SMC meeting are not met, the remaining four volunteers in Group 1b will receive 1.8x10^6 PfSPZ and the remaining four volunteers in each of Groups 2a and 3a will receive 9x10^5 PfSPZ of the PfSPZ Vaccine, and the remaining placebo recipients will receive NS.
After review of at least +14 days post vaccination safety data for Groups 1b, 2a and 3a by the SMC, if there are no significant safety concerns, two volunteers (out of six) in each of the Groups 2b and 3b will receive 1.8x10^6 PfSPZ, those in Group 4a will receive 4.5x10^5 PfSPZ and all 3 volunteers in Group 5a will receive 2.7x10^5 PfSPZ of PfSPZ Vaccine, to demonstrate safety and tolerability, and each of the sentinel groups (two volunteers from Groups 2b, 3b and 4a) will be joined by one NS control in order to maintain blinding. Approximately 24 hours later, provided criteria for calling an ad hoc SMC meeting are not met, the remaining four volunteers in Groups 2b, 3b and 4a will receive their appropriate dose of PfSPZ Vaccine (1.8x10^6 PfSPZ, 1.8x10^6 PfSPZ, and 4.5x10^5 PfSPZ, respectively), and the placebo recipients will receive NS.
Escalation from the small group of infants, (Group 5a, n=3) receiving a single dose of 2.7x10^5 PfSPZ, to the full group (Group 5b, n=6) receiving three doses of 4.5x10^5 PfSPZ, will proceed without SMC review if criteria for calling an ad hoc SMC meeting are not met. However, if the criteria are met, an ad hoc SMC meeting will be called to review the data, and dose escalation to 4.5x10^5 PfSPZ will be postponed until the recommendations of the SMC are available. The interval between the 2.7x10^5 PfSPZ small group and the 4.5x10^5 PfSPZ larger group will be a minimum of three days.
After review of at least +14 days post vaccination, safety data for Groups 2b, 3b, 4a, 5a and 5b by the SMC, if there are no significant safety concerns, two volunteers (out of six) in each of the Groups 4b and 5c will receive 9x10^5 PfSPZ, to demonstrate safety and tolerability. At the same time, one (out of three) corresponding control volunteers will receive NS, in order to maintain blinding. Approximately 24 hours later, provided criteria for calling an ad hoc SMC meeting are not met, the remaining four volunteers in Group 4b and 5c will receive 9x10^5 PfSPZ dose of the vaccine, and the placebo recipients will receive NS.
- Conditions
- Malaria
- Being tested
- PfSPZ Vaccine, Normal Saline, PfSPZ Challenge (for CHMI)
- Keywords
- PfSPZ Vaccine, Plasmodium falciparum
- 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
Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)
Normal SalineOther
0.9% Sodium chloride
PfSPZ Challenge (for CHMI)Biological
live, infectious, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Challenge) Controlled human malaria infection (CHMI) by direct venous inoculation of 3,200 PfSPZ Challenge
| Study group | Role | What they receive |
|---|---|---|
| Group 1a (PfSPZ Vaccine) | Experimental | 18- 45 years; n=6; 3 doses of 9 x 10^5 PfSPZ Vaccine given 8 weeks apart. Volunteers will undergo CHMI with PfSPZ Challenge 3 weeks after the last immunization. Receives: Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (for CHMI) |
| Group 1a (normal saline) | Placebo comparator | 18- 45 years; n=3; 3 doses of normal saline given 8 weeks apart. Volunteers will undergo CHMI with PfSPZ Challenge 3 weeks after the last immunization. Receives: Other: Normal Saline; Biological: PfSPZ Challenge (for CHMI) |
| Group 1a (CHMI controls) | Other | 18- 45 years; n=6; volunteers will not receive any intervention, but will serve only as infectivity controls; 3 volunteers each, for CHMI 1 and for CHMI 2 in Group 1a. Volunteers will be injected with PfSPZ Challenge (for CHMI). Receives: Biological: PfSPZ Challenge (for CHMI) |
| Group 1b (PfSPZ Vaccine) | Experimental | 18- 45 years; n=6; 3 doses of 1.8 x 10^6 PfSPZ Vaccine given 8 weeks apart. Volunteers will undergo CHMI with PfSPZ Challenge 3 weeks after the last immunization. Receives: Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (for CHMI) |
| Group 1b (normal saline) | Placebo comparator | 18- 45 years; n=3; 3 doses of normal saline given 8 weeks apart. Volunteers will undergo CHMI with PfSPZ Challenge 3 weeks after the last immunization. Receives: Other: Normal Saline; Biological: PfSPZ Challenge (for CHMI) |
| Group 1b (CHMI controls) | Other | 18- 45 years; n=6; volunteers will not receive any intervention, but will serve only as infectivity controls; 3 volunteers each, for CHMI 1 and for CHMI 2 in Group 1b. Volunteers will be injected with PfSPZ Challenge (for CHMI). Receives: Biological: PfSPZ Challenge (for CHMI) |
| Group 2a (PfSPZ Vaccine) | Experimental | 11-17 years; n=6; 3 doses of 9.0 x 10^5 PfSPZ Vaccine given 8 weeks apart. Receives: Biological: PfSPZ Vaccine |
| Group 2a (normal saline) | Placebo comparator | 11-17 years; n=3; 3 doses of normal saline given 8 weeks apart. Receives: Other: Normal Saline |
| Group 2b (PfSPZ Vaccine) | Experimental | 11-17 years; n=6; 3 doses of 1.8 x 10^6 PfSPZ Vaccine given 8 weeks apart. Receives: Biological: PfSPZ Vaccine |
| Group 2b (normal saline) | Placebo comparator | 11-17 years; n=3; 3 doses of normal saline given 8 weeks apart. Receives: Other: Normal Saline |
| Group 3a (PfSPZ Vaccine) | Experimental | 6-10 years; n=6; 3 doses of 9.0 x 10^5 PfSPZ Vaccine given 8 weeks apart. Receives: Biological: PfSPZ Vaccine |
| Group 3a (normal saline) | Placebo comparator | 6-10 years; n=3; 3 doses of normal saline given 8 weeks apart. Receives: Other: Normal Saline |
| Group 3b (PfSPZ Vaccine) | Experimental | 6-10 years; n=6; 3 doses of 1.8 x 10^6 PfSPZ Vaccine given 8 weeks apart. Receives: Biological: PfSPZ Vaccine |
| Group 3b (normal saline) | Placebo comparator | 6-10 years; n=3; 3 doses of normal saline given 8 weeks apart. Receives: Other: Normal Saline |
| Group 4a (PfSPZ Vaccine) | Experimental | 1-5 years; n=6; 3 doses of 4.5 x 10^5 PfSPZ Vaccine given 8 weeks apart. Receives: Biological: PfSPZ Vaccine |
| Group 4a (normal saline) | Placebo comparator | 1-5 years; n=3; 3 doses of normal saline given 8 weeks apart. Receives: Other: Normal Saline |
| Group 4b (PfSPZ Vaccine) | Experimental | 1-5 years; n=6; 3 doses of 9.0 x 10^5 PfSPZ Vaccine given 8 weeks apart. Receives: Biological: PfSPZ Vaccine |
| Group 4b (normal saline) | Placebo comparator | 1-5 years; n=3; 3 doses of normal saline given 8 weeks apart. Receives: Other: Normal Saline |
| Group 5a (PfSPZ Vaccine) | Experimental | 6-11 months; n=3; 1 dose of 2.7 x 10^5 PfSPZ Vaccine. Receives: Biological: PfSPZ Vaccine |
| Group 5b (PfSPZ Vaccine) | Experimental | 6-11 months; n=6; 3 doses of 4.5 x 10^5 PfSPZ Vaccine given 8 weeks apart. Receives: Biological: PfSPZ Vaccine |
| Group 5b (normal saline) | Placebo comparator | 6-11 months; n=3; 3 doses of normal saline given 8 weeks apart. Receives: Other: Normal Saline |
| Group 5c (PfSPZ Vaccine) | Experimental | 6-11 months; n=6; 3 doses of 9.0 x 10^5 PfSPZ Vaccine given 8 weeks apart. Receives: Biological: PfSPZ Vaccine |
| Group 5c (normal saline) | Placebo comparator | 6-11 months; n=3; 3 doses of normal saline given 8 weeks apart. Receives: Other: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and type of Adverse Events
Incidence and type of adverse events (including breakthrough infections), vital signs, clinical laboratory assessments, physical examination findings post first immunization onwards.
- Occurrence of solicited symptoms during a 7-day surveillance period after vaccination (day of vaccination (Vx) and +7 days post vaccination)
- Occurrence of unsolicited symptoms during a 28-day surveillance period after each vaccination.
- Occurrence of serious adverse events during the study period.
- Occurrence of Pf infection of vaccine type detected at any point after the first vaccination (retrospectively determined).
Measured: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Secondary outcomes (4)
Level of Antibodies against Pf proteins in volunteer sera
- Antibody titres to pre-erythrocytic stage and erythrocytic stage antigens[PfCSP, PfLSA-1, PfEBA-175 , PfMSP-1, PfMSP-5, EXP-1] by ELISA
- Antibody titres to Pf sporozoites, asexual and sexual erythrocytic stage parasites by IFA.
- Analysis of antibodies to proteins in the Pf proteome array chip.
Measured: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Inhibitory Capacity of Volunteer Sera against in vitro Sporozoite Invasion of Hepatocytes
Capacity of sera from immunized volunteers to inhibit sporozoite invasion (ISI) of hepatocytes in vitro by ISI assay
Measured: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Quantitation of cellular immune responses against Pf proteins in volunteers
- Identification of number of vaccine induced PBMCs following Intracellular cytokine staining by flow cytometry after stimulation with PfSPZ or Pf-infected erythrocytes, peptide pools and P. falciparum infected primary human hepatocyte cell lines.
- Identification of numbers of vaccine induced CD4 and CD8 T cells following FluoroSpot assay after stimulation with PfSPZ or Pf-infected erythrocytes.
Measured: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Whole genome expression profiles of volunteer
Human gene expression profiling focusing on immune response genes in volunteers
Measured: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2015 (estimated)
- Study startDec 2015
- Primary completionFeb 2017
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanaria Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ifakara Health Institute, Swiss Tropical & Public Health Institute, Medical Care Development, Inc., Tanzania Commission for Science and Technology, Government of Equatorial Guinea, Marathon Oil Corporation, Noble Oil Services
- Responsible party
- Sponsor
- Investigators
- Said Jongo, MD, MMED, Principal investigator, Ifakara Health Institute (IHI), Bagamoyo, Tanzania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02613520
- Sponsor's protocol ID
- BSPZV2
- Status last verified
- Dec 2017
- First submitted
- 17 Nov 2015
- Last updated
- 15 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jongo SA, Church LWP, Mtoro AT, Schindler T, Chakravarty S, Ruben AJ, Swanson PA, Kassim KR, Mpina M, Tumbo AM, Milando FA, Qassim M, Juma OA, Bakari BM, Simon B, James ER, Abebe Y, Kc N, Saverino E, Fink M, Cosi G, Gondwe L, Studer F, Styers D, Seder RA, Schindler T, Billingsley PF, Daubenberger C, Sim BKL, Tanner M, Richie TL, Abdulla S, Hoffman SL. Increase of Dose Associated With Decrease in Protection Against Controlled Human Malaria Infection by PfSPZ Vaccine in Tanzanian Adults. Clin Infect Dis. 2020 Dec 31;71(11):2849-2857. doi: 10.1093/cid/ciz1152.
PubMed 31782768Schindler T, Jongo S, Studer F, Mpina M, Mwangoka G, Mswata S, Ramadhani K, Sax J, Church LWP, Richie TL, Tanner M, Hoffman SL, Abdulla S, Daubenberger C. Two cases of long-lasting, sub-microscopic Plasmodium malariae infections in adults from coastal Tanzania. Malar J. 2019 Apr 29;18(1):149. doi: 10.1186/s12936-019-2787-x.
PubMed 31036014
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial to Evaluate the Safety and Immunogenicity in Age De-Escalation of Direct Venous Inoculation of a Plasmodium Falciparum Sporozoite Vaccine in Tanzanian Adults, Children, and Infants
- ClinicalTrials.gov ID
- NCT02613520
- Acronym / sponsor ID
- BSPZV2
- Conditions
- Malaria
- Keywords
- PfSPZ Vaccine, Plasmodium falciparum
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Sanaria Inc.Industry (pharma, biotech, devices)
- Collaborators
- Ifakara Health Institute, Swiss Tropical & Public Health Institute, Medical Care Development, Inc., Tanzania Commission for Science and Technology, Government of Equatorial Guinea, Marathon Oil Corporation, Noble Oil Services
- Study start
- Dec 2015 (actual)
- Primary completion
- Feb 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 24 Nov 2015 (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.
The present trial will evaluate safety and tolerability as well as the vaccine-induced humoral and cellular immune responses in healthy Tanzanian adults, adolescents, children, and infants who receive doses of 1.8x10^6, 9.0x10^5, 4.5x10^5 or 2.7x10^5 PfSPZ of PfSPZ Vaccine by direct venous inoculation (DVI),compared with control groups receiving normal saline (NS) placebo by DVI. In addition, as an exploratory objective, controlled human malaria infection (CHMI) will be used to assess efficacy in adults three weeks following immunization.
Detailed description
This is a single center trial to assess the safety, tolerability and immunogenicity of PfSPZ Vaccine administered by direct venous inoculation (DVI) to healthy Tanzanian adults, adolescents, and children and infants. 105 healthy male and female; adults, adolescents, children and infant volunteers, aged from 6 months to 45 years, who live in the Bagamoyo Township will be enrolled based on pre-defined inclusion and exclusion criteria implemented according to international ethical standards.
The safety and tolerability of PfSPZ Vaccine administered as three doses of either 9.0x10^5 PfSPZ or 1.8x10^6 PfSPZ to healthy Tanzanian adults, adolescents, and children 6 years of age or older; and three doses of 4.5x10^5 PfSPZ or 9.0x10^5 PfSPZ to healthy Tanzanian children 1 to 5 years of age and infants 6 to 11 months of age, in each case compared to NS controls, will be evaluated. In addition, as an exploratory objective, controlled human malaria infection (CHMI) will be used to assess efficacy in adults three weeks following immunization.
Study Design: This is a single center trial with ten groups (Groups 1a/b: ages 18-45; Group 2a/b: ages 11-17; Group 3a/b: ages 6-10; Group 4a/b: ages 1-5; and Group 5b/c: ages 6months-11 months) each with 6 subjects receiving PfSPZ Vaccine and 3 subjects receiving NS and an eleventh smaller group (Group 5a: ages 6months-11months) with 3 subjects receiving PfSPZ Vaccine; two of these groups (Group 1a/b) contain adult volunteers and will have infectivity controls (CHMI 1 and 2) each having 3 subjects, after the vaccination phase of the study. The adult volunteers will undergo CHMI 3 weeks after the last immunization.
For the first immunization, two volunteers (out of six) in Group 1a will receive 9x10^5 of PfSPZ Vaccine by DVI as sentinels, to demonstrate safety and tolerability. At the same time, one (out of three) corresponding control volunteers will receive NS, in order to maintain blinding. Approximately 24 hours later, provided criteria for calling an ad hoc SMC meeting are not met, the remaining four volunteers in Group 1a will also receive a 9x10^5 PfSPZ dose of the vaccine and the remaining two placebo recipients will receive NS.
After review of at least +14 days post vaccination safety data for Group 1a by the SMC, if there are no significant safety concerns, two volunteers (out of six) in Group 1b will receive 1.8x10^6 PfSPZ, and two volunteers (out of six) in each of the Groups 2a and 3a will receive 9x10^5 PfSPZ, of the PfSPZ Vaccine, to demonstrate safety and tolerability, and each of these sentinel groups will be joined by one corresponding NS control in order to maintain blinding. Approximately 24 hours later, provided criteria for calling an ad hoc SMC meeting are not met, the remaining four volunteers in Group 1b will receive 1.8x10^6 PfSPZ and the remaining four volunteers in each of Groups 2a and 3a will receive 9x10^5 PfSPZ of the PfSPZ Vaccine, and the remaining placebo recipients will receive NS.
After review of at least +14 days post vaccination safety data for Groups 1b, 2a and 3a by the SMC, if there are no significant safety concerns, two volunteers (out of six) in each of the Groups 2b and 3b will receive 1.8x10^6 PfSPZ, those in Group 4a will receive 4.5x10^5 PfSPZ and all 3 volunteers in Group 5a will receive 2.7x10^5 PfSPZ of PfSPZ Vaccine, to demonstrate safety and tolerability, and each of the sentinel groups (two volunteers from Groups 2b, 3b and 4a) will be joined by one NS control in order to maintain blinding. Approximately 24 hours later, provided criteria for calling an ad hoc SMC meeting are not met, the remaining four volunteers in Groups 2b, 3b and 4a will receive their appropriate dose of PfSPZ Vaccine (1.8x10^6 PfSPZ, 1.8x10^6 PfSPZ, and 4.5x10^5 PfSPZ, respectively), and the placebo recipients will receive NS.
Escalation from the small group of infants, (Group 5a, n=3) receiving a single dose of 2.7x10^5 PfSPZ, to the full group (Group 5b, n=6) receiving three doses of 4.5x10^5 PfSPZ, will proceed without SMC review if criteria for calling an ad hoc SMC meeting are not met. However, if the criteria are met, an ad hoc SMC meeting will be called to review the data, and dose escalation to 4.5x10^5 PfSPZ will be postponed until the recommendations of the SMC are available. The interval between the 2.7x10^5 PfSPZ small group and the 4.5x10^5 PfSPZ larger group will be a minimum of three days.
After review of at least +14 days post vaccination, safety data for Groups 2b, 3b, 4a, 5a and 5b by the SMC, if there are no significant safety concerns, two volunteers (out of six) in each of the Groups 4b and 5c will receive 9x10^5 PfSPZ, to demonstrate safety and tolerability. At the same time, one (out of three) corresponding control volunteers will receive NS, in order to maintain blinding. Approximately 24 hours later, provided criteria for calling an ad hoc SMC meeting are not met, the remaining four volunteers in Group 4b and 5c will receive 9x10^5 PfSPZ dose of the vaccine, and the placebo recipients will receive NS.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 23
| Arm | Type | Receives |
|---|---|---|
| Group 1a (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine, Biological: PfSPZ Challenge (for CHMI)18- 45 years; n=6; 3 doses of 9 x 10^5 PfSPZ Vaccine given 8 weeks apart. Volunteers will undergo CHMI with PfSPZ Challenge 3 weeks after the last immunization. |
| Group 1a (normal saline) | Placebo comparator | Other: Normal Saline, Biological: PfSPZ Challenge (for CHMI)18- 45 years; n=3; 3 doses of normal saline given 8 weeks apart. Volunteers will undergo CHMI with PfSPZ Challenge 3 weeks after the last immunization. |
| Group 1a (CHMI controls) | Other | Biological: PfSPZ Challenge (for CHMI)18- 45 years; n=6; volunteers will not receive any intervention, but will serve only as infectivity controls; 3 volunteers each, for CHMI 1 and for CHMI 2 in Group 1a. Volunteers will be injected with PfSPZ Challenge (for CHMI). |
| Group 1b (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine, Biological: PfSPZ Challenge (for CHMI)18- 45 years; n=6; 3 doses of 1.8 x 10^6 PfSPZ Vaccine given 8 weeks apart. Volunteers will undergo CHMI with PfSPZ Challenge 3 weeks after the last immunization. |
| Group 1b (normal saline) | Placebo comparator | Other: Normal Saline, Biological: PfSPZ Challenge (for CHMI)18- 45 years; n=3; 3 doses of normal saline given 8 weeks apart. Volunteers will undergo CHMI with PfSPZ Challenge 3 weeks after the last immunization. |
| Group 1b (CHMI controls) | Other | Biological: PfSPZ Challenge (for CHMI)18- 45 years; n=6; volunteers will not receive any intervention, but will serve only as infectivity controls; 3 volunteers each, for CHMI 1 and for CHMI 2 in Group 1b. Volunteers will be injected with PfSPZ Challenge (for CHMI). |
| Group 2a (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine11-17 years; n=6; 3 doses of 9.0 x 10^5 PfSPZ Vaccine given 8 weeks apart. |
| Group 2a (normal saline) | Placebo comparator | Other: Normal Saline11-17 years; n=3; 3 doses of normal saline given 8 weeks apart. |
| Group 2b (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine11-17 years; n=6; 3 doses of 1.8 x 10^6 PfSPZ Vaccine given 8 weeks apart. |
| Group 2b (normal saline) | Placebo comparator | Other: Normal Saline11-17 years; n=3; 3 doses of normal saline given 8 weeks apart. |
| Group 3a (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine6-10 years; n=6; 3 doses of 9.0 x 10^5 PfSPZ Vaccine given 8 weeks apart. |
| Group 3a (normal saline) | Placebo comparator | Other: Normal Saline6-10 years; n=3; 3 doses of normal saline given 8 weeks apart. |
| Group 3b (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine6-10 years; n=6; 3 doses of 1.8 x 10^6 PfSPZ Vaccine given 8 weeks apart. |
| Group 3b (normal saline) | Placebo comparator | Other: Normal Saline6-10 years; n=3; 3 doses of normal saline given 8 weeks apart. |
| Group 4a (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine1-5 years; n=6; 3 doses of 4.5 x 10^5 PfSPZ Vaccine given 8 weeks apart. |
| Group 4a (normal saline) | Placebo comparator | Other: Normal Saline1-5 years; n=3; 3 doses of normal saline given 8 weeks apart. |
| Group 4b (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine1-5 years; n=6; 3 doses of 9.0 x 10^5 PfSPZ Vaccine given 8 weeks apart. |
| Group 4b (normal saline) | Placebo comparator | Other: Normal Saline1-5 years; n=3; 3 doses of normal saline given 8 weeks apart. |
| Group 5a (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine6-11 months; n=3; 1 dose of 2.7 x 10^5 PfSPZ Vaccine. |
| Group 5b (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine6-11 months; n=6; 3 doses of 4.5 x 10^5 PfSPZ Vaccine given 8 weeks apart. |
| Group 5b (normal saline) | Placebo comparator | Other: Normal Saline6-11 months; n=3; 3 doses of normal saline given 8 weeks apart. |
| Group 5c (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine6-11 months; n=6; 3 doses of 9.0 x 10^5 PfSPZ Vaccine given 8 weeks apart. |
| Group 5c (normal saline) | Placebo comparator | Other: Normal Saline6-11 months; n=3; 3 doses of normal saline given 8 weeks apart. |
Who may qualify
- Ages
- 6 months to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (17 listed)
- Healthy males and females, based on clinical and laboratory findings
- From the age 6 months to 45 years
- Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or adolescents, children and infants with Z-score of the selected indicator ([weight-for-height], [(height and BMI) for age]) category within ±2SD as detailed in protocol
- Long term (at least one year) or permanent residence in the Bagamoyo town or nearby villages
- Agreement to release medical information and to inform the study doctor concerning contraindications for participation in the study
Key exclusion criteria (14 listed)
- Previous receipt of an investigational malaria vaccine or drug in the last 5 years
- Participation in any other clinical study involving investigational medicinal products within 30 days prior to the onset of the study or during the study period
- History of arrhythmias or prolonged QT-interval or other cardiac disease, or Clinically significant abnormalities in electrocardiogram (ECG) at screening
- Positive family history in a 1st or 2nd degree relative for cardiac disease at age <50 years old
- A history of psychiatric disease
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 VaccineMetabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine) | Biological | Group 1a (PfSPZ Vaccine), Group 1b (PfSPZ Vaccine), Group 2a (PfSPZ Vaccine), Group 2b (PfSPZ Vaccine), Group 3a (PfSPZ Vaccine), Group 3b (PfSPZ Vaccine), Group 4a (PfSPZ Vaccine), Group 4b (PfSPZ Vaccine), Group 5a (PfSPZ Vaccine), Group 5b (PfSPZ Vaccine), Group 5c (PfSPZ Vaccine) |
| Normal Saline0.9% Sodium chloride | Other | Group 1a (normal saline), Group 1b (normal saline), Group 2a (normal saline), Group 2b (normal saline), Group 3a (normal saline), Group 3b (normal saline), Group 4a (normal saline), Group 4b (normal saline), Group 5b (normal saline), Group 5c (normal saline) |
| PfSPZ Challenge (for CHMI)live, infectious, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Challenge) Controlled human malaria infection (CHMI) by direct venous inoculation of 3,200 PfSPZ Challenge | Biological | Group 1a (CHMI controls), Group 1a (PfSPZ Vaccine), Group 1a (normal saline), Group 1b (CHMI controls), Group 1b (PfSPZ Vaccine), Group 1b (normal saline) |
Primary outcome
Incidence and type of Adverse Events
Time frame: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Incidence and type of adverse events (including breakthrough infections), vital signs, clinical laboratory assessments, physical examination findings post first immunization onwards. 1. Occurrence of solicited symptoms during a 7-day surveillance period after vaccination (day of vaccination (Vx) and +7 days post vaccination) 2. Occurrence of unsolicited symptoms during a 28-day surveillance period after each vaccination. 3. Occurrence of serious adverse events during the study period. 4. Occurrence of Pf infection of vaccine type detected at any point after the first vaccination (retrospectively determined).
4 secondary outcomes
Level of Antibodies against Pf proteins in volunteer sera
Time frame: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Inhibitory Capacity of Volunteer Sera against in vitro Sporozoite Invasion of Hepatocytes
Time frame: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Quantitation of cellular immune responses against Pf proteins in volunteers
Time frame: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Whole genome expression profiles of volunteer
Time frame: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
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 15 Oct 2018.
- Derived from this study: PubMed 31782768Jongo SA, Church LWP, Mtoro AT, Schindler T, Chakravarty S, Ruben AJ, Swanson PA, Kassim KR, Mpina M, Tumbo AM, Milando FA, Qassim M, Juma OA, Bakari BM, Simon B, James ER, Abebe Y, Kc N, Saverino E, Fink M, Cosi G, Gondwe L, Studer F, Styers D, Seder RA, Schindler T, Billingsley PF, Daubenberger C, Sim BKL, Tanner M, Richie TL, Abdulla S, Hoffman SL. Increase of Dose Associated With Decrease in Protection Against Controlled Human Malaria Infection by PfSPZ Vaccine in Tanzanian Adults. Clin Infect Dis. 2020 Dec 31;71(11):2849-2857. doi: 10.1093/cid/ciz1152.
- Derived from this study: PubMed 31036014Schindler T, Jongo S, Studer F, Mpina M, Mwangoka G, Mswata S, Ramadhani K, Sax J, Church LWP, Richie TL, Tanner M, Hoffman SL, Abdulla S, Daubenberger C. Two cases of long-lasting, sub-microscopic Plasmodium malariae infections in adults from coastal Tanzania. Malar J. 2019 Apr 29;18(1):149. doi: 10.1186/s12936-019-2787-x.
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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.
Said Jongo, MD, MMED principal investigator
Ifakara Health Institute (IHI), Bagamoyo, Tanzania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PfSPZ Vaccine, Normal Saline and PfSPZ Challenge (for CHMI) in people with Malaria, run by Sanaria Inc. at 1 site in Tanzania.
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 17 inclusion and 14 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 15 Oct 2018. 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 Tanzania. 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 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.
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?
Incidence and type of Adverse Events (time frame: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization). 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 NCT02613520, which also lists 2 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 15 Oct 2018.