MalariaPhase 1NCT02215707
A Clinical Trial of the PfSPZ Vaccine Administered by Direct Venous Inoculation in Healthy Malaria-Naïve Adults: Heterologous vs. Homologous Controlled Human Malaria Infection and Reduction in Number of Doses
A Phase 1 study testing PfSPZ Vaccine in people with Malaria, run by Sanaria Inc. at 1 site in United States.
Trial summary
This is an open-label evaluation of the safety, tolerability immunogenicity and efficacy of the PfSPZ Vaccine administered by Direct Venous Inoculation (DVI) in healthy, malaria-naïve subjects. There will be 3 groups and a total of 69 subjects (45 immunized subjects and 24 infectivity controls). Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- PfSPZ Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2014to Jun 2015
- 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 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults (male or non-pregnant female) 18 - 45 years of age, inclusive.
- Able and willing to participate for the duration of the study.
- Able and willing to provide written (not proxy) informed consent.
- Women of childbearing potential must agree to use effective means of birth control (e.g. oral or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) during the entire study. Women with a history of surgical or chemical sterilization (e.g. tubal ligation, hysterectomy, other) must provide written documentation of infertility from a Primary Care Provider.
- Willing to refrain from blood donation (except as required in this study) for 3 years following CHMI.
- Agree not to travel to a malaria endemic region during the entire course of the trial.
Who cannot join
- Any history of malaria infection, or travel to a malaria endemic region within 6 months prior to first immunization.
- History of long-term residence (>5 years) in area known to have significant transmission of P. falciparum.
- Has evidence of increased cardiovascular disease risk (defined as > 10%, 5 year risk) as determined by the method of Gaziano [Gaziano, 2008]. Risk factors include sex, age, systolic blood pressure (mm Hg), smoking status, body mass index (BMI, kg/mm2), and reported diabetes status.
- Positive HIV, HBsAg or HCV serology.
- Positive sickle cell screening test.
- An abnormal electrocardiogram, defined as one showing pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm including isolated premature ventricular contractions, but excluding isolated premature atrial contractions; right or left bundle branch block; or advanced (secondary or tertiary) A-V heart block.
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- Current use of systemic immunosuppressant pharmacotherapy.
- Current significant medical condition (cardiovascular, 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) or migraine headache.
- History of psychiatric disorders (such as personality disorders, anxiety disorders, or schizophrenia) or behavioral tendencies (including active alcohol or drug abuse) discovered during the screening process that in the opinion of the investigator would make compliance with the protocol difficult.
- Plan for surgery between enrollment and CHMI.
- Females who are pregnant or nursing, females who plan on becoming pregnant or plan to nurse during the study period.
- Known allergy to any component of the vaccine formulation, history of anaphylactic response to mosquito-bites, or any history of anaphylactic reaction, retinal or visual field changes, or known allergy to anti-malarials including chloroquine phosphate, atovaquone/proguanil (Malarone®), or artemether/lumefantrine (Coartem®)
- Receipt of another investigational vaccine or drug within 30 days prior to the first immunization, or plan to participate in another investigational vaccine/drug research during or within 1 month following participation in this study.
- Receipt of more than three other vaccines within 60 days prior to the screening visit, or plan to receive more than three other vaccines during or within 1 month following participation in this study.
- Personal beliefs that prohibit the receiving of vaccine product containing human serum albumin within the diluent (vaccine recipients only).
- Use or planned use of any drug with anti-malarial activity that would coincide with the periods of immunization or CHMI.
- History of psoriasis or porphyria, which may be exacerbated after treatment with chloroquine.
- Anticipated use of medications known to cause drug reactions with chloroquine, atovaquone-proguanil (Malarone®), or artemether/lumefantrine (Coartem®) such as cimetidine, metoclopramide, antacids, and kaolin.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Walter Reed Army Institute of Research (WRAIR) Clinical Trials Center
Silver Spring, Maryland, 20910
About this study
This is an open-label evaluation of the safety, tolerability immunogenicity and efficacy of the PfSPZ Vaccine administered by Direct Venous Inoculation (DVI) in healthy, malaria-naïve subjects. There will be 3 groups and a total of 69 subjects (45 immunized subjects and 24 infectivity controls).
Read the detailed description
Group 1 (n=15) and Group 2 (n = 15) subjects will receive five doses by DVI of 2.7 x 10^5 PfSPZ per dose (4 doses at 4 week intervals and the 5th dose 8 weeks after the fourth dose). Group 3 (n = 15) will receive 3 doses by DVI of 4. 5 x 10^5 PfSPZ/dose at 8 week intervals. Subjects who complete all immunizations will receive a total 13.5 x 10^5 PfSPZ. Protective efficacy will be assessed by Controlled Human Malaria Infection (CHMI) by exposure to the bites of five Pf-infected mosquitoes. Groups 1 and 3 (n = 30) will undergo each of two CHMIs at the same time with mosquitoes infected with PfSPZ (3D7) (homologous) along with 6 Infectivity Controls. Group 2 will undergo each of two CHMIs separately with mosquitoes infected with PfSPZ (7G8) (heterologous) along with 6 Infectivity Controls. CHMI will occur at approximately 2 to 3 weeks and 24 weeks after the final immunization. Subjects may proceed to CHMI provided they have received no fewer than three scheduled immunizations. Immunized subjects may participate in the second CHMI whether or not they were protected in the first CHMI; boosting of immune responses in CHMI #1 may lead to protection in CHMI #2.
One subject in each of Groups 1 and 2 and 3 subjects in Group 3 will be immunized approximately 24 hours prior to the rest of the group (referred to as "pilot subjects"). For the Group1/Group 2 pilot subjects: the first subject will be immunized and observed on site for a minimum of one hour; at this point, the second subject may be immunized and he/she will also be observed for a minimum of one hour. For Group 3: the three subjects will be immunized sequentially with a minimum 2 hour observation period between subjects (and a two hour observation of the third subject as well). If there are no safety concerns identified in the pilot subjects after 24 hours that trigger the stopping rules, then the rest of subjects in Groups 1, 2 and 3 will be immunized as scheduled. Subjects in Group 3 will receive their first immunization approximately 4 weeks after subjects in Groups 1 and 2 receive their first immunizations. Subjects will be followed for 8 weeks after the last CHMI for safety purposes.
- Conditions
- Malaria
- Being tested
- PfSPZ Vaccine
- Keywords
- PfSPZ Vaccine, Plasmodium falciparum, Malaria, Controlled Human Malaria Infection (CHMI)
- 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
Suspension of metabolically active, non-replicating (live), radiation-attenuated, purified, cryopreserved, aseptic Plasmodium falciparum (Pf) sporozoites (SPZ)
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Group 1: 5 doses of 2.7x10^5 PfSPZ Vaccine; homologous 3D7 CHMI
Grp 1 (n=15) gets 5 doses of 270,000 PfSPZ per dose (4 doses at 4 wk intervals, 2 month delay before 5th dose) by DVI. Grps 1 and 2 start immunizations together.
1 subj in each of Grps 1 and 2 will be immunized approx 24 hrs before rest of grp ("pilot subjects"). For Grp1/Grp 2 pilot subjects: 1st subject will be immunized, observed on site for minimum 1 hr; the 2nd subject may be immunized, will also be observed for minimum 1 hr. If no safety concerns are identified after 24 hrs that trigger the stopping rules, then rest of subjects in Grps 1 and 2 will be immunized.
Approx 3 wks after final dose, Grps 1 and 3 will undergo homologous CHMI (Pf3D7 strain) with 6 Infectivity Controls. Approx 24 wks after last dose, Grps 1 and 3 will undergo 2nd homologous CHMI (3D7) with 6 Infectivity Controls. Subjects will be followed for 8 wks after last CHMI for safety purposes. Receives: Biological: PfSPZ Vaccine |
| Group 2 | Experimental | Grp 2: 5 doses of 2.7x10^5 PfSPZ Vaccine; heterologous 7G8 CHMI
Grp 2 (n=15) gets 5 doses of 270,000 PfSPZ/dose (4 doses at 4wk intervals, 2 month delay before 5th dose) by DVI. Grps 1 / 2 start immunizations together.
1 subj in each of Grps 1 / 2 will be immunized approx 24 hrs before rest of grp ("pilot subjects"). For Grp1/ 2 pilot subj: 1st subj will be immunized, observed on site for min 1 hr; 2nd subj may be immunized, will also be observed for min 1 hr. If no safety concerns after 24 hrs that trigger stopping rules, then rest of Grps 1 / 2 will be immunized.
Approx 3 wks after final dose, Grps 1/3 have homologous CHMI; 2-3 days later, Grp 2 will undergo heterologous CHMI (Pf7G8) with 6 Infectivity Controls. Approx 24 wks after last dose, Grps 1/3 have 2nd homologous CHMI; 2-3 days later, Grp 2 will undergo 2nd heterologous CHMI (7G8 strain) with 6 Infectivity Controls. Subj will be followed for 8 wks after last CHMI for safety purposes. Receives: Biological: PfSPZ Vaccine |
| Group 3 | Experimental | Grp 3 (n=15) will receive 3 doses by DVI of 450,000 PfSPZ/dose (of PfSPZ Vaccine) at 8 wk intervals (starting approx. 4 wks after Grps 1 and 2 get 1st immunization).
3 subjects in Grp 3 will be immunized approx 24 hrs prior to rest of grp ("pilot subjects"). The 3 subjects will be immunized sequentially with min 2 hr observation period between subjects (and a 2 hr observation of 3rd subject as well). If no safety concerns identified in pilot subjects after 24 hours that trigger the stopping rules, the rest of subjects in Grp 3 will be immunized as scheduled.
Approx 3 wks after final dose, Grps 1 and 3 will undergo homologous CHMI (3D7 strain) with 6 Infectivity Controls. Approx 24 wks after last dose, Grps 1 and 3 will undergo 2nd homologous CHMI (3D7) with 6 Infectivity Controls. Subjects will be followed for 8 wks after last CHMI for safety purposes. Receives: Biological: PfSPZ Vaccine |
| CHMI Controls.1 | No intervention | n = 6, infectivity controls for 1st homologous CHMI (3D7) occurring approximately 3 weeks after final immunization of Groups 1 and 3. This group does not receive the PfSPZ Vaccine. |
| CHMI Controls.2 | No intervention | n = 6, infectivity controls for 1st heterologous CHMI (7G8) occurring approximately 3 weeks after final immunization of Group 2. This group does not receive the PfSPZ Vaccine. |
| CHMI Controls.3 | No intervention | n = 6, infectivity controls for 2nd homologous CHMI (3D7) occurring approximately 24 weeks after final immunization of Groups 1 and 3. This group does not receive the PfSPZ Vaccine. |
| CHMI Controls.4 | No intervention | n = 6, infectivity controls for 2nd heterologous CHMI (7G8) occurring approximately 24 weeks after final immunization of Group 2. This group does not receive the PfSPZ Vaccine. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and type of adverse events (including breakthrough infections), vital signs, clinical laboratory assessments, physical examination findings.
Measured: Day of immunization through week 52
Evidence of vaccine-mediated protection against CHMI 2-3 weeks and 24 weeks after last immunization in Groups 1, 2, and 3, preventing blood stage infection for 28 days (as detected by blood smear analysis) following CHMI.
Measured: 28 days post each CHMI
Secondary outcomes (10)
Antibody titers to Pf proteins by ELISA
Assess the cellular and antibody responses induced by the PfSPZ Vaccine to determine whether any immune response(s) correlate with protection.
Measured: Screening until week 52
Antibody titers to Pf parasite stages by IFA
Assess the cellular and antibody responses induced by the PfSPZ Vaccine to determine whether any immune response(s) correlate with protection.
Measured: Screening until week 52
Capacity to inhibit sporozoite invasion of hepatocytes in vitro by ISI assay
Assess the cellular and antibody responses induced by the PfSPZ Vaccine to determine whether any immune response(s) correlate with protection.
Measured: Screening until week 52
Analysis of antibodies to any of the thousands of proteins in the Pf proteome using proteome array chips
Assess the cellular and antibody responses induced by the PfSPZ Vaccine to determine whether any immune response(s) correlate with protection.
Measured: Screening until week 52
Multi-channel intracellular staining (ICS) analysis by flow cytometry against PfSPZ and synthetic peptides and recombinant proteins from defined Pf proteins
Assess the cellular and antibody responses induced by the PfSPZ Vaccine to determine whether any immune response(s) correlate with protection.
Measured: Screening until week 52
Analysis of ELISpot responses in response to stimulation with PfSPZ and synthetic peptides and recombinant proteins from defined Pf proteins
Assess the cellular and antibody responses induced by the PfSPZ Vaccine to determine whether any immune response(s) correlate with protection.
Measured: Screening until week 52
Analysis of T cell receptor studies
Assess the cellular and antibody responses induced by the PfSPZ Vaccine to determine whether any immune response(s) correlate with protection.
Measured: Screening until week 52
B cell/plasmablast studies
Assess the cellular and antibody responses induced by the PfSPZ Vaccine to determine whether any immune response(s) correlate with protection.
Measured: Screening until week 52
Human gene expression profiling focusing on immune response genes
Assess the cellular and antibody responses induced by the PfSPZ Vaccine to determine whether any immune response(s) correlate with protection.
Measured: Screening until week 52
Luminex or Luminex type studies to assess multiple cytokines and other host molecules
Assess the cellular and antibody responses induced by the PfSPZ Vaccine to determine whether any immune response(s) correlate with protection.
Measured: Screening until week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2014 (estimated)
- Study startJun 2014
- Primary completionApr 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanaria Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Naval Medical Research Center, Walter Reed Army Institute of Research (WRAIR), Military Infectious Diseases Research Program (MIDRP)
- Responsible party
- Sponsor
- Investigators
- Judith Epstein, MD, Principal investigator, Naval Medical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02215707
- Sponsor's protocol ID
- WRAIR #2080
- Other IDs
- NMRC.2014.004, WRAIR #2080
- Status last verified
- Nov 2015
- First submitted
- 1 Aug 2014
- Last updated
- 29 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Epstein JE, Paolino KM, Richie TL, Sedegah M, Singer A, Ruben AJ, Chakravarty S, Stafford A, Ruck RC, Eappen AG, Li T, Billingsley PF, Manoj A, Silva JC, Moser K, Nielsen R, Tosh D, Cicatelli S, Ganeshan H, Case J, Padilla D, Davidson S, Garver L, Saverino E, Murshedkar T, Gunasekera A, Twomey PS, Reyes S, Moon JE, James ER, Kc N, Li M, Abot E, Belmonte A, Hauns K, Belmonte M, Huang J, Vasquez C, Remich S, Carrington M, Abebe Y, Tillman A, Hickey B, Regules J, Villasante E, Sim BKL, Hoffman SL. Protection against Plasmodium falciparum malaria by PfSPZ Vaccine. JCI Insight. 2017 Jan 12;2(1):e89154. doi: 10.1172/jci.insight.89154.
PubMed 28097230
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial of the PfSPZ Vaccine Administered by Direct Venous Inoculation in Healthy Malaria-Naïve Adults: Heterologous vs. Homologous Controlled Human Malaria Infection and Reduction in Number of Doses
- ClinicalTrials.gov ID
- NCT02215707
- Acronym / sponsor ID
- WRAIR #2080
- Conditions
- Malaria
- Keywords
- PfSPZ Vaccine, Plasmodium falciparum, Malaria, Controlled Human Malaria Infection (CHMI)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Sanaria Inc.Industry (pharma, biotech, devices)
- Collaborators
- Naval Medical Research Center, Walter Reed Army Institute of Research (WRAIR), Military Infectious Diseases Research Program (MIDRP)
- Study start
- Jun 2014
- Primary completion
- Apr 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 13 Aug 2014 (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 is an open-label evaluation of the safety, tolerability immunogenicity and efficacy of the PfSPZ Vaccine administered by Direct Venous Inoculation (DVI) in healthy, malaria-naïve subjects. There will be 3 groups and a total of 69 subjects (45 immunized subjects and 24 infectivity controls).
Detailed description
Group 1 (n=15) and Group 2 (n = 15) subjects will receive five doses by DVI of 2.7 x 10^5 PfSPZ per dose (4 doses at 4 week intervals and the 5th dose 8 weeks after the fourth dose). Group 3 (n = 15) will receive 3 doses by DVI of 4. 5 x 10^5 PfSPZ/dose at 8 week intervals. Subjects who complete all immunizations will receive a total 13.5 x 10^5 PfSPZ. Protective efficacy will be assessed by Controlled Human Malaria Infection (CHMI) by exposure to the bites of five Pf-infected mosquitoes. Groups 1 and 3 (n = 30) will undergo each of two CHMIs at the same time with mosquitoes infected with PfSPZ (3D7) (homologous) along with 6 Infectivity Controls. Group 2 will undergo each of two CHMIs separately with mosquitoes infected with PfSPZ (7G8) (heterologous) along with 6 Infectivity Controls. CHMI will occur at approximately 2 to 3 weeks and 24 weeks after the final immunization. Subjects may proceed to CHMI provided they have received no fewer than three scheduled immunizations. Immunized subjects may participate in the second CHMI whether or not they were protected in the first CHMI; boosting of immune responses in CHMI #1 may lead to protection in CHMI #2.
One subject in each of Groups 1 and 2 and 3 subjects in Group 3 will be immunized approximately 24 hours prior to the rest of the group (referred to as "pilot subjects"). For the Group1/Group 2 pilot subjects: the first subject will be immunized and observed on site for a minimum of one hour; at this point, the second subject may be immunized and he/she will also be observed for a minimum of one hour. For Group 3: the three subjects will be immunized sequentially with a minimum 2 hour observation period between subjects (and a two hour observation of the third subject as well). If there are no safety concerns identified in the pilot subjects after 24 hours that trigger the stopping rules, then the rest of subjects in Groups 1, 2 and 3 will be immunized as scheduled. Subjects in Group 3 will receive their first immunization approximately 4 weeks after subjects in Groups 1 and 2 receive their first immunizations. Subjects will be followed for 8 weeks after the last CHMI for safety purposes.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Biological: PfSPZ VaccineGroup 1: 5 doses of 2.7x10^5 PfSPZ Vaccine; homologous 3D7 CHMI Grp 1 (n=15) gets 5 doses of 270,000 PfSPZ per dose (4 doses at 4 wk intervals, 2 month delay before 5th dose) by DVI. Grps 1 and 2 start immunizations together. 1 subj in each of Grps 1 and 2 will be immunized approx 24 hrs before rest of grp ("pilot subjects"). For Grp1/Grp 2 pilot subjects: 1st subject will be immunized, observed on site for minimum 1 hr; the 2nd subject may be immunized, will also be observed for minimum 1 hr. If no safety concerns are identified after 24 hrs that trigger the stopping rules, then rest of subjects in Grps 1 and 2 will be immunized. Approx 3 wks after final dose, Grps 1 and 3 will undergo homologous CHMI (Pf3D7 strain) with 6 Infectivity Controls. Approx 24 wks after last dose, Grps 1 and 3 will undergo 2nd homologous CHMI (3D7) with 6 Infectivity Controls. Subjects will be followed for 8 wks after last CHMI for safety purposes. |
| Group 2 | Experimental | Biological: PfSPZ VaccineGrp 2: 5 doses of 2.7x10^5 PfSPZ Vaccine; heterologous 7G8 CHMI Grp 2 (n=15) gets 5 doses of 270,000 PfSPZ/dose (4 doses at 4wk intervals, 2 month delay before 5th dose) by DVI. Grps 1 / 2 start immunizations together. 1 subj in each of Grps 1 / 2 will be immunized approx 24 hrs before rest of grp ("pilot subjects"). For Grp1/ 2 pilot subj: 1st subj will be immunized, observed on site for min 1 hr; 2nd subj may be immunized, will also be observed for min 1 hr. If no safety concerns after 24 hrs that trigger stopping rules, then rest of Grps 1 / 2 will be immunized. Approx 3 wks after final dose, Grps 1/3 have homologous CHMI; 2-3 days later, Grp 2 will undergo heterologous CHMI (Pf7G8) with 6 Infectivity Controls. Approx 24 wks after last dose, Grps 1/3 have 2nd homologous CHMI; 2-3 days later, Grp 2 will undergo 2nd heterologous CHMI (7G8 strain) with 6 Infectivity Controls. Subj will be followed for 8 wks after last CHMI for safety purposes. |
| Group 3 | Experimental | Biological: PfSPZ VaccineGrp 3 (n=15) will receive 3 doses by DVI of 450,000 PfSPZ/dose (of PfSPZ Vaccine) at 8 wk intervals (starting approx. 4 wks after Grps 1 and 2 get 1st immunization). 3 subjects in Grp 3 will be immunized approx 24 hrs prior to rest of grp ("pilot subjects"). The 3 subjects will be immunized sequentially with min 2 hr observation period between subjects (and a 2 hr observation of 3rd subject as well). If no safety concerns identified in pilot subjects after 24 hours that trigger the stopping rules, the rest of subjects in Grp 3 will be immunized as scheduled. Approx 3 wks after final dose, Grps 1 and 3 will undergo homologous CHMI (3D7 strain) with 6 Infectivity Controls. Approx 24 wks after last dose, Grps 1 and 3 will undergo 2nd homologous CHMI (3D7) with 6 Infectivity Controls. Subjects will be followed for 8 wks after last CHMI for safety purposes. |
| CHMI Controls.1 | No intervention | –n = 6, infectivity controls for 1st homologous CHMI (3D7) occurring approximately 3 weeks after final immunization of Groups 1 and 3. This group does not receive the PfSPZ Vaccine. |
| CHMI Controls.2 | No intervention | –n = 6, infectivity controls for 1st heterologous CHMI (7G8) occurring approximately 3 weeks after final immunization of Group 2. This group does not receive the PfSPZ Vaccine. |
| CHMI Controls.3 | No intervention | –n = 6, infectivity controls for 2nd homologous CHMI (3D7) occurring approximately 24 weeks after final immunization of Groups 1 and 3. This group does not receive the PfSPZ Vaccine. |
| CHMI Controls.4 | No intervention | –n = 6, infectivity controls for 2nd heterologous CHMI (7G8) occurring approximately 24 weeks after final immunization of Group 2. This group does not receive the PfSPZ Vaccine. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Healthy adults (male or non-pregnant female) 18 - 45 years of age, inclusive.
- Able and willing to participate for the duration of the study.
- Able and willing to provide written (not proxy) informed consent.
- Women of childbearing potential must agree to use effective means of birth control (e.g. oral or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) during the entire study. Women with a history of surgical or chemical sterilization (e.g. tubal ligation, hysterectomy, other) must provide written documentation of infertility from a Primary Care Provider.
- Willing to refrain from blood donation (except as required in this study) for 3 years following CHMI.
Key exclusion criteria (21 listed)
- Any history of malaria infection, or travel to a malaria endemic region within 6 months prior to first immunization.
- History of long-term residence (>5 years) in area known to have significant transmission of P. falciparum.
- Has evidence of increased cardiovascular disease risk (defined as > 10%, 5 year risk) as determined by the method of Gaziano [Gaziano, 2008]. Risk factors include sex, age, systolic blood pressure (mm Hg), smoking status, body mass index (BMI, kg/mm2), and reported diabetes status.
- Positive HIV, HBsAg or HCV serology.
- Positive sickle cell screening test.
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 VaccineSuspension of metabolically active, non-replicating (live), radiation-attenuated, purified, cryopreserved, aseptic Plasmodium falciparum (Pf) sporozoites (SPZ) | Biological | Group 1, Group 2, Group 3 |
Primary outcome
Incidence and type of adverse events (including breakthrough infections), vital signs, clinical laboratory assessments, physical examination findings.
Time frame: Day of immunization through week 52
Evidence of vaccine-mediated protection against CHMI 2-3 weeks and 24 weeks after last immunization in Groups 1, 2, and 3, preventing blood stage infection for 28 days (as detected by blood smear analysis) following CHMI.
Time frame: 28 days post each CHMI
10 secondary outcomes
Antibody titers to Pf proteins by ELISA
Time frame: Screening until week 52
Antibody titers to Pf parasite stages by IFA
Time frame: Screening until week 52
Capacity to inhibit sporozoite invasion of hepatocytes in vitro by ISI assay
Time frame: Screening until week 52
Analysis of antibodies to any of the thousands of proteins in the Pf proteome using proteome array chips
Time frame: Screening until week 52
Multi-channel intracellular staining (ICS) analysis by flow cytometry against PfSPZ and synthetic peptides and recombinant proteins from defined Pf proteins
Time frame: Screening until week 52
Analysis of ELISpot responses in response to stimulation with PfSPZ and synthetic peptides and recombinant proteins from defined Pf proteins
Time frame: Screening until week 52
Analysis of T cell receptor studies
Time frame: Screening until week 52
B cell/plasmablast studies
Time frame: Screening until week 52
Human gene expression profiling focusing on immune response genes
Time frame: Screening until week 52
Luminex or Luminex type studies to assess multiple cytokines and other host molecules
Time frame: Screening until week 52
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 29 Jun 2018.
- Results publication: PubMed 28097230Epstein JE, Paolino KM, Richie TL, Sedegah M, Singer A, Ruben AJ, Chakravarty S, Stafford A, Ruck RC, Eappen AG, Li T, Billingsley PF, Manoj A, Silva JC, Moser K, Nielsen R, Tosh D, Cicatelli S, Ganeshan H, Case J, Padilla D, Davidson S, Garver L, Saverino E, Murshedkar T, Gunasekera A, Twomey PS, Reyes S, Moon JE, James ER, Kc N, Li M, Abot E, Belmonte A, Hauns K, Belmonte M, Huang J, Vasquez C, Remich S, Carrington M, Abebe Y, Tillman A, Hickey B, Regules J, Villasante E, Sim BKL, Hoffman SL. Protection against Plasmodium falciparum malaria by PfSPZ Vaccine. JCI Insight. 2017 Jan 12;2(1):e89154. doi: 10.1172/jci.insight.89154.
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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.
Judith Epstein, MD principal investigator
Naval Medical Research Center
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 in people with Malaria, run by Sanaria Inc. at 1 site in United States.
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 6 inclusion and 21 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 29 Jun 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 United States. 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. 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 (including breakthrough infections), vital signs, clinical laboratory assessments, physical examination findings. (time frame: Day of immunization through week 52). The study lists 2 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 NCT02215707, which also lists 1 linked publication.
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 29 Jun 2018.