Malaria, Malaria,Falciparum
Conditions
Keywords
Malaria, Plasmodium falciparum, Sporozoites, PfSPZ Vaccine
Brief summary
USSPZV7 is a randomized, phase 1, double-blind, placebo-controlled trial of Sanaria® PfSPZ Vaccine administered on Days 1, 8 and 29 by direct venous inoculation (DVI) to assess safety, tolerability, immunogenicity, and vaccine efficacy (VE) against heterologous controlled human malaria infection (CHMI) with the 7G8 clone of Plasmodium falciparum (Pf) conducted at 3 or 12 weeks after the third immunization. The trial is designed to determine if individuals living in a non-malaria endemic area such as the United States (US) are protected against heterologous CHMI conducted at these time points.
Detailed description
1. Randomized, phase 1, double-blind, placebo-controlled clinical trial enrolling healthy adult participants 18-50-years-old living in the US. 2. The trial is designed to measure safety, tolerability, immunogenicity and VE against heterologous controlled human malaria vaccine conducted at 3 or 12 weeks after vaccination. 3. Participants will be randomized to two study groups, vaccine and placebo, in a 3:1 ratio. Treatment assignment will be double blind; however, whether a given participant will be receiving CHMI at 3 or 12 weeks will not be blind. 4. Bias will be minimized by the randomized, double-blind design and by the inability to distinguish vaccine or placebo based on appearance, tolerability or other characteristics discernable by clinical staff or study participants. 5. The study will take approximately 6 to 8 months to complete, not including 2-3 months of recruitment. The period of follow-up for each immunized participant and placebo controls is through 8 weeks post-CHMI. 6. Study participation by individuals will last 4 to 6 months (not including screening) depending upon group assignment.
Interventions
BIOLOGICALPfSPZ Vaccine
PfSPZ vaccine consists of radiation-attenuated, aseptic, purified Plasmodium falciparum (NF54) sporozoites (SPZ) cryopreserved in liquid nitrogen vapor phase (LNVP) at -150C to - 196C. PfSPZ Vaccine is composed of PfSPZ derived from the NF54 strain of Pf, which is thought to be from West Africa. PfSPZ Vaccine is diluted in phosphate buffered saline (PBS) with human serum albumin (HSA) to achieve the correct dosage and is administered by DVI.
BIOLOGICALPfSPZ Challenge (7G8)
PfSPZ Challenge (7G8) is similar to PfSPZ Vaccine but has not been attenuated by radiation and is therefore infectious.PfSPZ Challenge (7G8) is composed of PfSPZ derived from the 7G8 clone of Pf, which is from Brazil.
OTHERNormal Saline
0.9% sodium chloride
Sponsors
University of Maryland, Baltimore
National Institute of Allergy and Infectious Diseases (NIAID)
Sanaria Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adults (male or non-pregnant female) 18 to 50 years of age. * Able and willing to participate for the duration of the study. * Able and willing to provide written informed consent and satisfactorily complete a test of understanding with a passing score \>80%. * Physical examination and laboratory results without clinically significant findings. * 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). * Willing to refrain from blood donation for 3 years following CHMI. * Agree not to travel to a malaria endemic region during the trial.
Exclusion criteria
* Unable to provide informed consent including inability to pass the test of understanding, which is written in English for the US-based study sites. * Receipt of a malaria vaccine in a prior clinical trial. * History of a splenectomy or sickle cell disease. * History of a neurologic disorder (including non-febrile seizures or complex febrile seizures) or formal history of migraine headache. * Current use of systemic immunosuppressant pharmacotherapy. * Receipt of a live vaccine within 4 weeks of first immunization or of 3 or more non-live vaccines within 2 weeks of first immunization. * Women who are breast-feeding, pregnant or planning to become pregnant during the study period. * Known allergy to atovaquone-proguanil (Malarone®), artemether-lumefantrine (Coartem®), or any component of the investigational products. * A history of malaria in the 2 years prior to screening. * Participation in any study involving investigational vaccine or drug within 4 weeks prior to enrollment that in the estimation of the site PI might adversely affect the individual's safety or the quality of data to be collected. * Evidence of increased cardiovascular disease risk; defined as \>10% five-year risk by nonlaboratory method. * Plan to participate in another investigational vaccine/drug research during the study. * Plan for major surgery between enrollment until 28 days post-CHMI. * Use or planned use of any drug with anti-malarial activity that would precede or coincide with malaria challenge or vaccination. * Anticipated use of medications known to cause drug reactions with atovaquone-proguanil or artemether-lumefantrine such as cimetidine, metoclopramide, antacids, and kaolin. * Positive HBsAg or positive HIV or HCV testing consistent with active infection. * An abnormal electrocardiogram, defined as one showing pathologic Q waves and significant STT 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; or other clinically significant abnormalities on the electrocardiogram as determined by the consulting cardiologist. * Any clinically significant deviation from the normal range in biochemistry or hematology tests measured at screening and not resolving. * Any medical, psychiatric, social, behavioral or occupational condition or situation (including active alcohol or drug abuse) that, in the judgment of the site PI, impairs the volunteer's ability to give informed consent, increases the risk to the participant of participation in the study, affects the ability of the participant to participate fully in the study, or might negatively impact the quality, consistency, integrity or interpretation of data derived from their participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Day of immunization to 28 days post immunization | The differences in proportions of vaccinees compared to controls experiencing related moderate, severe, or serious solicited and unsolicited adverse events and laboratory abnormalities after vaccination. |
Countries
United States
Participant flow
Recruitment details
Altogether, 72 persons were screened, 31 received immunizations, 15 were screen failures, 4 were eligible but yet not enrolled, and 22 were still being evaluated when the study was terminated.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: PfSPZ Vaccine N=24; received at least 1 dose of vaccine. | 24 |
| Group 2: Normal Saline Placebo N=7; received normal saline placebo | 7 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Trial terminated early due to an extended gap between the 2nd and 3rd doses (3rd dose not given). | 23 | 7 |
Baseline characteristics
| Characteristic | Group 1: PfSPZ Vaccine | Group 2: Normal Saline Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 7 Participants | 31 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 6 Participants | 24 Participants |
| Region of Enrollment United States | 24 Participants | 7 Participants | 31 Participants |
| Sex: Female, Male Female | 10 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Male | 14 Participants | 4 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 7 |
| other Total, other adverse events | 17 / 24 | 7 / 7 |
| serious Total, serious adverse events | 0 / 24 | 0 / 7 |
Outcome results
Primary
Adverse Events
The differences in proportions of vaccinees compared to controls experiencing related moderate, severe, or serious solicited and unsolicited adverse events and laboratory abnormalities after vaccination.
Time frame: Day of immunization to 28 days post immunization
Population: 24 participants received a 1st dose and 23 participants received a 2nd dose of vaccine, and 7 participants received 2 doses of placebo. Due to early study termination, we measured outcome variables for which data were available: proportion of participants experiencing local solicited AEs, systemic solicited AEs and related unsolicited AEs.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: PfSPZ Vaccine | Adverse Events | 17 Participants |
| Group 2: Normal Saline Placebo | Adverse Events | 7 Participants |
Comparison: Null hypothesis: There is no statistically significant difference between the vaccine and control groups in the proportion of participants experiencing any local solicited AEs after any vaccination.p-value: 0.3944Fisher Exact
Comparison: Null hypothesis: There is no statistically significant difference between the vaccine and control groups in the proportion of participants experiencing any systemic solicited AEs after any vaccination.p-value: 0.3717Fisher Exact
Comparison: Null hypothesis: There is no statistically significant difference between the vaccine and control groups in the proportion of participants experiencing any related unsolicited AEs after any vaccination.p-value: 1Fisher Exact