- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05604521
A Phase 1 Trial of PfSPZ Vaccine in Healthy Adults to Determine Safety, Tolerability and Efficacy Against Heterologous CHMI
A Randomized, Double-blind, Placebo-controlled, Clinical Trial of a 3-dose, 28-day Regimen of PfSPZ Vaccine in Healthy, Adult Participants to Determine Safety, Tolerability and Efficacy Against Heterologous Plasmodium Falciparum Controlled Human Malaria Infection Conducted 3 or 12 Weeks After Immunization
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
- Randomized, phase 1, double-blind, placebo-controlled clinical trial enrolling healthy adult participants 18-50-years-old living in the US.
- 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.
- 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.
- 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.
- 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.
- Study participation by individuals will last 4 to 6 months (not including screening) depending upon group assignment.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21201
- University of Maryland, Baltimore, Center for Vaccine Development and Global Health
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Group 1a: PfSPZ Vaccine
45 participants will receive 3 doses of 9.0x10^5 PfSPZ Vaccine on Days 1, 8, and 29 with a total dose of 2.7x10^6 PfSPZ Vaccine. Group 1a: Approximately half (22/23) of the volunteers will undergo CHMI 3 weeks after last immunization by exposure to 3.2x10^3 PfSPZ Challenge (7G8). |
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.
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.
|
Active Comparator: Group 1b: PfSPZ Vaccine
45 participants will receive 3 doses of 9.0x10^5 PfSPZ Vaccine on Days 1, 8, and 29 with a total dose of 2.7x10^6 PfSPZ Vaccine. Group 1b: Approximately half (22/23) of the volunteers will undergo CHMI 12 weeks after last immunization by exposure to 3.2x10^3 PfSPZ Challenge (7G8). |
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.
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.
|
Placebo Comparator: Group 2a: Normal Saline Controls
15 participants will receive 3 doses of normal saline on Days 1, 8, and 29. Group 2a: Approximately half (7/8) of the volunteers will undergo CHMI 3 weeks after last immunization by exposure to 3.2x10^3 PfSPZ 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.
0.9% sodium chloride
Other Names:
|
Placebo Comparator: Group 2b: Normal Saline Controls
15 participants will receive 3 doses of normal saline on Days 1, 8, and 29. Group 2b: Approximately half (7/8) of the volunteers will undergo CHMI 12 weeks after last immunization by exposure to 3.2x10^3 PfSPZ 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.
0.9% sodium chloride
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Vaccine efficacy (VE)
Time Frame: 7 days after CHMI up to 28 days
|
VE computed as one minus the estimated risk ratio for Pf malaria (parasitemia) detected by PCR beginning 7 days after CHMI up to 28 days in the modified intention to treat population (proportional efficacy analysis) combining data across the two CHMI timepoints.
|
7 days after CHMI up to 28 days
|
Adverse events
Time Frame: 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.
|
Day of immunization to 28 days post immunization
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
VE for CHMI at 3 weeks
Time Frame: 7 Days after first CHMI up to 28 days
|
VE computed as one minus the estimated risk ratio for Pf malaria (parasitemia) detected by PCR beginning 7 days after CHMI up to 28 days in the modified intention to treat population (proportional efficacy analysis) for CHMI at 3 weeks.
|
7 Days after first CHMI up to 28 days
|
VE for CHMI at 12 weeks
Time Frame: 7 Days after second CHMI up to 28 days
|
VE computed as one minus the estimated risk ratio for Pf malaria (parasitemia) detected by PCR beginning 7 days after CHMI up to 28 days in the modified intention to treat population (proportional efficacy analysis) for CHMI at 12 weeks.
|
7 Days after second CHMI up to 28 days
|
Antibody levels to PfCSP measured by ELISA
Time Frame: Pre vaccination 1 to Day 141
|
Antibody levels to PfCSP measured by ELISA comparing vaccinees to controls, and protected (no parasitemia occurring post CHMI) to non-protected (parasitemia occurring post CHMI) vaccinees.
|
Pre vaccination 1 to Day 141
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Kirsten E Lyke, MD, University of Maryland, Baltimore
Publications and helpful links
General Publications
- Mordmuller B, Sulyok Z, Sulyok M, Molnar Z, Lalremruata A, Calle CL, Bayon PG, Esen M, Gmeiner M, Held J, Heimann HL, Woldearegai TG, Ibanez J, Flugge J, Fendel R, Kreidenweiss A, Kc N, Murshedkar T, Chakravarty S, Riyahi P, Billingsley PF, Church LWP, Richie TL, Sim BKL, Hoffman SL, Kremsner PG. A PfSPZ vaccine immunization regimen equally protective against homologous and heterologous controlled human malaria infection. NPJ Vaccines. 2022 Aug 23;7(1):100. doi: 10.1038/s41541-022-00510-z.
- Lyke KE, Singer A, Berry AA, Reyes S, Chakravarty S, James ER, Billingsley PF, Gunasekera A, Manoj A, Murshedkar T, Laurens MB, Church WP, Garver Baldwin LS, Sedegah M, Banania G, Ganeshan H, Guzman I, Reyes A, Wong M, Belmonte A, Ozemoya A, Belmonte M, Huang J, Villasante E, Sim BKL, Hoffman SL, Richie TL, Epstein JE; Warfighter II Study Team. Multidose Priming and Delayed Boosting Improve Plasmodium falciparum Sporozoite Vaccine Efficacy Against Heterologous P. falciparum Controlled Human Malaria Infection. Clin Infect Dis. 2021 Oct 5;73(7):e2424-e2435. doi: 10.1093/cid/ciaa1294.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- USSPZV7
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malaria
-
University of California, San FranciscoCenters for Disease Control and Prevention; University of Massachusetts, Amherst and other collaboratorsRecruitingPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaLao People's Democratic Republic
-
University of OxfordWellcome Trust; Ministry of public Health AfghanistanCompletedVivax Malaria | Uncomplicated Falciparum MalariaAfghanistan
-
Menzies School of Health ResearchInternational Centre for Diarrhoeal Disease Research, Bangladesh; Addis Ababa... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaEthiopia, Bangladesh, Indonesia
-
Medicines for Malaria VentureAsociacion Civil Selva AmazonicaCompletedPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaPeru
-
Gadjah Mada UniversityMenzies School of Health Research; Eijkman Institute for Molecular Biology; Timika...Completed
-
London School of Hygiene and Tropical MedicineWorld Health Organization; United Nations High Commissioner for Refugees; HealthNet... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaPakistan
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
Research Institute for Tropical Medicine, PhilippinesWorld Health OrganizationCompletedTES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014 (TES)Malaria | Vivax Malaria | Falciparum Malaria | Malaria Recrudescence
-
University of IbadanShin Poong Pharm Co Ltd 161 yoksam-ro, Gangnam-Gu Seoul 135-925, Korea; Institute...CompletedPlasmodium Falciparum Malaria | Uncomplicated Malaria | Malaria FeverNigeria
Clinical Trials on PfSPZ Vaccine
-
Sanaria Inc.German Federal Ministry of Education and Research; German Center for Infection... and other collaboratorsCompleted
-
Sanaria Inc.Swiss Tropical & Public Health Institute; Ifakara Health Institute; Medical Care... and other collaboratorsCompleted
-
Sanaria Inc.Fred Hutchinson Cancer CenterCompleted
-
National Institute of Allergy and Infectious Diseases...Suspended
-
Sanaria Inc.Swiss Tropical & Public Health Institute; Ifakara Health Institute; Government... and other collaboratorsCompleted
-
Sanaria Inc.Swiss Tropical & Public Health Institute; Ifakara Health Institute; Medical Care...CompletedMalaria | Malaria,FalciparumTanzania
-
National Institute of Allergy and Infectious Diseases...Sanaria Inc.; Malaria Research and Training Center, Bamako, MaliCompleted
-
Sanaria Inc.Walter Reed Army Institute of Research (WRAIR); Naval Medical Research Center; Military Infectious Diseases Research Program (MIDRP)Completed
-
Sanaria Inc.Swiss Tropical & Public Health Institute; Ifakara Health Institute; Government... and other collaboratorsCompleted
-
National Institute of Allergy and Infectious Diseases...Malaria Research and Training Center, University of Science Techniques and...Completed