ACTIVE_NOT_RECRUITING

First-in-Human PfSPZ-LARC2 Vaccination/CHMI

Conditions

Malaria Artemether/lumefantrine (Coartem(R))Atovaquone/proguanil (Malarone(R))CHMI controlled First-in-human Plasmodium falciparum Saline Sanaria(R) PfSPZ Challenge (7G8)Sanaria(R) PfSPZ-LARC2 Sentinel Vaccine

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This randomized, double-blind, placebo-controlled, Phase 1 trial will enroll up to 22 malaria-naïve, adult participants to test safety, tolerability, immunogenicity, and efficacy of the genetically attenuated Plasmodium falciparum sporozoite vaccine (PfSPZ-LARC2) Vaccine. PfSPZ-LARC2 Vaccine is a late-arresting, replication-competent whole Plasmodium falciparum sporozoite product. We hypothesize that the PfSPZ-LARC2 Vaccine will be safe from breakthrough infection by virtue of deletion of two key parasite genes Mei2 and LINUP and may be more immunogenic and protective than previously tested early arresting sporozoite vaccines. The primary objective is to assess the tolerability and safety of administration of PfSPZ-LARC2 Vaccine, with special attention to the adequacy of attenuation.

Official Title

A Randomized, Double-Blind, Placebo-Controlled Phase 1 Trial to Evaluate the Safety, Tolerability, Immunogenicity, and Efficacy of Sanaria(R) PfSPZ-LARC2 Vaccine, a Late-Arresting, Replication-Competent, Genetically Attenuated Plasmodium Falciparum Vaccine by Controlled Human Malaria Infection in Malaria-Naïve Healthy Adults

Quick Facts

Study Start:2025-07-23

Study Completion:2027-03-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06735209

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 45 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
1. Provides written informed consent prior to the initiation of any study procedures. 2. Able to understand and agrees to adhere to all planned study procedures and be available for all study visits. 3. Male or non-pregnant female, 18 to 45 years of age (inclusive) at time of enrollment. 4. BMI 18.0-35.0 kg/m\^2 at screening. 5. Females of childbearing potential\* must agree to use or have practiced true abstinence\\ or use at least one acceptable primary form of contraception\\\,\\\\,\\\\\ Note: These criteria are applicable to females in a heterosexual relationship and child-bearing potential (i.e., the criteria do not apply to participants in a same sex relationship). * Must use at least one acceptable primary form of contraception for at least 30 days prior to the enrollment visit (Visit 1) and at least one acceptable primary form of contraception for 60 days after the last vaccination or until 28 days post-CHMI, whichever is later. * If the participant is treated with Coartem(R) (artemether/lumefantrine - second-line anti-malarial treatment in this study), participants must agree to add an additional barrier method of contraception during treatment. 6. Females of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to enrollment. 7. Males of childbearing potential: use condoms with a female partner of childbearing potential from their enrollment visit (Visit 1), to 60 days after last vaccination or 28 days post-Controlled Human Malaria Infection (CHMI), whichever is later.\,\\* 8. Male participants agree to refrain from sperm donation from the time of first vaccination until 60 days after the last vaccination or until 28 days post-CHMI, whichever is later. 9. In good health\* 10. Oral temperature is less than 100.4 degrees F (38 degrees C). 11. Resting pulse, no greater than 100 beats per minute. 12. Systolic BP is \</=140 mm Hg. 13. Clinical screening laboratory evaluations (White Blood Cell Count \[WBC\], Hemoglobin \[Hgb\], Platelet Count\[PLTs\], Absolute Neutrophil Count\[ANC\], Absolute Lymphocyte Count \[ALC\], Alanine Aminotransferase \[ALT\], Aspartate Aminotransferase \[AST\], creatinine, glucose) are within acceptable normal local reference ranges\* \*A low creatinine, AST, or ALT value below the normal range are acceptable for trial inclusion as such results are not considered to be clinically significant. If laboratory values are within the normal local reference ranges and Grade 1 (mild) grading criteria are met, these abnormal laboratory values are acceptable for trial inclusion if they are not deemed to be clinically significant by the PI and/or medically trained study clinician listed on Form 1572. 14. Must agree to refrain from donating blood or plasma during the study (outside of this study). 15. Willing to refrain from blood donation for 3 years following CHMI. 16. Agree not to travel to a malaria endemic region until 28 days after CHMI. 17. Willing to take anti-malarial medicines if deemed necessary per protocol or at investigator discretion. 18. Passing score on written Assessment of Understanding (minimum passing score of 80 percent required for participation and one repeat testing is allowed if necessary).	1. Unable to provide informed consent including inability to pass the test of understanding. 2. Receipt of a malaria vaccine in a prior clinical trial. 3. History of malaria infection within 2 years prior to study participation. 4. History of a splenectomy or sickle cell disease. 5. History of a non-febrile seizures or complex febrile seizures. 6. Current use of systemic immunosuppressant/immunomodulatory pharmacotherapy. 7. Receipt of a live vaccine within 4 weeks of first vaccination or of 3 or more non-live vaccines within 2 weeks of first vaccination. 8. Receipt of a live vaccine within 4 weeks of CHMI for infectivity controls or of 3 or more non-live vaccines within 2 weeks of CHMI for infectivity controls. 9. Females who are breast-feeding, pregnant or planning to become pregnant during the study period. 10. Known allergy to atovaquone-proguanil (Malarone(R)), artemether-lumefantrine (Coartem(R)), or any component of the investigational products. 11. History of anaphylaxis or other life-threatening reaction to a vaccine. 12. Participation in any study of investigational vaccine/drug \<4 weeks before enrollment that in the estimation of the site PI might adversely affect safety or data quality. 13. Evidence of increased cardiovascular disease risk (defined as \>10 percent five-year risk by non-laboratory method or prior history of myocardial infarction or myocarditis. 14. Plan to participate in another investigational vaccine/drug research during the study. 15. Plan for major surgery between enrollment until 28 days post-CHMI. 16. Current or anticipated use of any drug with anti-malarial activity that would precede or coincide with malaria challenge or vaccination\* \Such medications include but are not limited to doxycycline, tetracycline, erythromycin, clindamycin, azithromycin, trimethoprim/sulfamethoxazole, atovaquone, proguanil, pyrimethamine, quinine, tafenoquine, primaquine, artemisinin derivatives, chloroquine and other 4-amino and 8-aminoquinolines. 17. Current or anticipated use of medications known to cause drug reactions with atovaquone-proguanil or artemether-lumefantrine (e.g., cimetidine, metoclopramide, antacids, and kaolin). 18. Current or anticipated use of medications associated with moderate or high risk for prolonging the QT interval\ 19. Current or anticipated use of medications that undergo clinically significant metabolism via the cytochrome enzyme CYP2D6.\* 20. Current or anticipated use of medications that undergo clinically significant metabolism via CYP3A4 or are clinically significant inhibitors or strong inducers of CYP3A4.\,\\* 21. Current or anticipated use of medications that have a clinically significant mixed effect on CYP3A4 (e.g., ritonavir, efavirenz). 22. Known disturbances of the electrolyte balance (e.g., hypokalemia or hypomagnesemia). 23. Positive human immunodeficiency virus (HIV) or hepatitis B surface antigen (HbsAg) serology, or hepatitis C virus (HCV) seropositivity with evidence of HCV viremia. 24. Positive Plasmodium 18S rRNA Reverse Transcription Polymerase Chain Reaction (RT-PCR) at baseline. 25. An abnormal electrocardiogram\* 26. History or family history of prolongation of the QT interval. 27. Any other exclusionary medical, psychiatric, social, behavioral or occupational condition or situation as judged by the site PI intended to ensure participant safety and quality of the trial\* \*These kind of exclusionary medical, psychiatric, social, behavioral or occupational condition(s) or situation(s) (including active alcohol or drug abuse) include aspects that could impair the participant's ability to give informed consent, increase the risk to the participant of participation in the study, affect the ability of the participant to participate fully in the study, or negatively impact the quality, consistency, integrity or interpretation of data derived from their participation in the study.

Inclusion Criteria

Exclusion Criteria

1. Provides written informed consent prior to the initiation of any study procedures.
2. Able to understand and agrees to adhere to all planned study procedures and be available for all study visits.
3. Male or non-pregnant female, 18 to 45 years of age (inclusive) at time of enrollment.
4. BMI 18.0-35.0 kg/m\^2 at screening.
5. Females of childbearing potential\* must agree to use or have practiced true abstinence\*\* or use at least one acceptable primary form of contraception\*\*\*,\*\*\*\*,\*\*\*\*\* Note: These criteria are applicable to females in a heterosexual relationship and child-bearing potential (i.e., the criteria do not apply to participants in a same sex relationship).
* Must use at least one acceptable primary form of contraception for at least 30 days prior to the enrollment visit (Visit 1) and at least one acceptable primary form of contraception for 60 days after the last vaccination or until 28 days post-CHMI, whichever is later.
* If the participant is treated with Coartem(R) (artemether/lumefantrine - second-line anti-malarial treatment in this study), participants must agree to add an additional barrier method of contraception during treatment.
6. Females of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to enrollment.
7. Males of childbearing potential: use condoms with a female partner of childbearing potential from their enrollment visit (Visit 1), to 60 days after last vaccination or 28 days post-Controlled Human Malaria Infection (CHMI), whichever is later.\*,\*\*
8. Male participants agree to refrain from sperm donation from the time of first vaccination until 60 days after the last vaccination or until 28 days post-CHMI, whichever is later.
9. In good health\*
10. Oral temperature is less than 100.4 degrees F (38 degrees C).
11. Resting pulse, no greater than 100 beats per minute.
12. Systolic BP is \</=140 mm Hg.
13. Clinical screening laboratory evaluations (White Blood Cell Count \[WBC\], Hemoglobin \[Hgb\], Platelet Count\[PLTs\], Absolute Neutrophil Count\[ANC\], Absolute Lymphocyte Count \[ALC\], Alanine Aminotransferase \[ALT\], Aspartate Aminotransferase \[AST\], creatinine, glucose) are within acceptable normal local reference ranges\* \*A low creatinine, AST, or ALT value below the normal range are acceptable for trial inclusion as such results are not considered to be clinically significant. If laboratory values are within the normal local reference ranges and Grade 1 (mild) grading criteria are met, these abnormal laboratory values are acceptable for trial inclusion if they are not deemed to be clinically significant by the PI and/or medically trained study clinician listed on Form 1572.
14. Must agree to refrain from donating blood or plasma during the study (outside of this study).
15. Willing to refrain from blood donation for 3 years following CHMI.
16. Agree not to travel to a malaria endemic region until 28 days after CHMI.
17. Willing to take anti-malarial medicines if deemed necessary per protocol or at investigator discretion.
18. Passing score on written Assessment of Understanding (minimum passing score of 80 percent required for participation and one repeat testing is allowed if necessary).

1. Unable to provide informed consent including inability to pass the test of understanding.
2. Receipt of a malaria vaccine in a prior clinical trial.
3. History of malaria infection within 2 years prior to study participation.
4. History of a splenectomy or sickle cell disease.
5. History of a non-febrile seizures or complex febrile seizures.
6. Current use of systemic immunosuppressant/immunomodulatory pharmacotherapy.
7. Receipt of a live vaccine within 4 weeks of first vaccination or of 3 or more non-live vaccines within 2 weeks of first vaccination.
8. Receipt of a live vaccine within 4 weeks of CHMI for infectivity controls or of 3 or more non-live vaccines within 2 weeks of CHMI for infectivity controls.
9. Females who are breast-feeding, pregnant or planning to become pregnant during the study period.
10. Known allergy to atovaquone-proguanil (Malarone(R)), artemether-lumefantrine (Coartem(R)), or any component of the investigational products.
11. History of anaphylaxis or other life-threatening reaction to a vaccine.
12. Participation in any study of investigational vaccine/drug \<4 weeks before enrollment that in the estimation of the site PI might adversely affect safety or data quality.
13. Evidence of increased cardiovascular disease risk (defined as \>10 percent five-year risk by non-laboratory method or prior history of myocardial infarction or myocarditis.
14. Plan to participate in another investigational vaccine/drug research during the study.
15. Plan for major surgery between enrollment until 28 days post-CHMI.
16. Current or anticipated use of any drug with anti-malarial activity that would precede or coincide with malaria challenge or vaccination\* \*Such medications include but are not limited to doxycycline, tetracycline, erythromycin, clindamycin, azithromycin, trimethoprim/sulfamethoxazole, atovaquone, proguanil, pyrimethamine, quinine, tafenoquine, primaquine, artemisinin derivatives, chloroquine and other 4-amino and 8-aminoquinolines.
17. Current or anticipated use of medications known to cause drug reactions with atovaquone-proguanil or artemether-lumefantrine (e.g., cimetidine, metoclopramide, antacids, and kaolin).
18. Current or anticipated use of medications associated with moderate or high risk for prolonging the QT interval\*
19. Current or anticipated use of medications that undergo clinically significant metabolism via the cytochrome enzyme CYP2D6.\*
20. Current or anticipated use of medications that undergo clinically significant metabolism via CYP3A4 or are clinically significant inhibitors or strong inducers of CYP3A4.\*,\*\*
21. Current or anticipated use of medications that have a clinically significant mixed effect on CYP3A4 (e.g., ritonavir, efavirenz).
22. Known disturbances of the electrolyte balance (e.g., hypokalemia or hypomagnesemia).
23. Positive human immunodeficiency virus (HIV) or hepatitis B surface antigen (HbsAg) serology, or hepatitis C virus (HCV) seropositivity with evidence of HCV viremia.
24. Positive Plasmodium 18S rRNA Reverse Transcription Polymerase Chain Reaction (RT-PCR) at baseline.
25. An abnormal electrocardiogram\*
26. History or family history of prolongation of the QT interval.
27. Any other exclusionary medical, psychiatric, social, behavioral or occupational condition or situation as judged by the site PI intended to ensure participant safety and quality of the trial\* \*These kind of exclusionary medical, psychiatric, social, behavioral or occupational condition(s) or situation(s) (including active alcohol or drug abuse) include aspects that could impair the participant's ability to give informed consent, increase the risk to the participant of participation in the study, affect the ability of the participant to participate fully in the study, or negatively impact the quality, consistency, integrity or interpretation of data derived from their participation in the study.

Contacts and Locations

Study Locations (Sites)

The University of Washington - Virology Research Clinic

Seattle, Washington, 98104

United States

Collaborators and Investigators

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-07-23

Study Completion Date2027-03-30

Study Record Updates

Study Start Date2025-07-23

Study Completion Date2027-03-30

Terms related to this study

Keywords Provided by Researchers

Artemether/lumefantrine (Coartem(R))
Atovaquone/proguanil (Malarone(R))
CHMI
controlled
First-in-human
Malaria
Plasmodium falciparum
Saline
Sanaria(R) PfSPZ Challenge (7G8)
Sanaria(R) PfSPZ-LARC2
Sentinel
Vaccine

Additional Relevant MeSH Terms

Malaria