A Phase 1 Trial to Evaluate the Safety and Infectivity of Direct Venous Inoculation of Aseptic, Purified, Cryopreserved Plasmodium Falciparum (7G8 and NF54) Sporozoites in Non-immune Adults in Baltimore, USA
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Plasmodium Falciparum Infection
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- The number and severity of local and systemic solicited and unsolicited reactogenicity symptoms related to PfSPZ Challenge for 7 days following DVI administration
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
This is a single center, randomized and controlled human study to optimize controlled human malaria infection (CHMI) administered by direct venous inoculation (DVI). 36 healthy adults aged between 18 and 45 years, will be randomized to one of five groups and will be inoculated with PfSPZ Challenge DVI. Participation duration is estimated to be 2 months, while the study duration is planned to be 4 months. The primary objective of this study is to assess the safety and reactogenicity of PfSPZ Challenge administered by DVI using 7G8 and NF54 P. falciparum strains.
Detailed Description
The proposed study is a single center, randomized and controlled human study to optimize controlled human malaria infection (CHMI) administered by direct venous inoculation (DVI). 30 to 36 participants will be randomized to one of five groups and will be inoculated with PfSPZ Challenge DVI. All participants recruited will be healthy adults aged between 18 and 45 years. The study duration is 4 months, participation duration is estimated to be 2 months. Safety and infectivity data will be collected for each study product and dose-level. Sera will be collected at baseline and at study day 29 for antibody assays. Participants, and clinical and laboratory investigators will be blinded to group allocation. The study primary endpoint will be reached at study day 29, at which time an interim study report will be generated. The investigators, the sponsor, the data and statistical analysis team, and Sanaria staff will meet in person or by teleconference on day 43 to review infection, pre-patent period, and adverse event results. These results will be made available to members of the International PfSPZ Consortium (I-PfSPZ-C) and if required, to regulatory authorities, including the FDA, to facilitate other PfSPZ Challenge CHMI studies with the appropriate disclaimers. Participants will be followed as outpatients for malaria diagnosis, treatment and follow-up to study day 57. Malaria positivity will be determined by qPCR diagnostics with microscopy as a backup. Participants who test positive for malaria and those who remain negative at study day 29 will be treated with oral atovaquone-proguanil. The primary objective of this study is to assess the safety and reactogenicity of PfSPZ Challenge administered by DVI using 7G8 and NF54 P. falciparum strains. Secondary objectives are to 1) assess the infectivity of four escalating doses of direct venous inoculation (DVI) of the 7G8 clone in comparison with an established dose (100% infective) DVI of the NF54 strain and 2) assess the time to malaria patency for escalating doses of the 7G8 clone compared to a single dose of the NF54 strain.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy adults between the ages of 18 and 45 years, inclusive
- •Able and willing to participate for the duration of the study
- •Able and willing to provide written (not proxy) informed consent
- •Provides informed consent and correctly answers greater than or equal to 70% on the post consent quiz before any study procedures, and is available for all study visits -Note: Two attempts permitted
- •Females of childbearing potential must agree to practice highly effective contraception -Note: Contraception must be practiced from 30 days before the time of enrollment until at least 30 days following inoculation (such as double barrier methods (condoms plus foam or spermicide, diaphragm plus foam or spermicide), licensed intrauterine devices (IUDs), intravaginal or intra/transdermal or oral hormonal methods initiated at least 30 days before inoculation or challenge, documented surgical sterilization via tubal ligation the essure procedure or hysterectomy, abstinence or a vasectomized partner). The contraceptive method should remain unchanged throughout the required period
- •Is in good health, as determined by vital signs (heart rate, blood pressure, oral temperature); medical history; normal laboratory ranges listed in Appendix C; and a physical examination -Note: hemoglobin, white blood cell count, platelet count, glucose (random), serum alanine aminotransferase (ALT), serum creatinine, urine protein and urine blood
- •Agree not to travel to a malaria endemic region during study days 1-29
- •Willing to avoid non-study related blood donation from screening until 3 years (45) following P. falciparum challenge
- •Able to understand and comply with planned study procedures including daily outpatient follow-up visits beginning 5 days after inoculation
Exclusion Criteria
- •Any history of malaria infection, or travel to a malaria endemic region within 3 months before planned date of CHMI
- •History of long-term residence (\>5 years) in an area known to have significant transmission of P. falciparum
- •Positive serology for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B surface antigen (HBsAg)
- •Positive sickle cell screening test or known hemoglobinopathy
- •Current or recent (within the last four weeks) treatment with parenteral or oral corticosteroids (intranasal or inhaled steroids are acceptable), or other immunosuppressive agents, or chemotherapy
- •Screening laboratory values outside protocol-specified acceptable normal ranges as noted in Appendix C, except hematuria\>1+ detected during menses for females. Note: For females who are menstruating, urinalysis frequently tests positive for blood and is not an indicator of poor health status or increased risk; other exceptions include ALT and creatinine below the lower limit of the reference range
- •Known hypersensitivity to components of PfSPZ Challenge, atovaquone-proguanil or artemether-lumefantrine
- •History of acute or chronic medical conditions including, but not limited to, disorders of the liver, kidney, lung, heart, nervous system, or other metabolic or autoimmune/inflammatory conditions
- •History of anaphylaxis or severe hypersensitivity reaction
- •Receipt of an investigational product on study days -31 to -1 or planned receipt of an investigational product on study days 1-
Outcomes
Primary Outcomes
The number and severity of local and systemic solicited and unsolicited reactogenicity symptoms related to PfSPZ Challenge for 7 days following DVI administration
Time Frame: Days 1-7
The number of serious adverse events recorded from study
Time Frame: Days 1-57
Secondary Outcomes
- Percent infectivity of each PfSPZ dose regimen(Days 1-57)
- Time to P. falciparum asexual parasitemia following experimental malaria challenge(Days 1-57)