15 Clinical Trials for Various Conditions
This clinical study is a phase 4, single-site, open-label pharmacokinetic (PK) study of IV artesunate in up to 100 Ugandan children 6 months-14 years of age who are diagnosed with severe malaria according to standardized World Health Organization (WHO) criteria (any P. falciparum parasitemia and the presence of danger signs). Participants will receive the standard of care IV artesunate for initial treatment of severe malaria per WHO guidelines: children weighing \<20 kg should receive 3.0 mg/kg/dose compared to children weighing =20 kg who should receive 2.4 mg/kg/dose, at times 0, 12, 24, 48 and 72 hours (WHO 2015). Parenteral treatment will be administered for a minimum of 24 hours (irrespective of the patient's ability to tolerate oral medication earlier), after which patients will be evaluated clinically and assessed for ability for oral intake of antimalarials. Children who are able to transition to oral antimalarial therapy will initiate a 3-day course of artemisinin-combination oral therapy per national guidelines. The primary objective of the study is to determine the relationship between DHA exposures following IV artesunate dosing and markers of physiologic dysfunction associated with severe malaria in Ugandan children.
This is a study to evaluate the safety, immunogenicity, and efficacy of a recombinant circumsporozoite protein (rCSP) malaria vaccine administered with and without AP 10-602 \[Glucopyranosyl Lipid A (GLA) in liposome Quillaja saponaria 21 formulation (LSQ)\] adjuvant. 59 healthy adult, malaria naive volunteers aged 18 to 45 will receive vaccination with or without adjuvant (10 of those volunteers will receive rCSP alone) in five dose escalating groups. Each group will receive 3 vaccination doses total, with intramuscular (IM) injections on days 1, 29, and 85. A sixth group of 6 volunteers will receive no vaccinations and will participate as a control in a Controlled Human Malaria Infection (CHMI) challenge with two of the vaccinated groups. The study will be conducted at the Center for Vaccine Development (CVD) in Baltimore, Maryland. The patient participation duration is expected to be up to 886 days (up to 117 days for nonvaccination group). This study will test two hypotheses: (1) the rCSP/AP 10-602 \[GLA-LSQ\] candidate malaria vaccine will induce an immune response in a dose-dependent manner as measured by anti-CSP antibody titer via ELISA and (2) the rCSP/AP 10-602 \[GLA-LSQ\] candidate malaria vaccine will provide a minimum of 50% efficacy in vaccines compared to unvaccinated infectivity controls. The primary objective is to assess the safety and reactogenicity of candidate rCSP/AP 10-602 \[GLA-LSQ\] malaria vaccine when administered intramuscularly on a 1, 29, and 85 day schedule (Groups 1-3, 4B, 5) and on a 1 and 490 day schedule (Group 4) to healthy malaria-naive adults aged 18-45 years.
This Phase 1 trial will include 16 subjects who will receive the Genetically-attenuated p52-/p36-/sap1- Plasmodium falciparum Parasites (GAP3KO) vaccine administered by the bite of approximately 200 infected Anopheles stephensi Mosquitoes in a controlled clinical environment and 12 Controlled Human Malaria Infection (CHMI) infectivity controls (six for each of the two CHMIs). Subjects will be observed for adverse events after each GAP3KO administration. Solicited local and systemic Adverse Events (AEs) will be recorded on a memory aid beginning of the day of first vaccine administration and continuing through 28 days after the last administration. During the vaccination phase clinical laboratory evaluations for safety will be performed on venous blood. Unsolicited AEs will be collected from the day of first vaccination through 28 days after last vaccination and serious adverse events (SAEs) will be collected from the day of first GAP3KO administration through the end of study follow-up. Subjects will be monitored for possible breakthrough peripheral parasitemia with qRT-PCR testing. Four weeks after the last GAP3KO administration, all subjects who completed the immunization phase (up to 16) and a group of six malaria-naïve infectivity controls will be challenged on the same day with wild-type Plasmodium falciparum NF54 sporozoites. Approximately twenty-six weeks after that challenge, all of the protected subjects in Arms 1 and 2 (up to 16) and another six malaria-naïve infectivity controls will receive five infectious A. stephensi mosquito bites on the same day using standard CHMI procedures. For subjects in Study Arms 1 and 2 without documented parasitemia additional post-CHMI follow-ups will occur. For subjects in Study Arms 1 and 2 with documented parasitemia after the first CHMI or who are discontinued for other reasons after the first CHMI, and for the infectivity controls, additional follow ups will occur. Serious Adverse Events (SAEs) will be recorded from the day of CHMI through the end of study follow up and clinical laboratory evaluations for safety will be performed on Day 29 and as clinically indicated (all subjects) and, for subjects with documented parasitemia, on the day malaria treatment is initiated and three days after malaria treatment is initiated. The primary objectives are: 1) To assess the safety and reactogenicity of candidate GAP3KO malaria vaccine when administered by the bite of approximately 200 infected mosquitoes on a five dose schedule, with the first four vaccinations given four weeks apart and the fifth vaccination given eight weeks after the fourth vaccination, and on a three dose schedule, with the second vaccination given four weeks after the first vaccination and the third vaccination given eight weeks after the second vaccination, to healthy malaria-naïve adults aged 18 through 50 years , 2) To confirm attenuation of GAP3KO parasites by assessing the occurrence of breakthrough peripheral parasitemia from the time of first GAP3KO administration through 28 days after last GAP3KO administration.
This is a phase I study that will assess the acquisition of immunity to Pf malaria over the course of 5 sequential Controlled Human Malaria Infections (CHMI) over 2-4 years, in 10 healthy adult participants. 10 subjects will initially be challenged with 5 uninfected mosquitoes (mock), followed by 5 challenges with 5 mosquitoes infected with drug sensitive, P. falciparum parasites (strain NF54) 2, 8, 14-20, 20-32, and 32-36 months later. For the final four infective CMHIs six additional immunologic malaria-naïve subjects will be enrolled and challenged as infectivity controls. If dropouts occur within the original 10 person cohort, and two or more CHMI remain, back-up replacement volunteers will be recruited to undergo successive CHMI with the core group. All volunteers (repeat CHMI subjects and infectivity controls) will be evaluated as part of an inpatient stay (or outpatient daily follow-up) to diagnose Pf malaria infection and treat with Coartem(R) (artemether/lumefantrine) or Malarone(R) (Atovaquone/proguanil). Daily observation will occur from Study Days 9-19 or until three-day directly observed therapy for P. falciparum infection is complete and two negative smears separated by a time interval \>12 hours have been documented. A third negative smear \>12 hours after the previous two daily smears will be documented to affirm malaria cure. Infectivity Controls enrolled as part of CHMI #5 will be treated based on concomitant us qPCR results. The repeat CHMI subjects will have additional outpatient visits days 1, 3, 5, and 7 after the challenge to obtain blood samples to monitor the development of immunity. The study is expected to last for 48 months and will include approximately 34 healthy male and female volunteers (10 active study volunteers and 18 naïve controls to confirm Pf infectivity during the 2nd -5th CHMI challenges) ages 18 to 50 years, inclusive, from the greater Baltimore community. The primary objective of this study is to determine whether protective immunity against parasite infection develops following repeat CHMI.
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.
This phase I trial of the replication-intact PfSPZ Challenge vaccine given under CQ cover will enroll 28 healthy volunteers to receive PfSPZ or placebo, as well as suppressive doses of chloroquine (CQ)on varying schedules. 10 weeks post 3rd immunization subjects will be subjected to controlled human malarial infection. The primary objective of this study is to evaluate the safety and tolerability of escalating doses of Sanaria PfSPZ Challenge administered by DVI on varying schedules to healthy malaria-naïve adults taking suppressive doses of CQ (PfSPZ-CVac).
The purpose of this study is to determine how many infected mosquito bites are required to reliably give volunteers a case of malaria. It is expected that volunteers will develop malaria and may have symptoms. Safety is the main concern. A malaria challenge is given by allowing a volunteer to receive 1, 3, or 5 mosquito's bites. Then participants are carefully followed and blood is tested. The study will also look at how immune systems (the cells and substances that protect the body from infection and foreign matter) respond after mosquito bite challenges. About 38 subjects (aged 18-40 years) from the greater Baltimore, Maryland (United States) community will participate and may stay overnight for 10 days at a local medical center. Procedures include medical screening, assignment to a dose group, a mosquito bite challenge, and 56 day follow-up. Volunteers will be contacted by telephone at 6 and 12 months after the malaria challenge.
Malaria is caused by a parasite carried by a mosquito. Currently, there is no vaccine licensed to prevent malaria. The purpose of this study is to find the most effective and safest dose of an experimental vaccine for the treatment of malaria. Participants will include 72 healthy adults, ages18 to 45, enrolled at Vanderbilt University Medical Center and Stanford University. Volunteers will receive 3 doses of either the malaria vaccine or placebo (contains no vaccine) by injection into a muscle at 0, 1 and 6 months. Investigators will evaluate how the body responds to increasing dosage strengths of the vaccine. Study procedures include physical exam, multiple blood draws, and completion of a memory aid (diary). Each participant will be actively involved in the study for about 12 months. Then, an annual phone call will be made to check for any serious illness events for a period of 5 years.
The study is a single centre, randomised, placebo-controlled, double-blind study with DSM265 including up to two cohorts of healthy male and female volunteers aged 18 to 45 years. The study will be conducted into two sequential parts (Cohort 1 and Cohorts 2a and 2b).
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).
The proposed study is a Phase 1 study with controlled human malaria infection (CHMI) designed primarily to evaluate the safety of the FMP012 combined with AS01B adjuvant system. AS01B is a proprietary current good manufacturing practices (cGMP) grade adjuvant manufactured by GlaxoSmithKline (GSK) Biologicals. It is a formulation based on liposomes mixed with the immunostimulants monophosphoryl lipid (MPL) and Quillaja saponaria (QS)-21. The immunogenicity and efficacy of this new candidate vaccine will be evaluated in addition to safety.
Clinical pneumonia is a leading cause of pediatric hospitalization. The etiology is generally bacterial or viral. Prompt and optimal treatment of pneumonia is critical to reduce mortality. However, adequate pneumonia management is hampered by: a) the lack of a diagnostic tool that can be used at point-of-care (POC) and promptly and accurately allow the diagnosis of bacterial disease and b) lack of a prognostic POC test to help triage children in need of intensive assistance. Antibiotic therapy is frequently overprescribed as a result of suspected bacterial infections resulting in development of antibiotic resistance. Conversely, in malaria-endemic areas, antibiotics may also be "underprescribed" and children with bacterial pneumonia sent home without antibiotic therapy, when the clinical pneumonia is mistakenly attributed to a co-existing malaria infection. The investigators previously identified combinations of protein with 96% sensitivity and 86% specificity for detecting bacterial disease in Mozambican children with clinical pneumonia. The investigators' prior work showed that it is possible to identify biosignatures for diagnosis and prognosis using few proteins. Recently, other authors also identified different accurate biosignatures (e.g., IP-10, TRAIL and CRP). In this study, the investigators propose to validate and improve upon previous biosignatures by testing prior combinations and seeking novel combinations of markers in 900 pediatric inpatients aged 2 months to 5 years with clinical pneumonia in The Gambia. The investigators will also use alternative case criteria and seek diagnostic and prognostic combination of markers. This study will be conducted in Basse, rural Gambia, in two hospitals associated with the Medical Research Council Unity The Gambia (MRCG). Approximately 900 pediatric patients with clinical pneumonia aged 2 months to 5 years of age will be enrolled. Patients will undergo standard of care test and will have blood proteins measured through Luminex®-based immunoassays. Results of this study may ultimately support future development of an accurate point-of-care test for bacterial disease to guide clinicians in choices of treatment and to assist in the prioritization of intensive care in resource-limited settings.
This is a randomized, double blind, placebo-controlled, single site, trial of a condensed regimen of 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) conducted at varying time intervals after the third immunization (14, 42 or 70 days). The trial is designed to simulate pre-deployment immunization of military personnel. Prior studies with this regimen show high level protection (\>80%) against CHMI at 21 days, but the onset and duration of protection have not been fully defined.
This is an open-label evaluation of the safety, tolerability, immunogenicity and efficacy of PfSPZ Vaccine administered by direct venous inoculation (DVI) in healthy, malaria-naïve adult subjects.
The purpose of this study is to identify and screen potential subjects for preliminary eligibility to participate in a malaria related clinical trial conducted at the Seattle Malaria Clinical Trials Center (Seattle MCTC) or one of our partnering sites.