Clinical Trial of the PfSPZ Vaccine
The purpose of this study is to determine the safety and tolerability of a non-replicating, metabolically active Plasmodium falciparum sporozoite (PfSPZ) vaccine in malaria-naïve healthy volunteers following multiple-dose subcutaneous (SC) or intradermal (ID) administration.
In addition, the investigators wish to evaluate PfSPZ vaccine-mediated protection against P. falciparum challenge in the following 4 groups (see below) and compare protective efficacy of the PfSPZ vaccine when given by SC v ID administration in all these groups:
- Group 1: 4 doses of 7,500 PfSPZ/immunization,
- Group 2: 4 doses of 30,000 PfSPZ/immunization,
- Group 3: 4 doses of 135,000 PfSPZ/immunization
- Group 4: 4 or 6 doses of 135,000 PfSPZ/immunization.
If > 80% protective efficacy is not achieved in Groups 1, 2, or 3, volunteers in Group 4 will receive a fifth and sixth dose.
The first clinical trial of the Pf SPZ vaccine is a Phase 1/2a trial in non-immune healthy adult volunteers. Sanaria is the Sponsor and PATH MVI is funding the trial. The study will be conducted as a collaborative effort between Sanaria, PATH MVI, the NMRC Malaria Program (U.S. Military Malaria Vaccine Program), and the Center for Vaccine Development at the University of Maryland at Baltimore (CVD-UMB). The study will take place at the NMRC Malaria Program Clinical Trials Center on the campus of the National Naval Medical Center in Bethesda, MD and at the CVD and/or General Clinical Research Center, UMB. The study is designed to evaluate the safety, tolerability, immunogenicity and protective efficacy of successively higher doses of the vaccine administered by the subcutaneous (SC) or intradermal (ID) route.
There will be 4 groups of volunteers with each group comprised of a subset of volunteers who receive the vaccine by the SC route and a subset who receive the vaccine by the ID route.
Groups 1-3: The first 3 groups will receive 3 ascending doses of vaccine administered as 4 SC or ID injections separated by 4 week intervals (7,500 PfSPZ/dose, 30,000 PfSPZ/dose, and 135,000 PfSPZ/dose respectively). Each of these groups will be challenged a minimum of 3 weeks after the final dose by exposure to A. stephensi mosquitoes infected with P. falciparum sporozoites. All 3 groups will be followed for safety until 48 weeks after the first immunization.
Group 4: Group 4 will start a minimum of 3 weeks after the first immunization of Group 3. If there is > 80% efficacy in one or more of the subsets of Groups 1, 2, or 3 (SC or ID), Group 4 volunteers will receive 4 immunizations (just like Group 3) but will not have experimental challenge; they will simply be followed for safety for 12 months after the first immunization. The FDA has requested that we follow a group of volunteers receiving the highest dose (135 PfSPZ/immunization) without challenge at 3 weeks. However, if there is NOT > 80% efficacy in one of more subsets of Groups 1, 2, or 3, after a 6 month observation period, Group 4 volunteers will receive two additional monthly immunizations (Immunizations #5 and #6) followed by challenge at approximately 3 weeks after the sixth immunization. All volunteers in Group 4 will be followed for safety until 52 weeks after the first immunization.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Plasmodium falciparum Sporozoite (strain NF-54; Anopheles stephensi mosquitoes) Vaccine, Live, Inactivated (gamma irradiation)
The Center for Vaccine Development, University of Maryland (CVD/UMB)
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT01001650
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
A protozoan parasite of rodents transmitted by the mosquito Anopheles stephensi.
A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.
A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are PLASMODIUM FALCIPARUM; PLASMODIUM MALARIAE; PLASMODIUM OVALE, and PLASMODIUM VIVAX. Species causing infection in vertebrates other than man include: PLASMODIUM BERGHEI; PLASMODIUM CHABAUDI; P. vinckei, and PLASMODIUM YOELII in rodents; P. brasilianum, PLASMODIUM CYNOMOLGI; and PLASMODIUM KNOWLESI in monkeys; and PLASMODIUM GALLINACEUM in chickens.
A surface protein found on Plasmodium species which induces a T-cell response. The antigen is polymorphic, sharing amino acid sequence homology among PLASMODIUM FALCIPARUM; PLASMODIUM CHABAUDI; PLASMODIUM VIVAX; and PLASMODIUM YOELII.
A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics.
To evaluate the prophylactic activity of orally administered DB289 against Plasmodium falciparum in non-immune healthy volunteers who are challenged by the bite of five P. falciparum-infec...
Plasmodium falciparum isolates display a wide genetic diversity with possibly different properties to induce immune responses. These properties could directly influence the ability to indu...
Malaria is responsible for over 2 million deaths each year. The development of an efficient vaccine would present by far the best solution for solving this disastrous situation. Liver-Stag...
Phase I/IIa double-blind randomized (adjuvant)-controlled trial. 16 volunteers are randomized to receive two doses of either 30 µg of PfCS102 formulated in Montanide ISA 720 (verum) or I...
The purpose of this study is to demonstrate that volunteers can be safely and reproducibly infected with Plasmodium vivax (P. vivax) by the bites of experimentally infected Anopheles dirus...
The prodigious rate at which malaria parasites proliferate during asexual blood stage replication, midgut sporozoite production, and intra-hepatic development creates a substantial requirement for ess...
Malaria, which is the result of Plasmodium falciparum infection, is a global health threat that resulted in 655,000 deaths and 216 million clinical cases in 2010 alone. Recent phase 3 trials with mala...
The development of Plasmodium falciparum within the Anopheles gambiae mosquito relies on complex vector-parasite interactions, however the resident midgut microbiota also plays an important role in me...
Dynamics of malaria transmission and susceptibility to clinical malaria episodes following treatment of Plasmodium falciparum asymptomatic carriers: results of a cluster-randomized study of community-wide screening and treatment.
In malaria-endemic countries, large proportions of individuals infected with Plasmodium falciparum are asymptomatic and constitute a reservoir of parasites for infection of newly hatched mosquitoes.
Evidence from clinical trials of malaria vaccine candidates suggests that both cell-mediated and humoral immunity to pre-erythrocytic parasite stages can provide protection against infection. Novel pr...