- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT00870987
Clinical Trial for Malaria Vaccines to Test for Safety, Immune Response and Protection Against Malaria (DNA-Ad)
Clinical Trial on Safety, Immunogenicity, and Efficacy of a Prime Boost Regimen of DNA- and Adenovirus-vectored Malaria Vaccines Encoding Plasmodium Falciparum Circumsporozoite Protein and Apical Membrane Antigen 1 in Healthy Malaria-Naïve Adults in the US
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
The goal of this study is to evaluate if the DNA-Ad vaccine that targets both the liver and blood stages of the malaria life cycle is safe and protective, in hopes to develop a vaccine to prevent infection and/or lessen the severity of disease caused by the P. falciparum malaria parasite. More specifically, this DNA-Ad vaccine contains a liver stage antigen (circumsporozoite protein) and an antigen (apical membrane antigen 1) that is present in both the liver and blood stages designed to prevent infection by killing the majority of developing parasites in the liver and to prevent severe disease and death should break-through blood stage infections occur.
This study is an open-label, Phase 1/2a study designed to assess the safety, immunogenicity, and efficacy of a DNA-Ad vaccine in healthy adults who are Ad5 seropositive or seronegative. The vaccinated study group will consist of up to 20 healthy, malaria-naïve adults aged 18 to 50 years, who have been previously screened to meet inclusion and exclusion criteria and will receive three priming doses of the DNA vaccine and a single dose of the boosting component, an adenovirus-vectored vaccine to be given 4 months after the last dose of DNA. Follow up visits will occur after each immunization. The control group will consist of six non-immunized subjects that will participate in a challenge to assure that vaccinated subjects were indeed exposed to P. falciparum. Subjects in both the immunized and control cohorts will receive malaria challenge. Subjects will be assessed for development of parasitemia by daily blood smears and will be closely observed in hotel after the challenge. Subjects will then be followed periodically and have the final in-person visit twelve weeks after the challenge, followed by annual contact by phone, email, or mailings up to five years after the first dose of immunization per FDA recommendation.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
- Fase 1
Contactos e Locais
Locais de estudo
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Maryland
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Silver Spring, Maryland, Estados Unidos, 20910
- Clinical Trials Center, WRAIR
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Healthy adults 18 to 50 years of age (inclusive)
- Women who are not pregnant by a current negative pregnancy test or of non-childbearing potential
- Willing to use an FDA approved birth control method including condoms, birth control pills, sterility surgery, or intrauterine devices among others, from time of enrollment until 6 months after the end of the active phase of the study
- Able to provide free and willing written informed consent to participate
- Score at least 80% correct on a 10 question Assessment of Understanding
- No plans to travel to a malaria endemic area during the course of the study
- Free of significant health problems as established by medical history and clinical examination completed prior to the study
- Available to participate and reachable for duration of study (up to five years)
- Only subjects with no or low cardiac risk factors according to the Gaziano study [53] and a normal EKG will be included in the study
Exclusion Criteria:
- Pregnant (positive HCG) or nursing at screening or plans to become pregnant or nurse from the time of enrollment until 6 months after sporozoite challenge
- Any past history of malaria
- History of receipt of malaria vaccine
- Plans to travel to malarious areas during the study period
- Use of any investigational or non-registered drug or vaccine within 30 days prior to enrollment
- Seropositive for HIV, hepatitis C virus (antibodies to HIV and HCV), and/or HBsAg
- Subjects in the immunized group who engage in high-risk behaviors for acquiring HIV
- Allergy to antimalarials or significant (e.g. systemic) hypersensitivity reactions to mosquito bites (local hypersensitivity reactions at the site of a mosquito bite are not an exclusion criterion)
- History of psoriasis (given its interaction with chloroquine)
- Use or planned use of any drugs with significant anti-malarial activity, such as doxycycline, clindamycin, azithromycin, or trimethoprim/sulfamethoxazole among others during the study period (subjects can withhold the use of these medications during the study period if approved by their primary care physicians, at the minimum starting from four weeks before vaccine administration until four weeks after becoming parasitemic) Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection and history of splenectomy
- Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of challenge
- A family history of congenital or hereditary immunodeficiency
- Chronic or active neurologic disease including seizure disorder
- Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by medical history, physical examination, or abnormal baseline laboratory screening tests.
- Abnormal baseline EKG obtained at screening
- Acute disease at the time of enrollment
- Hepatomegaly, right upper quadrant abdominal pain or tenderness: noted by physical exam during the screening process.
- Administration of immunoglobulins and/or any blood products within the three months preceding immunization during the study period
- Use of kanamycin or related antibiotics
- Suspected or known current alcohol abuse/drug abuse as obtained by history and physical examination
- Inability to make follow-up visits
- Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Prevenção
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: 1
DNA vaccine prime Given at 0, 4, and 8 weeks
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2 mg total dose (1 mg per construct in a volume of 1 mL)
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Experimental: 2
adenovirus type 5 vaccine boost Given at 24 weeks
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2 x 1010 particle units (pu) (1 x 1010 pu per each of 2 constructs including CSP and AMA1 respectively)
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Number of adverse events
Prazo: 5 years
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The vaccine will be considered safe and well-tolerated if there are no severe or serious adverse events (AE) related to vaccine administration or if any severe events are relatively benign (e.g. erythema meeting criteria for severe due to its dimensions but not significantly affecting the activities of daily living for the subject) or brief in duration (e.g. less than 48 hours). The AEs will be assessed according to the method below.
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5 years
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Number of sterile or partial protections
Prazo: 28 days after malaria challenge
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The DNA-Ad vaccine is considered efficacious if it offers any degree of sterile or partial protection that reaches statistical significance (p<0.05).
The vaccine efficacy will be determined by two parameters: 1) sterile protection for 28 days after challenge, 2) partial protection as determined by delay to parasitemia by smears and PCR.
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28 days after malaria challenge
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Number of humoral immunity expressions
Prazo: 28 days after malaria challenge
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The DNA-Ad vaccine is considered to confer humoral immunity if the increase of antibody response for CSP or AMA1 by ELISA post immunization is statistically significant (p<0.05)
compared to the levels before immunization.
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28 days after malaria challenge
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Number of cellular immunity expressions
Prazo: 28 days after malaria challenge
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The DNA-Ad vaccine is considered to confer cellular immunity if a positive ELISpot response is detected after immunization
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28 days after malaria challenge
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Judith Epstein, MD, US Military Vaccine Program, NMRC PI, Naval Officer
Publicações e links úteis
Publicações Gerais
- Sedegah M, Peters B, Hollingdale MR, Ganeshan HD, Huang J, Farooq F, Belmonte MN, Belmonte AD, Limbach KJ, Diggs C, Soisson L, Chuang I, Villasante ED. Vaccine Strain-Specificity of Protective HLA-Restricted Class 1 P. falciparum Epitopes. PLoS One. 2016 Oct 3;11(10):e0163026. doi: 10.1371/journal.pone.0163026. eCollection 2016. Erratum In: PLoS One. 2016 Dec 20;11(12 ):e0168952.
- Aguiar JC, Bolton J, Wanga J, Sacci JB, Iriko H, Mazeika JK, Han ET, Limbach K, Patterson NB, Sedegah M, Cruz AM, Tsuboi T, Hoffman SL, Carucci D, Hollingdale MR, Villasante ED, Richie TL. Discovery of Novel Plasmodium falciparum Pre-Erythrocytic Antigens for Vaccine Development. PLoS One. 2015 Aug 20;10(8):e0136109. doi: 10.1371/journal.pone.0136109. eCollection 2015.
- Sedegah M, Hollingdale MR, Farooq F, Ganeshan H, Belmonte M, Huang J, Abot E, Limbach K, Chuang I, Tamminga C, Epstein JE, Villasante E. Controlled Human Malaria Infection (CHMI) differentially affects cell-mediated and antibody responses to CSP and AMA1 induced by adenovirus vaccines with and without DNA-priming. Hum Vaccin Immunother. 2015;11(11):2705-15. doi: 10.1080/21645515.2015.1019186. Epub 2015 Aug 20.
- Sedegah M, Hollingdale MR, Farooq F, Ganeshan H, Belmonte M, Kim Y, Peters B, Sette A, Huang J, McGrath S, Abot E, Limbach K, Shi M, Soisson L, Diggs C, Chuang I, Tamminga C, Epstein JE, Villasante E, Richie TL. Sterile immunity to malaria after DNA prime/adenovirus boost immunization is associated with effector memory CD8+T cells targeting AMA1 class I epitopes. PLoS One. 2014 Sep 11;9(9):e106241. doi: 10.1371/journal.pone.0106241. eCollection 2014.
- Tamminga C, Sedegah M, Maiolatesi S, Fedders C, Reyes S, Reyes A, Vasquez C, Alcorta Y, Chuang I, Spring M, Kavanaugh M, Ganeshan H, Huang J, Belmonte M, Abot E, Belmonte A, Banania J, Farooq F, Murphy J, Komisar J, Richie NO, Bennett J, Limbach K, Patterson NB, Bruder JT, Shi M, Miller E, Dutta S, Diggs C, Soisson LA, Hollingdale MR, Epstein JE, Richie TL. Human adenovirus 5-vectored Plasmodium falciparum NMRC-M3V-Ad-PfCA vaccine encoding CSP and AMA1 is safe, well-tolerated and immunogenic but does not protect against controlled human malaria infection. Hum Vaccin Immunother. 2013 Oct;9(10):2165-77. doi: 10.4161/hv.24941. Epub 2013 Jun 4.
- Chuang I, Sedegah M, Cicatelli S, Spring M, Polhemus M, Tamminga C, Patterson N, Guerrero M, Bennett JW, McGrath S, Ganeshan H, Belmonte M, Farooq F, Abot E, Banania JG, Huang J, Newcomer R, Rein L, Litilit D, Richie NO, Wood C, Murphy J, Sauerwein R, Hermsen CC, McCoy AJ, Kamau E, Cummings J, Komisar J, Sutamihardja A, Shi M, Epstein JE, Maiolatesi S, Tosh D, Limbach K, Angov E, Bergmann-Leitner E, Bruder JT, Doolan DL, King CR, Carucci D, Dutta S, Soisson L, Diggs C, Hollingdale MR, Ockenhouse CF, Richie TL. DNA prime/Adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity. PLoS One. 2013;8(2):e55571. doi: 10.1371/journal.pone.0055571. Epub 2013 Feb 14.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- WRAIR 1550
- HRPO #A-15350
- NMRC.2009.0004
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