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Clinical Trial for Malaria Vaccines to Test for Safety, Immune Response and Protection Against Malaria (DNA-Ad)

10 février 2021 mis à jour par: U.S. Army Medical Research and Development Command

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

The purpose of this study is to test the safety and effectiveness of a new malaria vaccine, the DNA-Ad vaccine. The study is specifically looking at a vaccine regimen against Plasmodium falciparum, the most deadly form of malaria.

Aperçu de l'étude

Statut

Complété

Les conditions

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

82

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

    • Maryland
      • Silver Spring, Maryland, États-Unis, 20910
        • Clinical Trials Center, WRAIR

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 50 ans (Adulte)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: La prévention
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 1
DNA vaccine prime Given at 0, 4, and 8 weeks
2 mg total dose (1 mg per construct in a volume of 1 mL)
Expérimental: 2
adenovirus type 5 vaccine boost Given at 24 weeks
2 x 1010 particle units (pu) (1 x 1010 pu per each of 2 constructs including CSP and AMA1 respectively)

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Number of adverse events
Délai: 5 years

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.

  1. Occurrence, severity, and duration of any solicited symptoms starting on the day of immunization through day 7 after each immunization
  2. Occurrence of any unsolicited symptoms, abnormal physical findings, and laboratory values starting from the day of immunization through day 28 after each immunization
  3. Occurrence of any serious adverse events, as defined in 21 CFR 312.32, during the five-year study period
5 years

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Number of sterile or partial protections
Délai: 28 days after malaria challenge
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.
28 days after malaria challenge
Number of humoral immunity expressions
Délai: 28 days after malaria challenge
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.
28 days after malaria challenge
Number of cellular immunity expressions
Délai: 28 days after malaria challenge
The DNA-Ad vaccine is considered to confer cellular immunity if a positive ELISpot response is detected after immunization
28 days after malaria challenge

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Les enquêteurs

  • Chercheur principal: Judith Epstein, MD, US Military Vaccine Program, NMRC PI, Naval Officer

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

1 mai 2009

Achèvement primaire (Réel)

1 avril 2014

Achèvement de l'étude (Réel)

1 juillet 2015

Dates d'inscription aux études

Première soumission

27 mars 2009

Première soumission répondant aux critères de contrôle qualité

27 mars 2009

Première publication (Estimation)

30 mars 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

11 février 2021

Dernière mise à jour soumise répondant aux critères de contrôle qualité

10 février 2021

Dernière vérification

1 février 2021

Plus d'information

Termes liés à cette étude

Mots clés

Autres numéros d'identification d'étude

  • WRAIR 1550
  • HRPO #A-15350
  • NMRC.2009.0004

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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