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Safety and Protective Efficacy of Pb(PfCS@UIS4) (PbVac)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03138096
Recruitment Status : Completed
First Posted : May 3, 2017
Last Update Posted : November 26, 2018
Sponsor:
Collaborators:
Havenziekenhuis
Erasmus Medical Center
The PATH Malaria Vaccine Initiative (MVI)
Information provided by (Responsible Party):
Radboud University

Brief Summary:
In the underlying study, a genetically modified P. berghei parasite is used. P. berghei is one of the four Plasmodium species that causes malaria in rodents. The hypothesis is that immunization of humans with P. berghei will induce a cross-species immune response without the risk of a breakthrough infection. To further increase the potential for protective efficacy, the P. falciparum circumsporozoite (CS)- protein gene has been integrated in the P. berghei parasite, generating a genetically modified P. berghei parasite, abbreviated as Pb(PfCS@UIS4).

Condition or disease Intervention/treatment Phase
Malaria,Falciparum Plasmodium Falciparum Plasmodium Berghei Controlled Human Malaria Infection (CHMI) Biological: Pb(PfCS@UIS4)-infected mosquitoes Other: Challenge infection P. falciparum Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Safety and Protective Efficacy of Genetically Modified Plasmodium Berghei (Pb(PfCS@UIS4)) Malaria Parasites in Healthy Volunteers
Actual Study Start Date : May 29, 2017
Actual Primary Completion Date : March 28, 2018
Actual Study Completion Date : October 3, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Group 1
(Group 1) will be exposed to bites of five Pb(PfCS@UIS4)-infected mosquitoes
Biological: Pb(PfCS@UIS4)-infected mosquitoes
Pb(PfCS@UIS4)-infected mosquitoes

Experimental: Group 2
(group 2) will be exposed to 25 Pb(PfCS@UIS4)-infected mosquito bites
Biological: Pb(PfCS@UIS4)-infected mosquitoes
Pb(PfCS@UIS4)-infected mosquitoes

Experimental: Group 3
(group 3) will be exposed to 75 Pb(PfCS@UIS4)-infected mosquito bites
Biological: Pb(PfCS@UIS4)-infected mosquitoes
Pb(PfCS@UIS4)-infected mosquitoes

Other: Challenge infection P. falciparum
Challenge infection with bites of five infected Pf mosquitoes

Group 4
Infectivity control group
Other: Challenge infection P. falciparum
Challenge infection with bites of five infected Pf mosquitoes

Group 5
Infectivity control group
Other: Challenge infection P. falciparum
Challenge infection with bites of five infected Pf mosquitoes




Primary Outcome Measures :
  1. Frequency and magnitude of adverse events in study groups [Safety] [ Time Frame: through study completion, up to 8 months ]
    Frequency and magnitude of adverse events in study groups.

  2. Presence of parasitemia after exposure to Pb(PfCS@UIS4) [Safety] [ Time Frame: through study completion, up to 8 months ]
    Presence of parasitemia after exposure to Pb(PfCS@UIS4), as assessed by thick smear.

  3. Time to parasitemia after CHMI with the wild-type NF54 P. falciparum strain [Efficacy] [ Time Frame: through study completion, up to 8 months ]
    Time to parasitemia after CHMI with the wild-type NF54 P. falciparum strain, as detected by qPCR.


Secondary Outcome Measures :
  1. Immunogenicity of Pb(PfCS@UIS4) as assessed by ELISA [ Time Frame: through study completion, up to 8 months ]
    Immunogenicity of Pb(PfCS@UIS4) as assessed by ELISA


Other Outcome Measures:
  1. Cellular immune responses after exposure to Pb [Exploratory endpoint] [ Time Frame: through study completion, up to 8 months ]
    Cellular and humoral immune responses after exposure to Pb(PfCS@UIS4) and challenge with P. falciparum

  2. Humoral immune responses after exposure to Pb [Exploratory endpoint] [ Time Frame: through study completion, up to 8 months ]
    Humoral immune responses after exposure to Pb(PfCS@UIS4)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Subject is aged ≥ 18 and ≤ 35 years and in good health.
  2. Subject has adequate understanding of the procedures of the study and is able and willing (in the investigator's opinion) to comply with all study requirements.
  3. Subject is willing to complete an informed consent questionnaire and is able to answer all questions correctly.
  4. Subject is able to communicate well with the investigator and is available to attend all study visits, lives in Rotterdam or in proximity to the trial centre (can be on site within 1 hour) or is willing to stay in a hotel close to the trial centre during part of the study (phase 1: from day of immunization to day 12 post-immunization; phase 2: from day of immunization to day 8 post-immunization.
  5. The subject will remain within the Netherlands from day -1 until day +28 after immunization during phase 1; from day -1 until day 12 after each immunization during phase 2, and during the challenge period, will not travel to a malaria-endemic area during the study period, and is reachable (24/7) by mobile telephone throughout the entire study period.
  6. Subject agrees to their general practitioner being informed and contacted about their participation in the study and agrees to sign a form to request the release by their General Practitioner (GP), and medical specialist when necessary, to the investigator(s), of any relevant medical information concerning possible contra-indications for participation in the study.
  7. The subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period and for a defined period thereafter according to current Sanquin guidelines (3 years minimum, depending on serology).
  8. For female subjects: subject agrees to use continuous adequate contraception** and not to breastfeed for the duration of study.
  9. Subject agrees to refrain from intensive physical exercise (disproportionate to the subject's usual daily activity or exercise routine) during the malaria challenge period.
  10. Subject agrees to avoid additional triggers that may cause elevations in liver enzymes including alcohol from baseline up to 1 week post treatment.
  11. Subject has signed written informed consent to participate in the trial.

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

  1. Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following.

    1.1. Body weight <50 kg or Body Mass Index (BMI) <18 or >30 kg/m2 at screening. 1.2. A heightened risk of cardiovascular disease, as determined by: an estimated ten year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically significant arrhythmia's, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiac events in 1st or 2nd degree relatives <50 years old.

    1.3. A medical history of functional asplenia, sickle cell trait/disease, thalassaemia trait/disease or G6PD-deficiency.

    1.4. History of epilepsy in the period of five years prior to study onset, even if no longer on medication.

    1.5. Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) 1.6. Chronic use of i) immunosuppressive drugs, ii) antibiotics, iii) or other immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period.

    1.7. Any recent or current systemic therapy with an antibiotic or drug with potential anti-malarial activity (chloroquine, atovaquone-proguanil, arthemether-lumefantrine, sulfadoxine-pyrimethamine, doxycycline, tetracycline, piperaquine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, erythromycin, hydroxychloroquine, etc.) (allowable timeframe for use at the Investigator's discretion).

    1.8. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.

    1.9. Any history of treatment for severe psychiatric disease by a psychiatrist in the past year.

    1.10. History of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset, positive urine toxicology test for cocaine or amphetamines at screening or at inclusion, or positive urine toxicology test for cannabis at inclusion.

  2. For female subjects: positive urine pregnancy test at screening and/or at the baseline visits, including baseline of immunizations (I-1) and or baseline before CHMI (C-1).
  3. Any history of malaria, positive serology for P. falciparum, or previous participation in any malaria (vaccine) study.
  4. Known hypersensitivity to or contra-indications (including co-medication) for use of sulfadoxine-pyrimethamine, piperaquine, chloroquine, Malarone®, artemether-lumefantrine, primaquine or history of severe (allergic) reactions to mosquito bites.
  5. Receipt of any vaccinations in the 3 months prior to the start of the study or plans to receive any other vaccinations during the study period or up to 8 weeks thereafter.
  6. Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
  7. Being an employee or student of the department of Medical Microbiology and Infectious Diseases of the Erasmus MC or Radboudumc, or the department of Internal Medicine of the Radboudumc or Havenziekenhuis.
  8. Any other condition or situation that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03138096


Locations
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Netherlands
Havenziekenhuis
Rotterdam, Netherlands
Sponsors and Collaborators
Radboud University
Havenziekenhuis
Erasmus Medical Center
The PATH Malaria Vaccine Initiative (MVI)
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Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT03138096    
Other Study ID Numbers: PbVac
First Posted: May 3, 2017    Key Record Dates
Last Update Posted: November 26, 2018
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Results will be published

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases