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Controlled Human Malaria Infection by Intradermal Injection of Plasmodium Falciparum Sporozoites in Tanzanian Adults

Primary Purpose

Malaria

Status
Completed
Phase
Phase 1
Locations
Tanzania
Study Type
Interventional
Intervention
PfSPZ Challenge
Saline
Sponsored by
Sanaria Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Malaria focused on measuring Malaria Challenge, Plasmodium falciparum, PfSPZ Challenge, Controlled, human, malaria infection

Eligibility Criteria

20 Years - 35 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy Male aged between 20-35 years, healthy volunteers
  • Good Health status based on history & clinical examination
  • Residing in or near DaresSalaam
  • Willing to contribute to science in Tanzania
  • Free from malaria parasite by blood smear & qRT-PCR
  • Not suffering from any chronic illness including HIV/AIDS
  • No documented history of malaria infection for the past 5 yrs
  • Able & willing to come for complete one year follow up including minimum of three weeks of hospitalization
  • All volunteers must sign the informed consent form & answer correctly 15 out 15 questions demonstrating their understanding of the meaning & procedures of the study
  • Volunteer agrees to inform study doctor & agrees to release medical information concerning contra-indications for participation in the study
  • Living with a third party that will contact the study team if in case of alteration of consciousness during the first month of the study
  • Willing to undergo a Pf sporozoite challenge.
  • Willing to take curative treatment for malaria (Coartem®) & any other medication which may be prescribed by a study doctor during study period
  • All volunteers agree to stay in the hospital during parts of the study (overnight after challenge, up to 15 days during follow up & 3 days of Coartem® treatment)
  • Reachable (24/7) by mobile phone during the whole study period
  • Agreement not to participate in another study during the study period.
  • Agreement not to donate blood during the study period.
  • Available to attend all study visits
  • Willingness to undergo HIV, hepatitis B & hepatitis C tests

Exclusion Criteria:

  • History of malaria in the past 5 yrs
  • Plans to travel outside the Dar-es-salaam or Coast Region in first month (day 0-28) of the study
  • Plans to travel to highly malarious areas in the 6 months following the study period
  • Previous participation in malaria vaccine study &/or positive serology for Plasmodium falciparum asexual crude extract antibodies above acceptable cut off established for the site.
  • History of arrhythmias or prolonged QT-interval or other cardiac disease
  • Positive family history of in the 1st & 2nd degree relative for cardiac disease <50 yrs old.
  • Volunteers unable to read & write in English & give written informed consent
  • Previous history of drug or alcohol abuse interfering with normal social function
  • A history of psychiatric disease
  • The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (inhaled & topical corticosteroids are allowed) & during the study period
  • A history or confirmed sickle cell anemia, sickle cell trait, thalassemia , thalassemia trait or G6PD deficiency
  • Co-worker of the Ifakara Health Institute
  • Symptoms, physical signs & laboratory values suggestive of systemic disorders including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, & other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers
  • History of diabetes mellitus or cancer
  • An estimated, ten year risk of fatal cardiovascular disease of <5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system
  • Clinically significant abnormalities in electrocardiogram at screening
  • Body Mass Index below 18 or above 30kg/m2
  • Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis or electrolytes
  • Positive HIV, Hepatitis B virus or Hepatitis C Virus tests
  • Participation in any other clinical study within 30 days prior to the onset of the study or during the study period
  • Volunteers unable to be closely followed for social, geographic or psychological reasons
  • Known hypersensitivity of other contra-indications to Coaterm® or Malarone® including treatment taken by the volunteer that interferes with Coartem® or Malarone®
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia

Sites / Locations

  • Bagamoyo Research and Training Center, Ifakara Health Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Group 1 10,000 PfSPZ

Group 2 25,000 PfSPZ

Controls - saline

Arm Description

12 volunteers, ID PfSPZ Challenge total dose 10,000 PfSPZ administered by 2 injections of 50µL each.

12 volunteers, ID PfSPZ Challenge total dose 25,000 PfSPZ administered in 4 injections of 10µL each.

4 Volunteers, ID saline administered in 2 injections of 50µL each and 2 volunteers, ID saline administered in 4 injections of 10µL each.

Outcomes

Primary Outcome Measures

Number of volunteers positive in each group through day 28 of follow up.
Thick smears will be performed according to a standard operating procedure. In short, 15 μL of whole blood will be distributed on standardized 3-well slides, providing an equal slide thickness for all smears. Slides are dried and stained with Giemsa. 200 fields per slide will be read at 1000X. Slides are considered positive if they contain 2 or more parasites per 200 fields.

Secondary Outcome Measures

Time from inoculation until first positive parasitemia by thick smear in each volunteer in the two groups.
Time from inoculation to until first positive parasitemia by qRT-PCR in each volunteer in the two groups.
qRT-PCR will be performed according to standard procedure described in Hermsen et al. Mol. Biochem. Parasitol. 2001; 118: 247-251. In short, qRT-PCR will be performed on the multicopy 18S ribosomal RNA gene. Cultured P. falciparum ring stage parasites are taken as a positive control. All samples are spiked with murine white blood cells, and a murine albumin gene PCR is used to determine efficacy of DNA isolation.
Kinetics of parasitemia in positive volunteers in the two groups as measured by qRT-PCR.
Thick smear, malaria rapid diagnostic test and qRT-PCR samples will be taken from the same 3 mL EDTA vacutainer tube. Histidine Rich Protein 2 based malaria rapid diagnostic tests will be used in parallel to thick smears.
Occurrence or intensity of signs or symptoms in the two groups of volunteers
Signs and symptoms will be recorded at all visits and whenever a trial volunteer reports signs or symptoms to the trial physician between visits. The following signs and symptoms will be solicited: fever, headache, malaise, fatigue, myalgia, arthralgia, nausea, vomiting, chills, diarrhea, abdominal pain (Verhage, Telgt, Bousema, Hermsen, van Gemert, van der Meer, & Sauerwein 2005), chest pain, palpitations and shortness of breath.

Full Information

First Posted
February 23, 2012
Last Updated
September 9, 2014
Sponsor
Sanaria Inc.
Collaborators
Ifakara Health Research and Development Centre, Swiss Tropical & Public Health Institute
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1. Study Identification

Unique Protocol Identification Number
NCT01540903
Brief Title
Controlled Human Malaria Infection by Intradermal Injection of Plasmodium Falciparum Sporozoites in Tanzanian Adults
Official Title
Controlled Human Malaria Infection by Intradermal Injection of Plasmodium Falciparum Sporozoites (PfSPZ Challenge)in Tanzanian Adults
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
August 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanaria Inc.
Collaborators
Ifakara Health Research and Development Centre, Swiss Tropical & Public Health Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The proposed trial will evaluate whether relatively non immune populations in endemic countries can be effectively infected with aseptic, purified, cryopreserved sporozoites (PfSPZ Challenge) given intradermally.
Detailed Description
Controlled human malaria infection (CHMI) is a critical component of malaria vaccine and drug development and is an important element of any strategy for accelerating the development of new tools for malaria control, elimination and eradication. Until now, CHMI has been performed in malaria naïve subjects from countries not endemic for malaria using both infectious mosquitoes and recently, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ). Results from these studies report significant infection success in all study subjects and an excellent safety profile. The conduct of CHMI studies in malaria endemic populations will allow early understanding of responses to new vaccines and drugs in endemic country populations and for direct comparisons between previously exposed and non-exposed individuals. Performing CHMI studies in malaria endemic countries will reduce associated costs, speed-up the process of testing and substantially contribute to the acceleration of the malaria vaccine and drug research and development processes. This study to be conducted in Bagamoyo, Tanzania, aims to see whether people in endemic countries with minimal previous history of malaria are suitable for CHMI using PfSPZ Challenge. This study will also assess whether the success rate of the experiment is improved by lowering the volume of injection and increasing the number of inoculations. Hence, the study will contribute towards improvements in the CHMI studies using syringe and needle inoculation of sporozoites.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
Malaria Challenge, Plasmodium falciparum, PfSPZ Challenge, Controlled, human, malaria infection

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1 10,000 PfSPZ
Arm Type
Experimental
Arm Description
12 volunteers, ID PfSPZ Challenge total dose 10,000 PfSPZ administered by 2 injections of 50µL each.
Arm Title
Group 2 25,000 PfSPZ
Arm Type
Experimental
Arm Description
12 volunteers, ID PfSPZ Challenge total dose 25,000 PfSPZ administered in 4 injections of 10µL each.
Arm Title
Controls - saline
Arm Type
Placebo Comparator
Arm Description
4 Volunteers, ID saline administered in 2 injections of 50µL each and 2 volunteers, ID saline administered in 4 injections of 10µL each.
Intervention Type
Biological
Intervention Name(s)
PfSPZ Challenge
Other Intervention Name(s)
Plasmodium falciparum sporozoites
Intervention Description
Aseptic, purified, vialed, cryopreserved, fully infectious NF54 Plasmodium falciparum sporozoites (PfSPZ Challenge)
Intervention Type
Biological
Intervention Name(s)
Saline
Intervention Description
Saline
Primary Outcome Measure Information:
Title
Number of volunteers positive in each group through day 28 of follow up.
Description
Thick smears will be performed according to a standard operating procedure. In short, 15 μL of whole blood will be distributed on standardized 3-well slides, providing an equal slide thickness for all smears. Slides are dried and stained with Giemsa. 200 fields per slide will be read at 1000X. Slides are considered positive if they contain 2 or more parasites per 200 fields.
Time Frame
5 to 28 days
Secondary Outcome Measure Information:
Title
Time from inoculation until first positive parasitemia by thick smear in each volunteer in the two groups.
Time Frame
5-28 days
Title
Time from inoculation to until first positive parasitemia by qRT-PCR in each volunteer in the two groups.
Description
qRT-PCR will be performed according to standard procedure described in Hermsen et al. Mol. Biochem. Parasitol. 2001; 118: 247-251. In short, qRT-PCR will be performed on the multicopy 18S ribosomal RNA gene. Cultured P. falciparum ring stage parasites are taken as a positive control. All samples are spiked with murine white blood cells, and a murine albumin gene PCR is used to determine efficacy of DNA isolation.
Time Frame
5-28 days
Title
Kinetics of parasitemia in positive volunteers in the two groups as measured by qRT-PCR.
Description
Thick smear, malaria rapid diagnostic test and qRT-PCR samples will be taken from the same 3 mL EDTA vacutainer tube. Histidine Rich Protein 2 based malaria rapid diagnostic tests will be used in parallel to thick smears.
Time Frame
5-28 days
Title
Occurrence or intensity of signs or symptoms in the two groups of volunteers
Description
Signs and symptoms will be recorded at all visits and whenever a trial volunteer reports signs or symptoms to the trial physician between visits. The following signs and symptoms will be solicited: fever, headache, malaise, fatigue, myalgia, arthralgia, nausea, vomiting, chills, diarrhea, abdominal pain (Verhage, Telgt, Bousema, Hermsen, van Gemert, van der Meer, & Sauerwein 2005), chest pain, palpitations and shortness of breath.
Time Frame
5 days to 6 months

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy Male aged between 20-35 years, healthy volunteers Good Health status based on history & clinical examination Residing in or near DaresSalaam Willing to contribute to science in Tanzania Free from malaria parasite by blood smear & qRT-PCR Not suffering from any chronic illness including HIV/AIDS No documented history of malaria infection for the past 5 yrs Able & willing to come for complete one year follow up including minimum of three weeks of hospitalization All volunteers must sign the informed consent form & answer correctly 15 out 15 questions demonstrating their understanding of the meaning & procedures of the study Volunteer agrees to inform study doctor & agrees to release medical information concerning contra-indications for participation in the study Living with a third party that will contact the study team if in case of alteration of consciousness during the first month of the study Willing to undergo a Pf sporozoite challenge. Willing to take curative treatment for malaria (Coartem®) & any other medication which may be prescribed by a study doctor during study period All volunteers agree to stay in the hospital during parts of the study (overnight after challenge, up to 15 days during follow up & 3 days of Coartem® treatment) Reachable (24/7) by mobile phone during the whole study period Agreement not to participate in another study during the study period. Agreement not to donate blood during the study period. Available to attend all study visits Willingness to undergo HIV, hepatitis B & hepatitis C tests Exclusion Criteria: History of malaria in the past 5 yrs Plans to travel outside the Dar-es-salaam or Coast Region in first month (day 0-28) of the study Plans to travel to highly malarious areas in the 6 months following the study period Previous participation in malaria vaccine study &/or positive serology for Plasmodium falciparum asexual crude extract antibodies above acceptable cut off established for the site. History of arrhythmias or prolonged QT-interval or other cardiac disease Positive family history of in the 1st & 2nd degree relative for cardiac disease <50 yrs old. Volunteers unable to read & write in English & give written informed consent Previous history of drug or alcohol abuse interfering with normal social function A history of psychiatric disease The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (inhaled & topical corticosteroids are allowed) & during the study period A history or confirmed sickle cell anemia, sickle cell trait, thalassemia , thalassemia trait or G6PD deficiency Co-worker of the Ifakara Health Institute Symptoms, physical signs & laboratory values suggestive of systemic disorders including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, & other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers History of diabetes mellitus or cancer An estimated, ten year risk of fatal cardiovascular disease of <5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system Clinically significant abnormalities in electrocardiogram at screening Body Mass Index below 18 or above 30kg/m2 Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis or electrolytes Positive HIV, Hepatitis B virus or Hepatitis C Virus tests Participation in any other clinical study within 30 days prior to the onset of the study or during the study period Volunteers unable to be closely followed for social, geographic or psychological reasons Known hypersensitivity of other contra-indications to Coaterm® or Malarone® including treatment taken by the volunteer that interferes with Coartem® or Malarone® Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Salim Abdulla, MD, PhD
Organizational Affiliation
Ifakara Health Institute (IHI), Tanzania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bagamoyo Research and Training Center, Ifakara Health Institute
City
Bagamoyo
Country
Tanzania

12. IPD Sharing Statement

Citations:
PubMed Identifier
25070995
Citation
Shekalaghe S, Rutaihwa M, Billingsley PF, Chemba M, Daubenberger CA, James ER, Mpina M, Ali Juma O, Schindler T, Huber E, Gunasekera A, Manoj A, Simon B, Saverino E, Church LWP, Hermsen CC, Sauerwein RW, Plowe C, Venkatesan M, Sasi P, Lweno O, Mutani P, Hamad A, Mohammed A, Urassa A, Mzee T, Padilla D, Ruben A, Sim BKL, Tanner M, Abdulla S, Hoffman SL. Controlled human malaria infection of Tanzanians by intradermal injection of aseptic, purified, cryopreserved Plasmodium falciparum sporozoites. Am J Trop Med Hyg. 2014 Sep;91(3):471-480. doi: 10.4269/ajtmh.14-0119. Epub 2014 Jul 28.
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Controlled Human Malaria Infection by Intradermal Injection of Plasmodium Falciparum Sporozoites in Tanzanian Adults

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