MalariaPhase 1NCT01540903
Controlled Human Malaria Infection by Intradermal Injection of Plasmodium Falciparum Sporozoites in Tanzanian Adults
A Phase 1 study testing PfSPZ Challenge and Saline in people with Malaria, run by Sanaria Inc. at 1 site in Tanzania.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- PfSPZ Challenge and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteTanzania
- Study dates
- Feb 2012to Aug 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
Tanzania1 site
Bagamoyo Research and Training Center, Ifakara Health Institute
Bagamoyo
About this study
Official title: Controlled Human Malaria Infection by Intradermal Injection of Plasmodium Falciparum Sporozoites (PfSPZ Challenge)in Tanzanian Adults
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.
Read the 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.
- Conditions
- Malaria
- Being tested
- PfSPZ Challenge, Saline
- Keywords
- Malaria Challenge, Plasmodium falciparum, PfSPZ Challenge, Controlled, human, malaria infection
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PfSPZ ChallengeBiological
Also called Plasmodium falciparum sporozoites
Aseptic, purified, vialed, cryopreserved, fully infectious NF54 Plasmodium falciparum sporozoites (PfSPZ Challenge)
SalineBiological
Saline
| Study group | Role | What they receive |
|---|---|---|
| Group 1 10,000 PfSPZ | Experimental | 12 volunteers, ID PfSPZ Challenge total dose 10,000 PfSPZ administered by 2 injections of 50µL each. Receives: Biological: PfSPZ Challenge |
| Group 2 25,000 PfSPZ | Experimental | 12 volunteers, ID PfSPZ Challenge total dose 25,000 PfSPZ administered in 4 injections of 10µL each. Receives: Biological: PfSPZ Challenge |
| Controls - saline | Placebo comparator | 4 Volunteers, ID saline administered in 2 injections of 50µL each and 2 volunteers, ID saline administered in 4 injections of 10µL each. Receives: Biological: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 to 28 days
Secondary outcomes (4)
Time from inoculation until first positive parasitemia by thick smear in each volunteer in the two groups.
Measured: 5-28 days
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.
Measured: 5-28 days
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.
Measured: 5-28 days
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.
Measured: 5 days to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2012 (estimated)
- Study startFeb 2012
- Primary completionSep 2012
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanaria Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ifakara Health Research and Development Centre, Swiss Tropical & Public Health Institute
- Responsible party
- Sponsor
- Investigators
- Salim Abdulla, MD, PhD, Principal investigator, Ifakara Health Institute (IHI), Tanzania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01540903
- Sponsor's protocol ID
- BSPZC1
- Status last verified
- Sep 2014
- First submitted
- 23 Feb 2012
- Last updated
- 10 Sep 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25070995
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Controlled Human Malaria Infection by Intradermal Injection of Plasmodium Falciparum Sporozoites (PfSPZ Challenge)in Tanzanian Adults
- ClinicalTrials.gov ID
- NCT01540903
- Acronym / sponsor ID
- BSPZC1
- Conditions
- Malaria
- Keywords
- Malaria Challenge, Plasmodium falciparum, PfSPZ Challenge, Controlled, human, malaria infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Sanaria Inc.Industry (pharma, biotech, devices)
- Collaborators
- Ifakara Health Research and Development Centre, Swiss Tropical & Public Health Institute
- Study start
- Feb 2012
- Primary completion
- Sep 2012 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 29 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 10,000 PfSPZ | Experimental | Biological: PfSPZ Challenge12 volunteers, ID PfSPZ Challenge total dose 10,000 PfSPZ administered by 2 injections of 50µL each. |
| Group 2 25,000 PfSPZ | Experimental | Biological: PfSPZ Challenge12 volunteers, ID PfSPZ Challenge total dose 25,000 PfSPZ administered in 4 injections of 10µL each. |
| Controls - saline | Placebo comparator | Biological: Saline4 Volunteers, ID saline administered in 2 injections of 50µL each and 2 volunteers, ID saline administered in 4 injections of 10µL each. |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PfSPZ ChallengeAlso: Plasmodium falciparum sporozoitesAseptic, purified, vialed, cryopreserved, fully infectious NF54 Plasmodium falciparum sporozoites (PfSPZ Challenge) | Biological | Group 1 10,000 PfSPZ, Group 2 25,000 PfSPZ |
| SalineSaline | Biological | Controls - saline |
Primary outcome
Number of volunteers positive in each group through day 28 of follow up.
Time frame: 5 to 28 days
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.
4 secondary outcomes
Time from inoculation until first positive parasitemia by thick smear in each volunteer in the two groups.
Time frame: 5-28 days
Time from inoculation to until first positive parasitemia by qRT-PCR in each volunteer in the two groups.
Time frame: 5-28 days
Kinetics of parasitemia in positive volunteers in the two groups as measured by qRT-PCR.
Time frame: 5-28 days
Occurrence or intensity of signs or symptoms in the two groups of volunteers
Time frame: 5 days to 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2014.
- Results publication: PubMed 25070995Shekalaghe 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Salim Abdulla, MD, PhD principal investigator
Ifakara Health Institute (IHI), Tanzania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PfSPZ Challenge and Saline in people with Malaria, run by Sanaria Inc. at 1 site in Tanzania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of volunteers positive in each group through day 28 of follow up. (time frame: 5 to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01540903, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2014.