Plasmodium Falciparum InfectionPhase 1NCT00744133

Malaria Challenge With NF54 Strain

A Phase 1 study testing NF54 P. falciparum isolate in people with Plasmodium Falciparum Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for: Plasmodium Falciparum Infection
What is being tested?: NF54 P. falciparum isolate
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 37 participants
Where: 1 siteUnited States
Study dates: Mar 2009to Nov 2011
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 18 to 40 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Male or nonpregnant female between the ages of 18 and 40 years, inclusive.
Women who are not surgically sterile (no history of bilateral tubal ligation, bilateral salpingo-oophorectomy, or hysterectomy), post-menopausal (1 year without menses) or determined otherwise by medical evaluation to be sterile must agree to practice adequate contraception [such as double barrier methods (condoms plus foam or spermicide, diaphragm plus foam or spermicide), some intrauterine devices (IUDs), intravaginal or transdermal hormonal methods initiated at least 1 month prior to inoculation, or a vasectomized partner] for the entire study period (56 days). Serologic pregnancy tests will be conducted upon screening. Urine testing will be done on the day of malaria challenge, on the day of the first positive malaria smear and at the conclusion of active surveillance (Day 56).
Is in good health, as determined by vital signs (heart rate, blood pressure, oral temperature), medical history, screening 12-lead electrocardiogram (ECG) and a physical examination.
Has normal laboratory values [urinalysis (assessing blood and protein presence as greater than trace by dipstick), hemoglobin, white blood cells, platelet count, aspartate aminotransferase (AST), (alanine aminotransferase) ALT, glucose and creatinine] prior to challenge study.
Able to understand and comply with planned study procedures including an inpatient stay from Day 8-18 after malaria challenge.
Provides informed consent prior to any study procedures, correctly answers greater than or equal to 70 percent on the post consent quiz and is available for all study visits.
Willing to avoid non-study related blood donation for 3 years following Plasmodium falciparum challenge.

Who cannot join

Has any known history of malaria infection, is a long-term resident (> 5 years) of a malaria-endemic area, was born and resided in a malaria-endemic area, or has traveled to a malaria-endemic area within the previous 6 months.
Has a positive urine pregnancy test prior to malaria challenge (if female of childbearing potential), is lactating, or has the intention to become pregnant within 2 months after enrollment in this study.
Use of any antibiotic or antimalarial drug beginning 28 days prior to the screening and extending to Day 56 of study surveillance.
Has evidence of increased cardiovascular disease risk (defined as > 10 percent, 5 year risk) as determined by the method of Gaziano. Risk factors include sex, age (years), systolic blood pressure (mm Hg), smoking status (current versus past or never), body mass index (BMI) (kg/mm^2), reported diabetes status (yes/no), current treatment for raised blood pressure (yes/no).
Is immunosuppressed (e.g., poorly-controlled diabetes mellitus, cirrhosis, renal insufficiency, active malignancy, connective tissue disease, organ transplant) as a result of an underlying illness or treatment.
An abnormal electrocardiogram (EKG), defined as one showing pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm excluding isolated premature atrial contractions; right or left bundle branch block; or advanced (secondary or tertiary) A-V heart block.

Show all 23Show fewer

Has an active neoplastic disease (excluding nonmelanotic skin cancer) or neoplastic disease within the past 5 years or any history of hematologic malignancy.
Is using or intends to continue using oral or parenteral steroids, high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) or other immunosuppressive or cytotoxic drugs (an exception includes asthma for which any oral or inhaled steroid intake will mean exclusion from study enrollment).
Has a known active history of human immunodeficiency virus, hepatitis B surface antigen positivity, or hepatitis C infection.
Has a history of active alcohol or drug abuse in the last 5 years.
Has a history of receiving blood products within the 3 months prior to enrollment in this study.
Has a history of psoriasis or porphyria, which may be exacerbated after treatment with chloroquine.
Has an acute or chronic medical condition that, in the opinion of the investigator, would render malaria challenge unsafe or would interfere with the evaluation of responses (this includes, but is not limited to: known liver disease, renal disease, neurological disorders, visual field defects, cardiac disorders, pulmonary disorders, auditory damage, diabetes mellitus, and transplant recipients).
Has a history of anaphylactic response to mosquito bites or known allergy to chloroquine, 4-aminoquinoline derivatives [atovaquone/proguanil (Malarone®)], ibuprofen, or acetaminophen that may be used to treat volunteers developing malaria after Plasmodium falciparum challenge.
Is using or intends to continuing using a medication known to cause drug reactions with chloroquine or Malarone®, such as cimetidine, metoclopramide, antacids or kaolin (antacids and kaolin can be administered at least 4 hours from intake of chloroquine).
History of retinal or visual field changes, auditory damage, or seizures.
History of splenectomy.
Has known sickle cell trait or laboratory evidence of sickle cell trait.
Has an acute illness, including an oral temperature greater than 100.4 degrees Fahrenheit, within 1 week prior to malaria challenge.
Plans to undergo surgery (elective or otherwise) between enrollment and 4 weeks (28 days) post-challenge.
Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to enrollment in this study, or expects to receive an experimental agent during the 2-month post-challenge period.
Has a diagnosis of schizophrenia, bi-polar disease or other major psychiatric disease.
Has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Maryland School of Medicine - Center for Vaccine Development - Baltimore
Baltimore, Maryland, 21201-1509

Other trials in United States

About this study

Official title: An Interventional Plasmodium Falciparum Malaria Challenge Model Utilizing the NF54 Strain of Parasite Transmitted by Aseptic A. Stephensi Mosquitoes to Healthy Malaria-Naïve Adult Volunteers

The purpose of this study is to determine how many infected mosquito bites are required to reliably give volunteers a case of malaria. It is expected that volunteers will develop malaria and may have symptoms. Safety is the main concern. A malaria challenge is given by allowing a volunteer to receive 1, 3, or 5 mosquito's bites. Then participants are carefully followed and blood is tested. The study will also look at how immune systems (the cells and substances that protect the body from infection and foreign matter) respond after mosquito bite challenges. About 38 subjects (aged 18-40 years) from the greater Baltimore, Maryland (United States) community will participate and may stay overnight for 10 days at a local medical center. Procedures include medical screening, assignment to a dose group, a mosquito bite challenge, and 56 day follow-up. Volunteers will be contacted by telephone at 6 and 12 months after the malaria challenge.

Read the detailed description

This is a randomized trial of the aseptically raised anopheles mosquito malaria challenge. Adults aged 18-40 years will be randomized to one group of 18 subjects (Part A) or a second group of 20 subjects (Part B). Adults will be randomized to receive 1, 3 or 5 bites of Anopheles (A.) stephensi mosquitoes infected with the NF54 strain of chloroquine-sensitive Plasmodium (P.) falciparum. Part B will be informed by the results of Part A. Thus, a total of approximately 38 adults will receive a malaria challenge. The challenge for Part A will be given on day 0 with the subsequent group (Part B) commencing after a 56 day safety review. Solicited adverse events will be recorded on the days of malaria challenge, outpatient days 5-7, 19-28, 35, 42, 49, and 56 post-challenge event. Inpatient analysis will occur from Days 8-18 or until three-day directly observed therapy for P. falciparum infection is complete. Additional outpatient, post-malaria infection follow-up will occur weekly for 4 weeks. Unsolicited adverse events will be recorded for 56 days after each malaria challenge event. Participants will receive a telephone follow-up six and twelve months after enrollment. The primary objective is to develop and evaluate the safety and tolerability of a new human malaria challenge model using aseptically-raised anopheles mosquitoes infected with the NF54 isolate of P. falciparum and reared under current Good Manufacturing Practices (cGMPs) conditions. Secondary objectives are to obtain information on the minimum number of A. stephensi bites required to safely achieve 100 percent adult human volunteer infectivity (Malaria challenge, Part A); obtain information on the minimum quantity of A. stephensi bites in a second challenge study to achieve 100 percent adult human volunteer infectivity (Malaria challenge, Part B); develop molecular diagnostic techniques for rapid and accurate real-time diagnosis of P. falciparum infection to assess the role as a new diagnostic standard for P. falciparum challenge studies.

Conditions: Plasmodium Falciparum Infection
Being tested: NF54 P. falciparum isolate
Keywords: Plasmodium falciparum, NF54, Anopheles stephensi, mosquito, malaria
Medical subject headings: Malaria, Falciparum, Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NF54 P. falciparum isolateBiological
1, 3, 5 or N bites from aseptically-raised Anopheles stephensi female mosquitoes infected with Plasmodium falciparum parasites of the NF54 strain.

Study groups in NCT00744133
Study group	Role	What they receive
Group 1: 1, 3, or 5 bites	Experimental	Part A: 18 subjects receive 1, 3, or 5 bites of Anopheles stephensi mosquitoes infected with the NF54 strain of Plasmodium falciparum. Receives: Biological: NF54 P. falciparum isolate
Group 2: N bites	Experimental	Part B: 20 subjects receive N bites of Anopheles stephensi mosquitoes infected with the NF54 strain of Plasmodium falciparum. Receives: Biological: NF54 P. falciparum isolate

What is being measured

The primary outcome is the main question the study is designed to answer.

Occurrence of a positive malaria smear after the malaria challenge.
Measured: During a 56-day surveillance period (day of challenge and days 5-28, 35, 42, 49, and 56 after challenge).
Occurrence of serious adverse events.
Measured: After malaria challenge during a 56-day surveillance period (day of challenge and days 5-28, 35, 42, 49, and 56 after challenge) and 10 month follow-up period
Occurrence and severity of solicited symptoms.
Measured: 7 days after the malaria challenge and for the duration of follow-up after a malaria event (treatment days x 3 and smear-negative x 2 plus weekly follow-up x 4).
Occurrence and severity of unsolicited adverse events.
Measured: After malaria challenge during a 56-day surveillance period (day of challenge and 55 subsequent days. Volunteers will be questioned at Visits 2-29).

Secondary outcomes (1)

Occurrence of a positive real-time quantitative polymerase chain reaction (PCR).
Measured: After malaria challenge during a 56-day surveillance period (day of challenge and days 5-28, 35, 42, 49 and 56 after challenge).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2009Nov 2011

First posted29 Aug 2008 (estimated)
Study startMar 2009
Primary completionDec 2010
Study completionNov 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Plasmodium Falciparum InfectionStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
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
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00744133
Sponsor's protocol ID: 05-0053
Other IDs: Malaria CVD 17000, N01AI80057C
Status last verified: Jul 2014
First submitted: 28 Aug 2008
Last updated: 8 Aug 2014
Results posted: No

Publications

Laurens MB, Billingsley P, Richman A, Eappen AG, Adams M, Li T, Chakravarty S, Gunasekera A, Jacob CG, Sim BK, Edelman R, Plowe CV, Hoffman SL, Lyke KE. Successful human infection with P. falciparum using three aseptic Anopheles stephensi mosquitoes: a new model for controlled human malaria infection. PLoS One. 2013 Jul 16;8(7):e68969. doi: 10.1371/journal.pone.0068969. Print 2013.
PubMed 23874828
Lyke KE, Laurens M, Adams M, Billingsley PF, Richman A, Loyevsky M, Chakravarty S, Plowe CV, Sim BK, Edelman R, Hoffman SL. Plasmodium falciparum malaria challenge by the bite of aseptic Anopheles stephensi mosquitoes: results of a randomized infectivity trial. PLoS One. 2010 Oct 21;5(10):e13490. doi: 10.1371/journal.pone.0013490.
PubMed 21042404

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Interventional Plasmodium Falciparum Malaria Challenge Model Utilizing the NF54 Strain of Parasite Transmitted by Aseptic A. Stephensi Mosquitoes to Healthy Malaria-Naïve Adult Volunteers
ClinicalTrials.gov ID: NCT00744133
Acronym / sponsor ID: 05-0053
Conditions: Plasmodium Falciparum Infection
Keywords: Plasmodium falciparum, NF54, Anopheles stephensi, mosquito, malaria
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 37 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: Mar 2009
Primary completion: Dec 2010 (actual)
Study completion: Nov 2011 (actual)
First posted: 29 Aug 2008 (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.

Detailed description

Study design

Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Group 1: 1, 3, or 5 bites	Experimental	Biological: NF54 P. falciparum isolatePart A: 18 subjects receive 1, 3, or 5 bites of Anopheles stephensi mosquitoes infected with the NF54 strain of Plasmodium falciparum.
Group 2: N bites	Experimental	Biological: NF54 P. falciparum isolatePart B: 20 subjects receive N bites of Anopheles stephensi mosquitoes infected with the NF54 strain of Plasmodium falciparum.

Who may qualify

Ages: 18 to 40 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Male or nonpregnant female between the ages of 18 and 40 years, inclusive.
Women who are not surgically sterile (no history of bilateral tubal ligation, bilateral salpingo-oophorectomy, or hysterectomy), post-menopausal (1 year without menses) or determined otherwise by medical evaluation to be sterile must agree to practice adequate contraception [such as double barrier methods (condoms plus foam or spermicide, diaphragm plus foam or spermicide), some intrauterine devices (IUDs), intravaginal or transdermal hormonal methods initiated at least 1 month prior to inoculation, or a vasectomized partner] for the entire study period (56 days). Serologic pregnancy tests will be conducted upon screening. Urine testing will be done on the day of malaria challenge, on the day of the first positive malaria smear and at the conclusion of active surveillance (Day 56).
Is in good health, as determined by vital signs (heart rate, blood pressure, oral temperature), medical history, screening 12-lead electrocardiogram (ECG) and a physical examination.
Has normal laboratory values [urinalysis (assessing blood and protein presence as greater than trace by dipstick), hemoglobin, white blood cells, platelet count, aspartate aminotransferase (AST), (alanine aminotransferase) ALT, glucose and creatinine] prior to challenge study.
Able to understand and comply with planned study procedures including an inpatient stay from Day 8-18 after malaria challenge.

Key exclusion criteria (23 listed)

Has any known history of malaria infection, is a long-term resident (> 5 years) of a malaria-endemic area, was born and resided in a malaria-endemic area, or has traveled to a malaria-endemic area within the previous 6 months.
Has a positive urine pregnancy test prior to malaria challenge (if female of childbearing potential), is lactating, or has the intention to become pregnant within 2 months after enrollment in this study.
Use of any antibiotic or antimalarial drug beginning 28 days prior to the screening and extending to Day 56 of study surveillance.
Has evidence of increased cardiovascular disease risk (defined as > 10 percent, 5 year risk) as determined by the method of Gaziano. Risk factors include sex, age (years), systolic blood pressure (mm Hg), smoking status (current versus past or never), body mass index (BMI) (kg/mm^2), reported diabetes status (yes/no), current treatment for raised blood pressure (yes/no).
Is immunosuppressed (e.g., poorly-controlled diabetes mellitus, cirrhosis, renal insufficiency, active malignancy, connective tissue disease, organ transplant) as a result of an underlying illness or treatment.

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
NF54 P. falciparum isolate1, 3, 5 or N bites from aseptically-raised Anopheles stephensi female mosquitoes infected with Plasmodium falciparum parasites of the NF54 strain.	Biological	Group 1: 1, 3, or 5 bites, Group 2: N bites

Primary outcome

Occurrence of a positive malaria smear after the malaria challenge.
Time frame: During a 56-day surveillance period (day of challenge and days 5-28, 35, 42, 49, and 56 after challenge).
Occurrence of serious adverse events.
Time frame: After malaria challenge during a 56-day surveillance period (day of challenge and days 5-28, 35, 42, 49, and 56 after challenge) and 10 month follow-up period
Occurrence and severity of solicited symptoms.
Time frame: 7 days after the malaria challenge and for the duration of follow-up after a malaria event (treatment days x 3 and smear-negative x 2 plus weekly follow-up x 4).
Occurrence and severity of unsolicited adverse events.
Time frame: After malaria challenge during a 56-day surveillance period (day of challenge and 55 subsequent days. Volunteers will be questioned at Visits 2-29).

1 secondary outcome

Occurrence of a positive real-time quantitative polymerase chain reaction (PCR).
Time frame: After malaria challenge during a 56-day surveillance period (day of challenge and days 5-28, 35, 42, 49 and 56 after challenge).

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 8 Aug 2014.
Background: PubMed 23874828Laurens MB, Billingsley P, Richman A, Eappen AG, Adams M, Li T, Chakravarty S, Gunasekera A, Jacob CG, Sim BK, Edelman R, Plowe CV, Hoffman SL, Lyke KE. Successful human infection with P. falciparum using three aseptic Anopheles stephensi mosquitoes: a new model for controlled human malaria infection. PLoS One. 2013 Jul 16;8(7):e68969. doi: 10.1371/journal.pone.0068969. Print 2013.
Background: PubMed 21042404Lyke KE, Laurens M, Adams M, Billingsley PF, Richman A, Loyevsky M, Chakravarty S, Plowe CV, Sim BK, Edelman R, Hoffman SL. Plasmodium falciparum malaria challenge by the bite of aseptic Anopheles stephensi mosquitoes: results of a randomized infectivity trial. PLoS One. 2010 Oct 21;5(10):e13490. doi: 10.1371/journal.pone.0013490.

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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.

The record lists no contact. Use the official record to reach the sponsor.

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 NF54 P. falciparum isolate in people with Plasmodium Falciparum Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

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 7 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 8 Aug 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 United States. 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. 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?

Occurrence of a positive malaria smear after the malaria challenge. (time frame: During a 56-day surveillance period (day of challenge and days 5-28, 35, 42, 49, and 56 after challenge).). The study lists 4 primary outcomes in all. 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 NCT00744133, which also lists 2 linked publications.

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 8 Aug 2014.