Malaria Challenge With NF54 Strain

NCT00744133 | Completed Phase 1

• 3 other identifiers: 05-0053Malaria CVD 17000N01AI80057C
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Plasmodium Falciparum Infection

Keywords

Plasmodium falciparum, NF54, Anopheles stephensi, mosquito, malaria

Outcome Measures

Primary Outcomes (4)

• Occurrence of a positive malaria smear after the malaria challenge.

  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.

  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.

  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.

  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).

  After malaria challenge during a 56-day surveillance period (day of challenge and days 5-28, 35, 42, 49 and 56 after challenge).

Study Arms (2)

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.

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.

Biological: NF54 P. falciparum isolate

Interventions

NF54 P. falciparum isolate BIOLOGICAL

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

Group 1: 1, 3, or 5 bites; Group 2: N bites

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Has an active neoplastic disease (excluding nonmelanotic skin cancer) or neoplastic disease within the past 5 years or any history of hematologic malignancy.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

University of Maryland School of Medicine - Center for Vaccine Development - Baltimore

Baltimore, Maryland, 21201-1509, United States

Location

Related Publications (2)

• 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.

  PMID: 23874828 BACKGROUND

• 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.

  PMID: 21042404 BACKGROUND

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2008
• First Posted: August 29, 2008
• Study Start: March 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: November 1, 2011
• Last Updated: August 8, 2014

Record last verified: 2014-07

Locations

US (1)