Phase 1/2a Trial of Pf GAP p52-/p36- Sporozoite Malaria Vaccine

Tracking Information
First Submitted Date ICMJE	December 1, 2009
First Posted Date ICMJE	December 3, 2009
Last Update Posted Date	May 30, 2013
Study Start Date ICMJE	March 2010
Actual Primary Completion Date	June 2011 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 1, 2009)	Occurrence of solicited adverse events (AE) [ Time Frame: From administration of study vaccine through 7 days (± 1 days) post dosing ]; Occurrence of unsolicited AEs [ Time Frame: From administration of study vaccine through 28 days (± 4 days) post dosing ]; Occurrence of laboratory adverse events (AE) [ Time Frame: From administration of study vaccine through 7 days (± 1 days) post dosing ]; Detection of breakthrough peripheral parasitemia by thick blood film [ Time Frame: From 7 days after administration of vaccine through 28 days (+ 4 days) post-dosing ]; Occurrence of serious adverse events (SAE) [ Time Frame: From administration of study vaccine through the duration of the trial ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01024686 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 1, 2009)	Development of parasitemia and time to parasitemia after primary malaria challenge following administration of GAP [ Time Frame: From administration of study vaccine through the duration of the trial ]; Development of parasitemia and time to parasitemia after re-challenge following administration of GAP [ Time Frame: From administration of study vaccine through the duration of the trial ]; P. falciparum specific cell-mediated immune responses [ Time Frame: From administration of study vaccine through the duration of the trial ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Phase 1/2a Trial of Pf GAP p52-/p36- Sporozoite Malaria Vaccine
Official Title ICMJE	Phase 1/2a Trial to Assess the Safety, Immunogenicity and Efficacy of Genetically-attenuated Plasmodium Falciparum Parasites p52-/p36- (GAP) Vaccine, Administered by Bite of Infected Anopheles Mosquito to Malaria-naïve Adults Living in the United States.
Brief Summary	The purpose of this study is to assess safety and tolerability of escalating doses of a genetically attenuated parasite malaria vaccine (p52-/p36- GAP vaccine) in healthy malaria-naive adults. The study will also assess preliminary efficacy of p52-/p36- GAP vaccine following primary experimental challenge with P. falciparum sporozoites. Lastly, the study will assess immunogenicity of p52-/p36- GAP in malaria-naïve healthy adults and preliminary efficacy of p52-/p36- GAP vaccine following primary experimental re-challenge with P. falciparum sporozoites.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1; Phase 2
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention
Condition ICMJE	Malaria
Intervention ICMJE	Biological: p52-/p36- GAP Vaccine Administered by five bites from GAP-infected Anopheles mosquito; Biological: p52-p36- GAP Vaccine Administered by 200 bites from GAP-infected Anopeles mosquito; Biological: p52-/p36- GAP Vaccine Five doses separated by 4-weeks, each administered by 200 bites from GAP-infected Anopheles mosquito
Study Arms	Experimental: p52-p36- GAP Vaccine Interventions: Biological: p52-/p36- GAP Vaccine Biological: p52-p36- GAP Vaccine; No Intervention: Infectivity Control; Experimental: p52-p36- GAP Vaccine + Infectivity Challenge Intervention: Biological: p52-/p36- GAP Vaccine
Publications *	Spring M, Murphy J, Nielsen R, Dowler M, Bennett JW, Zarling S, Williams J, de la Vega P, Ware L, Komisar J, Polhemus M, Richie TL, Epstein J, Tamminga C, Chuang I, Richie N, O'Neil M, Heppner DG, Healer J, O'Neill M, Smithers H, Finney OC, Mikolajczak SA, Wang R, Cowman A, Ockenhouse C, Krzych U, Kappe SH. First-in-human evaluation of genetically attenuated Plasmodium falciparum sporozoites administered by bite of Anopheles mosquitoes to adult volunteers. Vaccine. 2013 Oct 9;31(43):4975-83. doi: 10.1016/j.vaccine.2013.08.007. Epub 2013 Sep 8.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Actual Enrollment ICMJE; (submitted: May 28, 2013)	6
Original Estimated Enrollment ICMJE; (submitted: December 1, 2009)	32
Actual Study Completion Date	June 2011
Actual Primary Completion Date	June 2011 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: A male or non-pregnant, non-lactating female 18 to 50 years of age (inclusive) at the time of enrollment; Free of significant health problems as established by medical history, laboratory assessment and clinical examination before entering into the study; Volunteers must have low cardiac risk factors according to the NHANES I criteria and a non-significant electrocardiogram (EKG) as determined by a expert consultant cardiologist; Available to participate for duration of study; Reproductive status: a female participant must:; not be of reproductive potential: i.e. be surgically, medically or physiologically sterile, or; if engages in sexual activity that could lead to pregnancy:; agrees to consistently use contraception until 2 months after the last protocol visit. Contraception is defined as using 1 of the following methods:; condoms (male or female) with or without a spermicide; diaphragm or cervical cap with spermicide; intrauterine device (IUD); hormonal contraception; If the volunteer indicates he/she is active duty military (on the DCT sign-in page and intake form), approval from their supervisor through the Division Director using the Statement of Supervisor's Approval Form must be signed and on file prior to receipt of any test product; Written informed consent must be obtained from the subject before screening procedures; Prior to entry into this study, subjects must score at least 80% correct on a 10- question multiple-choice quiz that assesses their understanding of this study. Exclusion Criteria: Prior receipt of any investigational malaria vaccine; Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period; Administration of any vaccine within 30 days of first study vaccination Any past history of malaria; Planned travel to malarious areas during the study period; Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection; A family history of congenital or hereditary immunodeficiency; Moderate or high 5-year cardiovascular risk as determined by NHANES 1 model; An abnormal 12-lead electrocardiogram (EKG) suggestive of cardiac disease as determined by a clinician; Seropositive for HIV, Hepatitis C virus (antibodies to HCV) and/or HBsAg; Hepatomegaly, right upper quadrant abdominal pain or tenderness; History of splenectomy; Chronic or active neurologic disease including seizure disorder and chronic migraine headaches; History of psoriasis and porphyria; Acute or chronic, clinically significant pulmonary, cardiovascular, ocular, hematologic, hepatic or renal functional abnormality, as determined by physical examination or abnormal baseline laboratory screening tests and medical history review; Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of vaccination. For corticosteroids, this is defined as prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed.; Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period; Current chronic use of medications known to cause drug reactions with chloroquine and/or atovaquone/proguanil such as cimetidine and metoclopramide.; Current chronic use or use within one month prior to enrollment of antibiotics with anti-malarial effects such as tetracyclines for acne, sulfa drugs for recurrent urinary tract infections, etc.; Pregnant or lactating female; Female who is willing or intends to become pregnant during the study and for two (2) months after study completion; Any history of allergic reaction or anaphylaxis to previous vaccination; History of severe reactions to mosquito bites.; Inability to make follow-up visits or complete diary cards; Suspected or known current alcohol abuse/drug abuse as obtained by history and physical examination; Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 50 Years (Adult)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01024686
Other Study ID Numbers ICMJE	WR 1584
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Seattle Biomedical Research Institute
Study Sponsor ICMJE	Seattle Biomedical Research Institute
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Michele Spring, M.D. Walter Reed Army Institute of Research (WRAIR)
PRS Account	Seattle Biomedical Research Institute
Verification Date	May 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP