Development of a Skin Test for the Na-ASP-2 Hookworm Antigen

Allergy Clinical Trial

Official title:

Development of a Skin Test to Detect Immediate-type Hypersensitivity to the Experimental Na-ASP-2 Hookworm Antigen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00603889
• Other study ID #: SVI-07-02
• Status: Completed
• Phase: N/A
• First received: January 17, 2008
• Last updated: January 18, 2012
• Start date: March 2008
• Est. completion date: May 2008

Study information

• Verified date: January 2012
• Source: Albert B. Sabin Vaccine Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Na-ASP-2 is a protein expressed during the larval stage of the N. americanus hookworm life cycle. In a clinical study in previously hookworm-infected adults in Brazil, this protein induced urticarial reactions (rash) in a subset of volunteers. This study will evaluate solutions of varying concentrations of the protein in both a skin prick-puncture and intradermal test that will eventually be used to screen volunteers living in hookworm endemic areas who are being considered as potential participants in vaccine trials, to reduce the potential of inducing allergic reactions in those vaccinated with the Na-ASP-2 Hookworm Vaccine.

Description:

• Study site: George Washington University Medical Center

• Number of participants: up to 15

• Study duration: up to 3 months; each participant will undergo a minimum of one screening visit and one study visit.

• Each participant will have both skin prick-puncture and intradermal skin tests applied on the same study day. The prick-puncture and intradermal tests will be applied sequentially to the volar aspects of the participant's forearms:

1. Skin prick-puncture: four different concentrations of Na-ASP-2 solution (1, 10, 100, and 1000 μg/mL) will be applied simultaneously in duplicate, to the left forearm.

2. Intradermal: three different concentrations of Na-ASP-2 (10, 100, and 1000 μg/mL) will be injected simultaneously, in duplicate, to the right forearm.

3. Allergen diluent and histamine solutions will be utilized as the negative and positive controls, respectively, for both the skin prick-puncture and intradermal tests.

4. Participants will be observed in the study clinic for at least 30 minutes following application of the skin tests, and will be contacted via telephone 2 days following skin testing.

5. Sizes of the wheal and erythema reactions for each application will be recorded and graded in comparison to the histamine positive control reaction.

• Each participant will have blood collected via venipuncture (a maximum of 25 mL) immediately prior to application of the skin tests, in order to measure antibodies (particularly IgG and IgE) to Na-ASP-2 using an ELISA procedure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Males or females between 18 and 45 years of age, inclusive.

• Good general health as determined by means of the screening procedure.

• Willingness to participate in the study as evidenced by signing the informed consent document.

Exclusion Criteria:

• History of previous infection with hookworm.

• Prior extensive and continuous travel, work, or residence (> 1 month) in a hookworm-endemic region.

• Pregnancy as determined by a positive urine hCG test (if female).

• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history or physical examination.

• Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the volunteer to understand and cooperate with the study protocol.

• Other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol.

• Participation in an investigational vaccine or drug trial within 14 days of starting this study.

• Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.

• History of a severe allergic reaction or anaphylaxis.

• Known immunodeficiency syndrome.

• Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study.

• History of a surgical splenectomy.

• Extensive dermatitis precluding skin testing

• Current use of a beta blocker (oral or topical) or anti-histamine medication. A volunteer may participate in the study if they agree to withhold use of an anti-histamine for at least 5 days prior to application of the skin test.

• Use of a tricyclic anti-depressant within the past month.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Allergy
• Hookworm Infection
• Hookworm Infections

Intervention

Biological:
• Na-ASP-2 Skin Test Reagent
Na-ASP-2 Hookworm Skin Test Reagent, 1-1000 mcg/mL solution

Locations

Country	Name	City	State
United States	GWUMC Clinical Trials Unit	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Albert B. Sabin Vaccine Institute

Country where clinical trial is conducted

United States, 

References & Publications (3)

Diemert DJ, Bethony JM, Hotez PJ. Hookworm vaccines. Clin Infect Dis. 2008 Jan 15;46(2):282-8. doi: 10.1086/524070. Review. — View Citation

Fujiwara RT, Bethony J, Bueno LL, Wang Y, Ahn SY, Samuel A, Bottazzi ME, Hotez P, Mendez S. Immunogenicity of the hookworm Na-ASP-2 vaccine candidate: characterization of humoral and cellular responses after vaccination in the Sprague Dawley rat. Hum Vaccin. 2005 May-Jun;1(3):123-8. Epub 2005 May 20. — View Citation

Goud GN, Bottazzi ME, Zhan B, Mendez S, Deumic V, Plieskatt J, Liu S, Wang Y, Bueno L, Fujiwara R, Samuel A, Ahn SY, Solanki M, Asojo OA, Wang J, Bethony JM, Loukas A, Roy M, Hotez PJ. Expression of the Necator americanus hookworm larval antigen Na-ASP-2 in Pichia pastoris and purification of the recombinant protein for use in human clinical trials. Vaccine. 2005 Sep 15;23(39):4754-64. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	100 Mcg/ml Na-ASP-2 Prick-puncture Skin Test	Mean grade of wheal reaction after 2 applications of the skin test reagent per participant. For each skin test reaction, the grade of the test was determined based on the mean of the longest and orthogonal diameters, which was then compared to the equivalent measurements of a histamine solution positive control that was applied at the same time as the test. Grading was as follows: 0 no discernible wheal; < ½ histamine diameter; = ½ histamine; < histamine diameter; = size of histamine control ± 1 mm; > histamine diameter; < 2x diameter; = 2x histamine control	15 minutes after skin test application	No
Secondary	1000 Mcg/ml Na-ASP-2 Prick-puncture Skin Test	Mean grade of wheal reaction after 2 applications of the skin test reagent per participant. For each skin test reaction, the grade of the test was determined based on the mean of the longest and orthogonal diameters, which was then compared to the equivalent measurements of a histamine solution positive control that was applied at the same time as the test. Grading was as follows: 0 no discernible wheal; < ½ histamine diameter; = ½ histamine; < histamine diameter; = size of histamine control ± 1 mm; > histamine diameter; < 2x diameter; = 2x histamine control	15 minutes after skin test application	No
Secondary	100 Mcg/ml Na-ASP-2 Intradermal Skin Test	Mean grade of wheal reaction after 2 applications of the skin test reagent per participant. For each skin test reaction, the grade of the test was determined based on the mean of the longest and orthogonal diameters, which was then compared to the equivalent measurements of a histamine solution positive control that was applied at the same time as the test. Grading was as follows: 0 no discernible wheal; < ½ histamine diameter; = ½ histamine; < histamine diameter; = size of histamine control ± 1 mm; > histamine diameter; < 2x diameter; = 2x histamine control	15 minutes after skin test application	No
Secondary	1000 Mcg/ml Na-ASP-2 Intradermal Skin Test	Mean grade of wheal reaction after 2 applications of the skin test reagent per participant. For each skin test reaction, the grade of the test was determined based on the mean of the longest and orthogonal diameters, which was then compared to the equivalent measurements of a histamine solution positive control that was applied at the same time as the test. Grading was as follows: 0 no discernible wheal; < ½ histamine diameter; = ½ histamine; < histamine diameter; = size of histamine control ± 1 mm; > histamine diameter; < 2x diameter; = 2x histamine control	15 minutes after skin test application	No