Prevalence of Hookworm Infection and Community Preparedness for Hookworm Vaccine Trials in Endemic Areas of Brazil

• Sponsor: Albert B. Sabin Vaccine Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00939198
• Collaborator: (none)
• Enrollment: 87
• Location: 1
• Arm: 1
• Duration (Months): 40
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief 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. The clinical trial component of this study involves skin testing for immediate-type hypersensitivity to the Na-ASP-2 Antigen. Both prick-puncture and intradermal tests will be applied.

Condition or Disease	Intervention/Treatment	Phase
Hookworm Infection	Biological: Na-ASP-2 Skin Test Reagent	N/A

Detailed Description

The clinical testing of the Na-ASP-2 Skin Test Reagent to detect Immediate-type hypersensitivity to the Na-ASP-2 hookworm antigen will be conducted as part of a larger, on-going observational study of the prevalence and intensity of hookworm infection currently underway in Brazil. Eligible adult participants (ages 18-45 years) in this observational study will be invited to undergo the skin testing procedure. Skin testing will only be performed if they agree and sign the supplemental informed consent form for this skin testing procedure.

• Study site: Americaninhas Vaccine Center, Americaninhas, Minas Gerais, Brazil

• Number of participants to be skin tested: approximately 150 adults

• Duration of the skin testing procedures: up to 1 month; each participant will undergo skin testing and a follow-up blood collection 21+/-7 days after skin testing.

• 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: three different concentrations of Na-ASP-2 solution (10, 100, and 1000 μg/mL) will be applied sequentially in duplicate, to the left forearm.

2. Intradermal: one concentration of Na-ASP-2 (100 μg/mL) will be injected, 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 examined 2 and 7 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, and between 2 and 4 weeks after skin testing, in order to measure antibodies (particularly IgG and IgE) to Na-ASP-2 using an ELISA procedure.

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Determination of Prevalence and Intensity of Hookworm Infection and Community Preparedness for Hookworm Vaccine Trials in Endemic Areas of Northeastern Minas Gerais, Brazil
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Na-ASP-2 Hookworm Antigen Skin Test All participants will be skin tested with Na-ASP-2 skin test reagent applied to their arms, using both the prick-puncture and intradermal techniques.	Biological: Na-ASP-2 Skin Test Reagent; Na-ASP-2 Hookworm Skin Test Reagent, 1-1000 mcg/mL solution

Outcome Measures

Primary Outcome Measures

1. Size of Wheal Diameter at Site of Skin Test Application, Measured 15 Minutes After Injection [15 minutes after skin test application]

Secondary Outcome Measures

1. Anti-Na-ASP-2 IgE Antibody Level on Day of Skin Test Reaction [Upon skin testing]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Males and females between 6 and 45 years of age, inclusive, at the time of consenting to the parent study.

• Age greater than or equal to 18 years at the time of signing the supplemental informed consent document for the skin test procedure (parent study).

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

Exclusion Criteria:

• Inability to correctly answer all questions on the informed consent comprehension questionnaire.

• Attends school or works full-time outside of the study area.

• 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 to participate in the trial or would render the subject unable to comply with the protocol.

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

• Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of planned skin test application.

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centro de Pesquisas Rene Rachou	Belo Horizonte	Minas Gerais	Brazil

Sponsors and Collaborators

• Albert B. Sabin Vaccine Institute

Investigators

• Principal Investigator: Jeffrey Bethony, PhD, Albert B. Sabin Vaccine Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

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

• Responsible Party: Albert B. Sabin Vaccine Institute
• ClinicalTrials.gov Identifier: NCT00939198
• Other Study ID Numbers: SVI-06-01
• First Posted: Jul 14, 2009
• Last Update Posted: Aug 1, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Albert B. Sabin Vaccine Institute: Hookworm; Allergy; Vaccine; Skin Test; Immediate-type hypersensitivity to Na-ASP-2 hookworm antigen
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hookworm Infections; Ancylostomiasis

Study Results

Participant Flow

Arm/Group Title	Na-ASP-2 Hookworm Antigen Skin Test
Arm/Group Description	All participants will be skin tested with Na-ASP-2 skin test reagent (1000 mcg/ml recombinant Na-ASP-2) applied to their arms, using both the prick-puncture and intradermal techniques.
Period Title: Overall Study
STARTED	87
COMPLETED	87
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Na-ASP-2 Hookworm Antigen Skin Test
Arm/Group Description	All participants will be skin tested with Na-ASP-2 skin test reagent (1000 mcg/ml recombinant Na-ASP-2) applied to their arms, using both the prick-puncture and intradermal techniques.
Overall Participants	87
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	87 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	48 55.2%
Male	39 44.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	87 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Brazil	87 100%

Outcome Measures

1. Primary Outcome

Title	Size of Wheal Diameter at Site of Skin Test Application, Measured 15 Minutes After Injection
Time Frame	15 minutes after skin test application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Na-ASP-2 Hookworm Antigen Skin Test
Arm/Group Description	All participants will be skin tested with Na-ASP-2 skin test reagent applied to their arms, using both the prick-puncture and intradermal techniques. Na-ASP-2 Skin Test Reagent: Na-ASP-2 Hookworm Skin Test Reagent, 1-1000 mcg/mL solution
Measure Participants	87
Median (Inter-Quartile Range) [cm]	3.5

2. Secondary Outcome

Title	Anti-Na-ASP-2 IgE Antibody Level on Day of Skin Test Reaction
Time Frame	Upon skin testing

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Na-ASP-2 Hookworm Antigen Skin Test
Arm/Group Description	All participants will be skin tested with Na-ASP-2 skin test reagent (1000 mcg/ml recombinant Na-ASP-2) applied to their arms, using both the prick-puncture and intradermal techniques.
Measure Participants	42
Median (Inter-Quartile Range) [kU/L]	1.89

Adverse Events

Arm/Group Title	Na-ASP-2 Hookworm Antigen Skin Test
Arm/Group Description	All participants will be skin tested with Na-ASP-2 skin test reagent (1000 mcg/ml recombinant Na-ASP-2) applied to their arms, using both the prick-puncture and intradermal techniques.
All Cause Mortality
	Na-ASP-2 Hookworm Antigen Skin Test
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Na-ASP-2 Hookworm Antigen Skin Test
	Affected / at Risk (%)	# Events
Total	0/87 (0%)
Other (Not Including Serious) Adverse Events
	Na-ASP-2 Hookworm Antigen Skin Test
	Affected / at Risk (%)	# Events
Total	0/87 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.