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Experimental Infection of Hookworm-naïve Adults With Dermally-applied Infectious Necator Americanus Hookworm Larvae

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ClinicalTrials.gov Identifier: NCT01940757
Recruitment Status : Recruiting
First Posted : September 12, 2013
Last Update Posted : January 10, 2023
Sponsor:
Information provided by (Responsible Party):
Maria Elena Bottazzi PhD, Baylor College of Medicine

Study Description
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Brief Summary:
An experimental hookworm infection model is being developed to provide early proof-of-concept that a hookworm vaccine targeting the blood-feeding pathway of adult hookworms is feasible and efficacious. The proposed model consists of vaccinating healthy, hookworm-naïve adults with a candidate hookworm vaccine, followed by challenging them with the investigational product, Necator americanus Larval Inoculum to assess the effect of vaccination on infection. The first proposed study will be a feasibility study that will consist of administering different doses of the Necator americanus Larval Inoculum to healthy adult volunteers to determine the optimal dose (i.e., number of infectious larvae) that is safe, well-tolerated and results in consistent infection.

Condition or disease Intervention/treatment Phase
Hookworm Infection Biological: Necator americanus Hookworm Larvae Phase 1

Detailed Description:

Open-label, dose-escalation clinical study in healthy, hookworm-naïve adults:

  • Study site: George Washington Medical Faculty Associates, Washington, DC
  • Number of participants: up to 30 in 3 cohorts of 10 volunteers each

In Cohort 1, ten (10) volunteers will receive an inoculum of 25 infectious Necator americanus larvae. In Cohort 2, ten (10) volunteers will receive an inoculum of 50 infectious Necator americanus larvae. In the optional Cohort 3, ten (10) volunteers will receive an inoculum of 75 infectious Necator americanus larvae.

The cohorts will be enrolled in a staggered fashion with safety data assessed prior to larval dose escalation. Cohort 2 will be inoculated no earlier than 8 weeks after the last volunteer is inoculated in Cohort 1. The optional Cohort 3 will be inoculated no sooner than 8 weeks after the last volunteer is inoculated in Cohort 2. Cohort 3 will be enrolled only if the tolerability of the experimental infection of Cohort 2 is acceptable and does not result in significant adverse events.

Within each cohort, after Study Day 70, but before Study Day 77, up to 5 volunteers will undergo capsule endoscopy in order to visualize and count adult N. americanus hookworms residing in the intestine. Informed consent for capsule endoscopy will be obtained separately from the primary study, and agreement or refusal will not impact on a subject's eligibility to enroll or continue participation in the primary study.

Three months after larval administration, or at the time of study withdrawal, all participants will receive a 3-dose treatment of albendazole (400 mg per dose) for clearance of experimental infection.

  • Larval inoculum schedule: Study Day 0 (single application)
  • Route: applied to intact skin on the volar aspect of forearm
  • Doses of N. americanus Larval Inoculum to be tested: 25, 50 and 75 infectious larvae (high dose optional)
  • Study duration: 6 months per study participant; total duration of the study estimated at approximately 13 months
  • Anthelmintic treatment: 3 months post larval inoculum, or at study withdrawal, 3-dose treatment with 400 mg albendazole
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: An Experimental Infection Study of Dermally-applied Infectious Necator Americanus Hookworm Larvae in Hookworm-naïve Adults
Actual Study Start Date : January 2015
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 25 Necator americanus Hookworm Larvae Biological: Necator americanus Hookworm Larvae
Infectious larvae of the human hookworm Necator americanus
Other Name: Na-L3
Experimental: 50 Necator americanus Hookworm Larvae Biological: Necator americanus Hookworm Larvae
Infectious larvae of the human hookworm Necator americanus
Other Name: Na-L3
Experimental: 75 Necator americanus Hookworm Larvae Biological: Necator americanus Hookworm Larvae
Infectious larvae of the human hookworm Necator americanus
Other Name: Na-L3


Outcome Measures
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Primary Outcome Measures :
  1. Study product-related adverse events [ Time Frame: Up to 6 months after dosing ]
    Frequency of study product-related adverse events, graded by severity, for different doses of N. americanus Larval Inoculum.


Secondary Outcome Measures :
  1. Fecal egg counts [ Time Frame: Up to Study Day 101 ]
    To determine the dose of N. americanus Larval Inoculum that generates the highest fecal egg counts, measured by fecal microscopy.

  2. Number of adult hookworms in feces post-treatment [ Time Frame: Study Days 87-101 ]
    To compare the N. americanus Larval Inoculum dose received with the number of adult worms present in the gut, as determined by capsule endoscopy.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Males or females between 18 and 45 years, inclusive.
  • Good general health as determined by means of the screening procedure.
  • Available for the duration of the trial (6 months).
  • Willingness to participate in the study as evidenced by signing the informed consent document.

Exclusion Criteria:

  • Pregnancy as determined by a positive urine human choriogonadotropin (hCG) (if female).
  • Participant unwilling to use reliable contraception methods while participating in the study (if female and not surgically sterile, abstinent or at least 2 years post-menopausal).
  • Currently lactating and breast-feeding (if female).
  • Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies.
  • Known or suspected immunodeficiency.
  • Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25-times the upper reference limit).
  • Laboratory evidence of renal disease (serum creatinine greater than 1.25-times the upper reference limit, or more than trace protein or blood on urine dipstick testing).
  • Laboratory evidence of hematologic disease (hemoglobin <11.5 g/dl [females] or <12.5 g/dl [males]; absolute leukocyte count <3.6 or >10.7 x 103/mm3; absolute neutrophil count [ANC] <1.7 x 103/mm3; absolute lymphocyte count <0.7 x 103/mm3; or platelet count <140 x 103/mm3).
  • History of iron deficiency anemia.
  • History of hypoalbuminemia.
  • Laboratory evidence of a coagulopathy (PTT or PT INR greater than 1.1-times the upper reference limit).
  • Serum glucose (random) greater than 1.2-times the upper reference limit.
  • 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.
  • 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.
  • Severe asthma as defined by the need for daily use of inhalers or emergency clinic visit or hospitalization within 6 months of the volunteer's expected Day 0 of the study.
  • Positive ELISA for hepatitis B surface antigen (HBsAg).
  • Positive confirmatory test for HIV infection.
  • Positive confirmatory test for hepatitis C virus (HCV) infection.
  • Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of the volunteer's expected Day 0 of this study or planned use during the study.
  • Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to the volunteer's expected Day 0 of the study.
  • Receipt of blood products within the past 6 months.
  • Known allergy to amphotericin B or gentamicin.
  • History of previous infection with hookworm or residence for more than 6 months in a hookworm-endemic area.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01940757


Contacts
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Contact: Hanna-Grace Rabanes (202) 994-1599 gwvru@gwu.edu

Locations
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United States, District of Columbia
George Washington University Medical Faculty Associates Recruiting
Washington, District of Columbia, United States, 20037
Contact: Caroline Thoreson, PA    202-741-2443    gwvru@gwu.edu   
Sub-Investigator: Aimee Desrosiers, PA         
Sub-Investigator: Elissa Malkin, DO, MPH         
Sub-Investigator: Caroline Thoreson, PA         
Sponsors and Collaborators
Baylor College of Medicine
Investigators
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Principal Investigator: David J Diemert, MD George Washington University
  Study Documents (Full-Text)

Documents provided by Maria Elena Bottazzi PhD, Baylor College of Medicine:
Informed Consent Form  [PDF] November 18, 2019

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Maria Elena Bottazzi PhD, Sponsor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01940757    
Other Study ID Numbers: SVI-CH-01
First Posted: September 12, 2013    Key Record Dates
Last Update Posted: January 10, 2023
Last Verified: January 2023
Keywords provided by Maria Elena Bottazzi PhD, Baylor College of Medicine:
Necator americanus
Hookworm Infection
Experimental challenge infection
Additional relevant MeSH terms:
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Infections
Communicable Diseases
Hookworm Infections
Ancylostomiasis
Disease Attributes
Pathologic Processes
 Strongylida Infections
Secernentea Infections
Nematode Infections
Helminthiasis
Parasitic Diseases