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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: An Experimental Infection Study of Dermally-applied Infectious Necator Americanus Hookworm Larvae in Hookworm-naïve Adults

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.

Detailed Summary:

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
Sponsor: Baylor College of Medicine

Current Primary Outcome: 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.
  • 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.


Original Secondary Outcome: Same as current

Information By: Baylor College of Medicine

Dates:
Date Received: September 9, 2013
Date Started: January 2015
Date Completion: December 2017
Last Updated: May 30, 2017
Last Verified: May 2017