Immunisation, Treatment and Controlled Human Hookworm Infection (ITCHHI)

24 healthy volunteers will be immunized with three times 50 L3 larvae or placebo followed by treatment with albendazol and subsequently challenged with twice 50 L3 larvae.

Study Overview

• Status: Completed
• Conditions: Necator Americanus Infection
• Intervention / Treatment: Biological: 3x 50 L3 larvae immunisation with albendazole treatment; Biological: 2x 50 L3 larvae infection; Other: 3x placebo immunisation with albendazole treatment

Detailed Description

24 healthy hookworm-naive volunteers will be randomized in a 2:1 allocation to either the intervention group or placebo. Volunteers in the intervention group will be immunized three times with 50 L3 larvae of Necator americanus with three-week intervals. Two weeks after each immunization, volunteers will be treated with albendazole. Four weeks after the last treatment all volunteers are challenged with controlled human hookworm infection consisting of two doses of 50 L3 larvae with a two week interval. 16 weeks after the first challenge all volunteers will be treated with albendazole, except up to four volunteers who will be asked to remain as chronic donors for future hookworm studies.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

1. Subject is aged ≥ 18 and ≤ 45 years and in good health.
2. Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
3. Subject is able to communicate well with the investigator and is available to attend all study visits.
4. Subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period.
5. For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.
6. Subject agrees to refrain from travel to a hookworm endemic area during the course of the trial.
7. Subject has signed informed consent.

Exclusion Criteria:

1. Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immune-deficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following:

   • positive HIV, HBV or HCV screening tests;
   • the use of immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period;
   • having one of the following laboratory abnormalities: ferritine <10 ug/L, transferrine <2.04 g/L or Hb <6.5 mmol/L for females or <7.5 mmol/L for males.
   • history of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years;
   • any history of treatment for severe psychiatric disease by a psychiatrist in the past year;
   • history of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset;
   • inflammmatory bowel syndrome;
   • regular constipation, resulting in bowel movements less than three times per week.
2. Known hypersensitivity to or contra-indications for use of albendazole, including co-medication known to interact with albendazole metabolism (e.g. carbamazepine, phenobarbital, phenytoin, cimetidine, theophylline, dexamethasone).
3. Known allergy to amphotericin B or gentamicin.
4. For female subjects: positive urine pregnancy test at screening.
5. Positive faecal qPCR for hookworm at screening, any known history of hookworm infection or treatment for hookworm infection.
6. Being an employee or student of the department of Parasitology of the LUMC.
7. Current or past scars, tattoos, or other disruptions of skin integrity at the intended site of larval application.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intervention; 3x 50 L3 larvae immunisation with albendazole treatment and 2x 50 L3 larvae infection	Biological: 3x 50 L3 larvae immunisation with albendazole treatment; Immunisation with 50 Necator americanus L3 larvae at week 0, 3 and 6 with albendazole treatment at week 2, 5 and 8; Biological: 2x 50 L3 larvae infection; After (mock) immunisation, infection with 50 Necator americanus larvae at week 13 and 15
PLACEBO_COMPARATOR: Placebo; 3x placebo immunisation with albendazole treatment and 2x 50 L3 larvae infection	Biological: 2x 50 L3 larvae infection; After (mock) immunisation, infection with 50 Necator americanus larvae at week 13 and 15; Other: 3x placebo immunisation with albendazole treatment; Mock immunisation with water at week 0, 3 and 6 with albendazole treatment at week 2, 5 and 8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between egg counts between intervention and placebo group	Comparison of average egg counts from week 25-29 of the trial (which is week 12 to 16 after controlled human hookworm infection) by Kato-Katz between intervention group and placebo group	week 25-29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse events	Comparison of frequency of adverse events collected during immunisation phase and after controlled human hookworm infection between intervention and placebo group	week 0-29
Severity of adverse events	Comparison of severity of adverse events collected during immunisation phase and after controlled human hookworm infection between intervention and placebo group	week 0-29

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Investigators: Principal Investigator: M. Roestenberg, MD, PhD, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 17, 2018
• Primary Completion (ACTUAL): September 2, 2019
• Study Completion (ACTUAL): September 2, 2019

Study Registration Dates

• First Submitted: August 10, 2018
• First Submitted That Met QC Criteria: October 8, 2018
• First Posted (ACTUAL): October 11, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 4, 2019
• Last Update Submitted That Met QC Criteria: September 2, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Parasitic Diseases; Secernentea Infections; Nematode Infections; Helminthiasis; Strongylida Infections; Infections; Communicable Diseases; Hookworm Infections; Ancylostomiasis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiprotozoal Agents; Antiparasitic Agents; Anthelmintics; Antiplatyhelmintic Agents; Anticestodal Agents; Albendazole
• Other Study ID Numbers: ITCHHI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No