Clinical trial NCT03702530: Immunisation, Treatment and Controlled Human Hookworm Infection
Official title: Immunisation, Treatment and Controlled Human Hookworm Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Necator Americanus Infection
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2018-10-11
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Volunteers are randomized into either the intervention or the placebo group (2:1 allocation). The two groups run parallel in the trial. At the moments of immunization in the intervention group volunteers in the placebo group receive a mock infection with water to maintain blinding.
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Difference between egg counts between intervention and placebo group
timeFrame: week 25-29
Secondary outcomes:
measure: Frequency of adverse events
timeFrame: week 0-29
measure: Severity of adverse events
timeFrame: week 0-29
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
affiliation: Leiden University Medical Center
name: M. Roestenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: