Clinical trial NCT03257072: Repeated Controlled Human Hookworm Infection
Official title: Repeated Controlled Human Hookworm Infection in Healthy Dutch Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Necator Americanus Infection
Keywords: hookworm
controlled human infection model
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2017-08-22
Enrollment: 24
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: double-blind, placebo-controlled, dose-escalation trial
Primary purpose: DIAGNOSTIC

Brief summary: Twenty-four healthy hookworm-naive volunteers will be exposed to 50 L3 Necator americanus larvae for a maximum of three times.

Detailed description: Twenty-four volunteers will be allocated equally into three groups (i.e. group A, B, C). Group A, B, and C will have one, two, and three infections respectively. Every infection will be performed with 50 L3 Necator americanus larvae. Group A will receive infection at week 4 only. Group B will be infected at week 2 and week 4. Group C will be infected at week 0, 2 and 4. To maintain blinding, group A and B will receive mock infections with water at week 0 and week 0 and 2 respectively. The interval between each CHHI is 2 weeks. Before every infection, the safety will be assessed by a review of adverse events data with a local safety monitor.

Sixteen weeks after the last infection (week 20), all volunteers will be offered treatment with a 3-day regimen of albendazole to abrogate infection. Volunteers with average egg counts \>250 eggs per gram will be asked if they would be willing to keep their infection for a maximum of two years (chronic donors). No more than four volunteers will be selected to be chronic donors. Six months after the last infection (or after the last donation for the chronic donors) volunteers will undergo their last visit.

Eligibility criteria: Inclusion 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, 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 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:

   * Body Mass Index (BMI) \<18.0 or \>30.0 kg/m2 at screening;
   * 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 \<7.0 mmol/L for females or \<8.0 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.
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 or Kato-Katz for hookworm at screening, any known history of hookworm infection or treatment for hookworm infection or possible exposure to hookworm in the past
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
8. Subjects with planned travel to hookworm endemic areas during this trial
9. Receipt of a vaccine within 4 weeks prior to the study initiation
10. Known food allergy

Primary outcomes:
measure: Frequency of adverse events
timeFrame: 28 weeks
measure: Magnitude of adverse events
timeFrame: 28 weeks
Secondary outcomes:
measure: Variability in egg secretion
timeFrame: 20 weeks
measure: Lowest dose at which there is 100% patent hookworm infection
timeFrame: 20 weeks
measure: Comparison of the average number of eggs secreted
timeFrame: 20 weeks
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
affiliation: LUMC
name: Meta Roestenberg, MD. PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoogerwerf MA, Koopman JPR, Janse JJ, Langenberg MCC, van Schuijlenburg R, Kruize YCM, Brienen EAT, Manurung MD, Verbeek-Menken P, van der Beek MT, Westra IM, Meij P, Visser LG, van Lieshout L, de Vlas SJ, Yazdanbakhsh M, Coffeng LE, Roestenberg M. A Randomized Controlled Trial to Investigate Safety and Variability of Egg Excretion After Repeated Controlled Human Hookworm Infection. J Infect Dis. 2021 Mar 3;223(5):905-913. doi: 10.1093/infdis/jiaa414.