Immunisation, Treatment and Controlled Human Hookworm Infection

NCT03702530 | Completed DMC

• 1 other identifier: ITCHHI
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Necator Americanus Infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Frequency of adverse events

  week 0-29

• Severity of adverse events

  week 0-29

Study Arms (2)

Intervention

EXPERIMENTAL

3x 50 L3 larvae immunisation with albendazole treatment and 2x 50 L3 larvae infection

Biological: 3x 50 L3 larvae immunisation with albendazole treatment; Biological: 2x 50 L3 larvae infection

Placebo

PLACEBO COMPARATOR

3x placebo immunisation with albendazole treatment and 2x 50 L3 larvae infection

Other: 3x placebo immunisation with albendazole treatment; Biological: 2x 50 L3 larvae infection

Interventions

3x 50 L3 larvae immunisation with albendazole treatment BIOLOGICAL

Immunisation with 50 Necator americanus L3 larvae at week 0, 3 and 6 with albendazole treatment at week 2, 5 and 8

Intervention

3x placebo immunisation with albendazole treatment OTHER

Mock immunisation with water at week 0, 3 and 6 with albendazole treatment at week 2, 5 and 8

Placebo

2x 50 L3 larvae infection BIOLOGICAL

After (mock) immunisation, infection with 50 Necator americanus larvae at week 13 and 15

Intervention; Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Subject is aged ≥ 18 and ≤ 45 years and in good health.
• Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
• Subject is able to communicate well with the investigator and is available to attend all study visits.
• Subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period.
• For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.
• Subject agrees to refrain from travel to a hookworm endemic area during the course of the trial.
• Subject has signed informed consent.

You may not qualify if:

• 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.
• 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).
• Known allergy to amphotericin B or gentamicin.
• For female subjects: positive urine pregnancy test at screening.
• Positive faecal qPCR for hookworm at screening, any known history of hookworm infection or treatment for hookworm infection.
• Being an employee or student of the department of Parasitology of the LUMC.
• Current or past scars, tattoos, or other disruptions of skin integrity at the intended site of larval application.

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

Related Publications (1)

• Hoogerwerf MA, Janse JJ, Kuiper VP, van Schuijlenburg R, Kruize YC, Sijtsma JC, Nosoh BA, Koopman JR, Verbeek-Menken PH, Westra IM, Meij P, Brienen EA, Visser LG, van Lieshout L, Jochems SP, Yazdanbakhsh M, Roestenberg M. Protective efficacy of short-term infection with Necator americanus hookworm larvae in healthy volunteers in the Netherlands: a single-centre, placebo-controlled, randomised, controlled, phase 1 trial. Lancet Microbe. 2023 Dec;4(12):e1024-e1034. doi: 10.1016/S2666-5247(23)00218-5.

  PMID: 38042152 DERIVED

Study Officials

• M. Roestenberg, MD, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participant, clinical trial physicians and laboratory personnel are blinded for treatment allocation. Blinding is maintained by exposing the volunteers in the placebo group to a mock infection with water. During the trial clinical trial physicians are blinded to the outcome measures (i.e. Kato-Katz outcomes), laboratory staff are blinded for the study code of samples delivered.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: August 10, 2018
• First Posted: October 11, 2018
• Study Start: December 17, 2018
• Primary Completion: September 2, 2019
• Study Completion: September 2, 2019
• Last Updated: September 4, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)