Immunisation, Treatment and Controlled Human Hookworm Infection

NCT ID: NCT03702530

Last Updated: 2019-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-17
• Study Completion Date: 2019-09-02

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.

Conditions

Necator Americanus Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Intervention

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

Group Type: EXPERIMENTAL

3x 50 L3 larvae immunisation with albendazole treatment

Intervention Type: BIOLOGICAL

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

2x 50 L3 larvae infection

Intervention Type: BIOLOGICAL

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

Placebo

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

Group Type: PLACEBO_COMPARATOR

3x placebo immunisation with albendazole treatment

Intervention Type: OTHER

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

2x 50 L3 larvae infection

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

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

Intervention Type: OTHER

2x 50 L3 larvae infection

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

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Meta Roestenberg

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

M. Roestenberg, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

Leiden University Medical Center

Leiden, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 38042152 (View on PubMed)

Other Identifiers

ITCHHI

Identifier Type: -

Identifier Source: org_study_id