ReCHHI1: Repeated Controlled Human Hookworm Infection

Sponsor

Meta Roestenberg (Other)

Overall Status

Completed

CT.gov ID

NCT03257072

Collaborator

(none)

Enrollment

Location

Arms

7.6

Actual Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Necator Americanus Infection	Biological: 50 Necator americanus L3 larvae Biological: 100 Necator americanus L3 larvae Biological: 150 Necator americanus L3 larvae	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

double-blind, placebo-controlled, dose-escalation trialdouble-blind, placebo-controlled, dose-escalation trial

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

double-blind

Primary Purpose:

Diagnostic

Official Title:

Repeated Controlled Human Hookworm Infection in Healthy Dutch Volunteers

Actual Study Start Date :

Jan 10, 2018

Actual Primary Completion Date :

Aug 30, 2018

Actual Study Completion Date :

Aug 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A: 50 Necator americanus L3 larvae Mock infections with water at week 0 and 2, infection with 50 Necator americanus L3 larvae at week 4	Biological: 50 Necator americanus L3 larvae 1x50 Necator americanus L3 larvae
Experimental: B: 100 Necator americanus L3 larvae Mock infections with water at week 0, infection with 50 Necator americanus L3 larvae at week 2 and 4	Biological: 100 Necator americanus L3 larvae 2x50 Necator americanus L3 larvae
Experimental: C: 150 Necator americanus L3 larvae Infection with 50 Necator americanus L3 larvae at week 0, 2 and 4	Biological: 150 Necator americanus L3 larvae 3x50 Necator americanus L3 larvae

Arm

Intervention/Treatment

Experimental: A: 50 Necator americanus L3 larvae

Mock infections with water at week 0 and 2, infection with 50 Necator americanus L3 larvae at week 4

Biological: 50 Necator americanus L3 larvae

1x50 Necator americanus L3 larvae

Experimental: B: 100 Necator americanus L3 larvae

Mock infections with water at week 0, infection with 50 Necator americanus L3 larvae at week 2 and 4

Biological: 100 Necator americanus L3 larvae

2x50 Necator americanus L3 larvae

Experimental: C: 150 Necator americanus L3 larvae

Infection with 50 Necator americanus L3 larvae at week 0, 2 and 4

Biological: 150 Necator americanus L3 larvae

3x50 Necator americanus L3 larvae

Outcome Measures

Primary Outcome Measures

Frequency of adverse events [28 weeks]
Frequency of adverse events as compared between study groups A, B and C.
Magnitude of adverse events [28 weeks]
Magnitude of adverse events as compared between study groups A, B and C.

Secondary Outcome Measures

Variability in egg secretion [20 weeks]
Variability in egg secretion by Kato-Katz from week 16 to 20
Lowest dose at which there is 100% patent hookworm infection [20 weeks]
The lowest dose at which there is 100% patent hookworm infection, as defined by a positive Kato-Katz at any time between week 16 to 20
Comparison of the average number of eggs secreted [20 weeks]
Comparison of the average number of eggs secreted by Kato-Katz and qPCR between different groups in weeks 16-20 after the infection

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion 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, 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 has signed informed consent.

Exclusion Criteria:

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.

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 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
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
Subjects with planned travel to hookworm endemic areas during this trial
Receipt of a vaccine within 4 weeks prior to the study initiation
Known food allergy