Trial no.:	PACTR202202553002020	Date of Registration:	18/02/2022
Trial Status:	Registered in accordance with WHO and ICMJE standards

TRIAL DESCRIPTION

Public title

Expanding research capacities at CERMEL to accelerate the control/elimination of Hookworm infection.

Official scientific title

Necator americanus infection in participants living in sub- Saharan Africa: a randomized, controlled phase 1 clinical trial in healthy adults living in Lambaréné, Gabon

Brief summary describing the background and objectives of the trial

With around 230 million people infected worldwide, hookworm is one of the most common and the most important parasitic infection of humans. High hookworm burden predominantly affects the poor and may cause iron-deficiency anaemia, hypoalbuminaemia, impaired cognitive development, and undernutrition. Unfortunately, mass drug administration, the cornerstone of hookworm control programmes, is threatened by increasing drug failure and high reinfection rates. Novel/improved anthelminthic drugs and vaccines are needed to add to the hookworm control tools. Expanding scientific capacities of research institutions working in endemic regions is essential to the acceleration of identification of mechanisms and patterns that will aid the development of new drugs and vaccines. A controlled human hookworm infection (CHHI) model would accelerate the development of novel vaccines and drugs for hookworm infection. We now intend to establish a CHHI model here in Gabon to look at possible biological and immunological parameter changes that are exclusive to the SSA region. These changes might account for varying efficacies of vaccines and drugs within the region in comparison to the West. The development of a CHHI model in Africa would also allow for vaccine development and drug development within the continent.

Type of trial

RCT

Acronym (If the trial has an acronym then please provide)

CHHIA

Disease(s) or condition(s) being studied

Infections and Infestations

Sub-Disease(s) or condition(s) being studied

Hookworm Disease

Purpose of the trial

Controlled Human Infection

Anticipated trial start date

01/04/2022

Actual trial start date

Anticipated date of last follow up

31/12/2022

Actual Last follow-up date

Anticipated target sample size (number of participants)

15

Actual target sample size (number of participants)

Recruitment status

Not yet recruiting

Publication URL

Secondary Ids	Issuing authority/Trial register

STUDY DESIGN
Intervention assignment	Allocation to intervention	If randomised, describe how the allocation sequence was generated	Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms	Masking	If masking / blinding was used
Parallel: different groups receive different interventions at same time during study	Randomised	Simple randomization using a randomization table created by a computer software program	Allocation was determined by the holder of the sequence who is situated off site	Masking/blinding used	Care giver/Provider,Outcome Assessors,Participants

INTERVENTIONS
Intervention type	Intervention name	Dose	Duration	Intervention description	Group size	Nature of control
Experimental Group	Necator americanus L3 larvae	50	16 weeks	Dermal exposure to 50 N. americanus L3 larvae suspended in sterile water, which will be applied to the volar sides of both forearms and dorsal aspects of both calves of the study volunteer and fixed with a transparent adhesive tape for one hour.	10
Control Group	Sterile water	0.5ml	1 hour	Sterile water will be divided over four sterile absorbent pads, which will be applied to the volar sides of both forearms and dorsal aspects of both calves of the study volunteer and fixed with a transparent adhesive tape for one hour.	5	Placebo

ELIGIBILITY CRITERIA
List inclusion criteria	List exclusion criteria	Age Category	Minimum age	Maximum age	Gender
1. Subject is aged ≥ 21 and ≤ 45 years. 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. Subjects are able to respond to phone calls within 24 hours during the first 16 weeks of the study. 5. Subject is willing to refrain from blood donation procedures throughout the study period. 6. Subject has signed informed consent. 7. Subject is negative for helminth infections: PCR negative for hookworm and Strogyloides stercoralis; Negative for Ascaris lumbricoides, Trichuris trichuria, and Schistosoma spp by microscopy. Negative for Loa Loa by microscopy and blood concentration. 8. Subject is willing to remain in the study area throughout the trial period.	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, hematological, 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: history of severe asthma or other health conditions that may require future steroid use; body weight <50 kg or 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 Hb value <7 g/dl; 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; inflammatory 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 type 1 hypersensitivity to amphotericin B or gentamicin. 4. Positive fecal PCR or Kato-Katz for hookworm at screening. 5. Current or past scars, tattoos.	Adult: 18 Year(s)-44 Year(s)	21 Year(s)	45 Year(s)	Male

ETHICS APPROVAL

Has the study received appropriate ethics committee approval

Date the study will be submitted for approval

Date of approval

Name of the ethics committee

Yes

15/10/2021

Gabonese National Ethics Committee

Ethics Committee Address
Street address	City	Postal code	Country
Libreville	Libreville	B.P. 2217	Gabon

OUTCOMES
Type of outcome	Outcome	Timepoint(s) at which outcome measured
Primary Outcome	1. Frequency and intensity of adverse events following single exposure to hookworm larvae 2. Detection of hookworm eggs by faeces microscopy (Kato-Katz) at any week between week 9 to 16 post-infection. 3. Humoral (antibody) and cellular immunological changes after controlled hookworm human infection. 4. Time to positive faeces test for hookworm as defined by Kato-Katz and PCR	Baseline, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks
Secondary Outcome	1. Rates, subtypes and functions of antibodies after controlled human hookworm infection. 2. Innate and adaptive cell frequencies after controlled human hookworm infection. 3. Molecular mapping of Necator americanus Lambaréné strain.	Baseline, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks

RECRUITMENT CENTRES
Name of recruitment centre	Street address	City	Postal code	Country
CERMEL	N/A	Libreville	BP 242	Gabon

FUNDING SOURCES
Name of source	Street address	City	Postal code	Country
CERMEL	Libreville	Libreville	B.P. 242	Gabon

SPONSORS
Sponsor level	Name	Street address	City	Postal code	Country	Nature of sponsor
Primary Sponsor	CERMEL	Libreville	Libreville	B.P. 242	Gabon	Nonprofit Organization

COLLABORATORS
Name	Street address	City	Postal code	Country
Leiden University Medical Center Department of Parasitology	Albinusdreef 2	Leiden	9600	Netherlands

CONTACT PEOPLE
Role	Name	Email	Phone	Street address
Principal Investigator	Selidji Agnandji	agnandjis@cermel.org	+24177989191	Libreville
City	Postal code	Country	Position/Affiliation
Libreville	B.P. 242	Gabon	Director
Role	Name	Email	Phone	Street address
Public Enquiries	Ayodele Alabi	ayodele.alabi@cermel.org	+24177989191	Libreville
City	Postal code	Country	Position/Affiliation
Libreville	B.P. 242	Gabon	Clinical Investigator
Role	Name	Email	Phone	Street address
Scientific Enquiries	Ayodele Alabi	ayodele.alabi@cermel.org	+24177989191	Libreville
City	Postal code	Country	Position/Affiliation
Libreville	B.P. 242	Gabon	Clinical Investigator
Role	Name	Email	Phone	Street address
Public Enquiries	Selidji Agnandji	agnandjis@cermel.org	+241077989191	Libreville
City	Postal code	Country	Position/Affiliation
Libreville		Gabon	Director of CERMEL
Role	Name	Email	Phone	Street address
Scientific Enquiries	Selidji Agnandji	agnandjis@cermel.org	+24177989191	Libreville
City	Postal code	Country	Position/Affiliation
Libreville		Gabon	Director of CERMEL

REPORTING
Share IPD	Description	Additional Document Types	Sharing Time Frame	Key Access Criteria
Yes	Upon completion of data entry and cleaning, clinical and laboratory data will be anonymised and deposited in CERMEL data repository.	Study Protocol	Data will be available for 5 years	Data will be made available upon reasonable request after the publication of the trial results.
URL	Results Available	Results Summary	Result Posting Date	First Journal Publication Date
	No
Result Upload 1:	Result Upload 2:	Result Upload 3:	Result Upload 4:	Result Upload 5:

Result URL Hyperlinks	Link To Protocol
Result URL Hyperlinks

Changes to trial information

Pan African Clinical Trials Registry