None listed
Conditions
Brief summary
This is a stage 1b placebo controlled clinical trial investigating the safety and tolerability of an attenuated live hookworm vaccine. The study will be performed in two parts. Stage 1. The degree to which attenuation will impede the larvae’s ability to penetrate the skin in vivo is unknown. This is a dose escalation stage performed to de ne the optimal dose to be used in stage 2. The dose in cohort 1 will be 50 attenuated larvae dermaly applied to the volar aspect of the forearm, approximately 4 inches proximal to the thumb. Dose escalation will occur after safety review following completion of cohort 1. Cohort 2 will consist of 100 attenuated hookworm larvae applied in the same way. The optimal dose is defined as the number of larvae required to produce a grade 2 -3 dermal reaction. Cohorts of two participants will be enrolled and inoculated sequentially with attenuated hookworm. Safety and tolerability data will be collected and used to guide the escalation of dose for use in the next cohort. STAGE 2 Pilot randomised control trial 15 participants will be randomly assigned 1:2 to receive either 2 doses of placebo or attenuated larvae via dermal application 6 weeks apart. Albendazole will be administered 4 weeks following each inoculation. 6 weeks following the second dose all participants will receive a challenge dose of 30 normal hookworm larvae (15 larvae dermaly applied to each forearm). Albendazole 400mg (200mg tablets, Zentel – Glaxo-Smith-Kline) will be administered at the termination of the studyat week 11. Outcomes measured will include adverse events, faecal hookworm egg content and immune response
Interventions
Stage 1
A dose escalation study to define the dose of attenuated larvae for use in stage 2. Optimal dose defined as the number of larvae required to produce a grade 2-3 dermal reaction. Cohorts of 2 participants will be enrolled and receive a single inoculation with attenuated larvae and placebo (Tobasco sauce), via dermal application to the volar aspect of each forearm. Inoculation of participants will be sequential, with safety review (at day 3 post inoculation) before inoculation of the
Stage 1 A dose escalation study to define the dose of attenuated larvae for use in stage 2. Optimal dose defined as the number of larvae required to produce a grade 2-3 dermal reaction. Cohorts of 2 participants will be enrolled and receive a single inoculation with attenuated larvae and placebo (Tobasco sauce), via dermal application to the volar aspect of each forearm. Inoculation of participants will be sequential, with safety review (at day 3 post inoculation) before inoculation of the second participant. Cohorts will be enrolled until the desired dermal reaction is produced with safety review before dose escalation. Cohort 1 and 2 will use 50 and 100 attenuated larvae respectively. Doses for use in future cohorts will be defined by the safety review team. 28 days following inoculation all participants will receive Albendazole (2 x 200mg tablets, PO on empty stomach). If a participant has no dermal reaction (implying no penetrating larvae) the participant may be enrolled in future cohorts. Once a participant has experienced a dermal reaction they are excluded from further participation. Stage 2 This is a randomised controlled trial comparing vaccination to placebo in protecting against a challenge infection with normal hookworm larvae. Participants will be randomised 1:2 to receive either 2 doses of placebo (Tobasco sauce) or attenuated hookworm vaccine (dose defined in stage 1) via dermal application to the volar aspect of the forearm, 6 weeks apart. All participants will receive Albendazole 400mg (2 x 200mg tablets, PO on empty stomach) 4 weeks following both inoculations. 6 weeks following the second inoculation all participants will receive a challenge dose of 30 normal hookworm larvae by dermal application (15 larvae to each forearm). All participants will be administered Albendazole (2 x 200mg tablets, PO on empty stomach) at the termination of the study (week 11 of stage 2).
Sponsors
QIMR Berghofer Medical Research Institute
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Participants will be males and non-pregnant, non-lactating females aged between 18 and 65 years. Participants must have BMI within the range of 18-35 kg/m2 and weigh more than 50 kg. Participants must understand the procedures involved and agree to participate in the study by giving fully informed, written consent prior to any study assessment. Participants must be contactable and available for the duration of the clinical trial and be available for up to 2 months following completion of the trial. Female volunteers of childbearing potential, should be irreversibly surgically sterile (tubal ligation) with or without hysterectomy at least 6 months ago or be using injectable, insertable, transdermal or combination oral contraceptive approved by the Therapeutic Goods Administration (TGA) combined with barrier contraception (female condom or male partners to use condom) through completion of the study and have negative urinary pregnancy tests prior to albendazole use. Menopausal participants (confirmed by follicle-stimulating hormone [FSH]) do not require contraception.
Exclusion criteria
History of Helminth infection (other than E. vermicularis) or travel to and residence (greater than 2 weeks) in areas of endemic transmission of these parasites. History of atopy or severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion. History of allergic reaction, anaphylaxis or otherwise to iodine, amphotericin, albendazole, chilli or other peppers, or Tabasco sauce. Treatment with immune-modulating medications in the last 6 months. Current iron deficiency anaemia. Any vaccination in the last 30 days. Heavily tattooed forearms
Outcome results
None listed