Development of AWZ1066S, a Small Molecule Anti-Wolbachia Candidate Macrofilaricide Drug

Summary

Lymphatic filariasis and onchocerciasis are a group of neglected tropical diseases caused by the transmission of worm larvae (microfilaria) by biting insects. Once a human is infected, the larvae mature into adult worms that release huge numbers of larvae into the lymphatics for 5-15 years. The larvae cause tissue damage resulting in the disabling diseases of elephantiasis (gross leg and scrotal swelling) and river blindness. These diseases affect 160 million people and are acknowledged major public health problems in the tropics. Current treatments mainly target the larvae but not the adult worms that live for years, meaning that repeated courses of treatment over many years are needed. These repeated courses are usually delivered at population level in the form of mass drug administration programmes.

For the adult worms to be able to grow, reproduce and infect more humans they are dependent on a bacterium which lives inside them. This bacterium (Wolbachia) is not naturally found in humans. Some drugs are able to target Wolbachia, however they are unsuitable for mass drug administration programmes because they have to be given for 4-6 weeks and cannot be used in children or pregnant women.

AWZ1066S is a novel drug developed in Liverpool that has been shown in experimental models to target Wolbachia and indirectly kill the adult parasitic worms after a 7 day course. After extensive safety testing in animals we are conducting a Phase 1, first in human study, to assess the safety, tolerability and pharmacokinetics of ascending single and multiple oral doses of AWZ1066S in healthy volunteers. The study is a single centre study, will last approximately 1 year and will take place in a dedicated Phase 1 trial unit. Depending on which group they are enrolled into, participants will take either one dose, two doses or seven doses and their involvement will last between 38 and 45 days. Participants will be closely monitored for adverse effects.

Conditions

• Filariasis, Lymphatic
• Onchocerciasis

Interventions

DRUG

AWZ1066S

Candidate drug to treat lymphatic filariasis by targeting Wolbachia endosymbiont

DRUG

Placebo

Placebo

Sponsors & Collaborators

• Liverpool University Hospitals NHS Foundation Trust

  collaborator OTHER_GOV

• Covance

  collaborator INDUSTRY

• Subiaco Associates Limited

  collaborator UNKNOWN

• Sylexis Limited

  collaborator UNKNOWN

• Eisai Limited

  collaborator INDUSTRY

• Liverpool School of Tropical Medicine

  lead OTHER

Principal Investigators

• Graham Devereux, MD · Liverpool School of Tropical Medicine

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-12-10

Primary Completion

2023-05-22

Completion

2023-05-22

Countries

• United Kingdom

Study Locations