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Malaria Challenge Model

Advancing of novel antimalarial drug and vaccine candidates

The Challenge

Malaria is a serious and life-threatening, mosquito borne disease prevalent across much of tropical and sub-tropical Asia, South America and Sub-Saharan Africa. Due to increasing resistance to current antimalarial regimens, new drugs are required as both stand-alone and partner therapies to address a growing medical need. New therapies will not only reduce mortality and disease in vulnerable populations, but also to help the move towards a greater goal of malaria elimination. Malaria is classified as an unmet need in healthcare. In 2015 the World Health Assembly endorsed aims to reduce malaria burden by 90% by 2030.

hVIVO is developing further capability and capacity in its unique Human Challenge facilities to assist in the advancement of novel antimalarial drug and vaccine candidates and is now able to offer a Direct Venous Inoculation (DVI), Controlled Human Malaria Infection (CHMI) model for estimations of efficacy. Results from CHMI modelling of drug and vaccine efficacy have shown good translation into the field.

Validated Malaria Model

Reproducibility: Sanaria PfSPZ Challenge has been used in multiple clinical trials in the United Kingdom, United States, Europe, Australia and Africa.

Standardisation: A GMP manufactured P. falciparum sporozoite challenge agent (Sanaria PfSPZ Challenge)

Reproducibility: Sanaria PfSPZ Challenge Experience: As of June 2021, 1,204 volunteers have received 2,011 doses of Sanaria PfSPZ Challenge (NF54) with no deaths, unresolved significant adverse events, or sequelae to date. hVIVO successfully completed a familiarisation study in 2022 – results to be presented at the British Society of Parasitology in March.

Safety: Documented symptoms are mostly mild to moderate and include headache, fever, nausea and fatigue.

Vaccine Trials

Conceptual Challenges:

Demonstrating efficacy of novel malaria vaccines in the field is time-consuming, costly and associated with risk

  • Exposure to the malarial parasite is difficult to estimate for differing geographical areas (relative risk)
  • T cell immunity may be long lived (18-20 years)
  • Large study size and duration may be required where incidence is low
  • Resistance to artemisinin back-bone therapies is accelerating
  • Seasonal variance (rainy season offers increased vectoring of infection)
  • Placebo controlled trials may be less acceptable in highly endemic regions with risk of severe disease
hVIVO Human Challenge Models:
  • 100% infectivity in placebo
  • Exploration of vaccine efficacy & correlates of protection in relation to protection from infection, replication and disease
  • Study design matched to product mechanism of action (route of inoculation, species, lifecycle stage, naïve AND pre-immunes)
  • Parasitological Assays
  • Host Response Analysis
Primary & Secondary Endpoints:
  • Time to parasitaemia
  • Reduction in incidence of symptomatic infection
  • Reduction in disease severity

Antiviral/Treatments

Conceptual Challenges:

Establishing efficacy of antimalarials in early clinical trials is challenging

  • Resistant variants
  • Dose ranging / PK-PD / DDIs and drug vs parasite related AEs
  • Comorbidities and other confounders
hVIVO Human Challenge Models:
  • Timing - inoculation to recovery model
  • Study design matched to investigational product mechanism of actions
  • Optimisation of treatment / regimen dose and timing
  • Time-dependent measurements of biomarkers
  • Triggered-dosing options (time or parasitological)
  • Controlled strain exposure (NF54, vivax or MAL31)
  • Consistent placebo response
  • Resistance monitoring
Malaria Factsheet

If you’re a potential customer, job seeker, health professional or an investor, find out how hVIVO can help you.

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