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.

Here at hVIVO, we are 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 participants have received 2,011 doses of Sanaria PfSPZ Challenge (NF54) with no deaths, unresolved significant adverse events, or sequelae to date. We have 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

Our 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

Our 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 Challenge Model

The Challenge

Validated Malaria Model

"Overall efficient, clear and professional communications and project management"

Vaccine Trials

Conceptual Challenges:

Our Human Challenge Models:

Primary & Secondary Endpoints:

Antiviral/Treatments

Conceptual Challenges:

Our Human Challenge Models:

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