Malaria

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 unmet 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.

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

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

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

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.

Reported symptoms are mostly mild to moderate and include headache, fever, nausea and fatigue.

Vaccines

Conceptual Challenges

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

  • Initial exposure to virus unknown

  • Variation in circulating strains

  • Large study size and duration

  • Difficult to power for clinical efficacy

  • Seasonality limitations

  • Biomarker identification difficult

Vaccines

hVIVO Human Challenge Models: Towards a deeper understanding
  • Effective exploration of vaccine efficacy & correlates of protection

  • Match study design to product mechanism of action

  • Immunological Assays

  • Host Response Analysis

Primary & Secondary Endpoints:

  • Time to parasitaemia

  • Reduction in incidence of symptomatic infection

  • Reduction in disease severity

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Antiviral/Treatments

Conceptual Challenges

Establishing efficacy of antivirals in early clinical trials is challenging

  • Initial exposure to virus unknown

  • Dose ranging and timing difficult

  • Comorbidities and other confounders

Antiviral/Treatments

hVIVO Human Challenge Models: Towards a deeper understanding

Clinical proof-of concept and dosing finding delivered in a controlled setting

  • Study design matched to investigational product mechanism of actions

  • Optimisation of treatment timing

  • Time-dependent measurements of biomarkers

  • Triggered-dosing options (time or virological)

  • Controlled strain exposure

  • Consistent placebo response

  • Efficient resistance monitoring

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Immunomodulator

Conceptual Challenges

Demonstrating clinical efficacy in early stage field trials is challenging

  • Baseline prior to infection unachievable, difficult to establish host response

  • Effect with/without standard of care treatment difficult to establish

  • Large study size and duration

  • Circulating strain variation

  • Biomarker identification difficult

  • Initial exposure to virus unknown

Immunomodulator

hVIVO Human Challenge Models: Towards a deeper understanding

Clinical proof-of concept and dosing finding delivered in a controlled setting

  • Well controlled quarantine environments

  • Baseline well established prior to infection

  • Appropriate for both prophylaxis and treatment

  • Flexible dosing and timing

  • Establish safety & efficacy to impact infected subjects host response

  • Investigate and demonstrate target engagement

  • Controlled combination-treatment with drug and standard of care or antivirals

Malaria Scientific Papers / Abstracts