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HRV Challenge Studies

A well characterised rhinovirus, practiced across the globe

The Challenge

Human rhinoviruses (HRV) are some of the most commonly isolated viral pathogens in people suffering with ‘the common cold’. Over 150 antigenically distinct types of HRV are currently known and these different serotypes span three species: HRV A, HRV B, and HRV C. Rhinovirus infection primarily results in mild upper respiratory tract disease (approximately 50% of all URTIs) and infection rates among young children can be as high as 8–12 times a year. HRV infections are known to be an important predisposing factor to conditions such as sinusitis, otitis media, bronchitis and primary pneumonia, inclusive of secondary bacterial infections. Rhinovirus infections are also linked to asthma exacerbations in children, and this predisposition may persist into adulthood!,500d.

Rhinoviruses are known to precipitate serious disease states in the elderly, immune compromised and those with existing respiratory diseases. There is strong epidemiological evidence of a relationship between rhinovirus infection and exacerbation of asthma and chronic obstructive pulmonary disease (COPD). To date, no antiviral agent has been approved in the prevention or treatment of rhinovirus infection and clinical treatment is directed towards addressing symptoms of the disease only (supportive care).

The Model

hVIVO has an approved and well characterised rhinovirus (HRV-16) that has been used to safely infect individuals in a large number of viral challenge studies carried out at the main hVIVO containment unit in London. 

Markers associated with the primary endpoints for HRV studies, such as infection rates, as measured by viral shedding (peak viral load and viral area under curve (vAUC)), and disease (the clinical syndrome or symptoms associated with experimental infection) are consistent and may be captured from the time of inoculation through to recovery and discharge of the subject.

Volunteers for a rhinovirus study are pre-screened for anti-HRV-16 antibodies to look for immunity to the challenge virus. Naïve or serosusceptible individuals are progressed to further screening relating to protocol associated inclusion and exclusion criteria. Over 373 subjects have been safely infected with HRV to date and this model is widely accepted and practiced across the globe in the investigation of new treatments for the common cold.

As the industry leader in conducting human viral challenge studies, hVIVO have developed a large Virobase, of clinical data paired with virological data, host genetics and immunology combined with an extensive biorepository of blood and respiratory samples. This “Virometrics” resource, in conjunction with our unique insight into the host response to viral disease, allows hVIVO to tailor study designs to each IMP.

Validated Human Rhinovirus Model

Challenge with HRV-16 produces infection in up to 90% of susceptible volunteers. Symptoms usually first appear within 24 hours after inoculation and peak at 48-72 hours. The clinical syndrome is comparable to that reported in natural colds. Approximately one-third of rhinovirus infections, whether natural or experimental, are asymptomatic.

HRV-16 challenge trials may be used to test both prophylactics (i.e. drugs and vaccines that prevent infection and disease) or therapeutics (i.e. mainly drugs used to treat disease once an infection is established).

Successful Subjects

Over 373 subjects have been safely infected with Human Rhinoviruses to date and this model is widely accepted and practiced across the globe in the investigation of new treatments for the common cold.

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
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:
  • Reduction in incidence of symptomatic infection
  • Reduction in disease severity

Antivirals/Treatments

Conceptual Challenges:

Establishing efficacy of antivirals in early clinical trials is challenging Comor

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

Immunomodulators

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
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
HRV Factsheet

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