Topical rVA576 for Treatment of Atopic Keratoconjunctivitis
Topical rVA576 for Treatment of Atopic Keratoconjunctivitis
Topical rVA576 for treatment of atopic keratoconjunctivitis: a randomised placebo-controlled
 double masked parallel trial (TRACKER)
Recombinant rVA576 is a small protein (16.7kDa) which has two independent actions. It
 inhibits the activation and cleavage of complement C5 and it binds and inactivates
 leukotriene B4 (LTB4). It acts on the complement system by preventing the cleavage of C5 by
 C5 convertase into C5a and C5b and so is effective in inhibiting terminal complement activity
 irrespective of the activating pathway.

 Atopic keratoconjunctivitis (AKC) is a type of allergic conjunctivitis which involves mast
 cell activation due to the predominance of inflammatory mediators such as eosinophils and
 Th2-generated cytokines (Mishra et al. 2011).

 Recombinant rVA576 eye drops solution is the investigational medicinal product. It is
 intended for ophthalmic use by topical administration to the eye.

 Recombinant rVA576 is a compact small protein molecule with a lipocalin-like structure
 consisting of alpha helices and a beta barrel. There is a surface-active site which binds to
 the complement C5 molecule with a high affinity (KD 1.85 x 10-8 M) and an internalised active
 site which binds the small eicosinoid molecule leukotriene B4 (Hepburn et al. 2007).
Inclusion Criteria:

 1. Aged 18 and above

 2. Diagnosis of moderate to severe AKC with a composite symptom/sign score from one eye
 of ≥ 22 out of 33 (see Clinical Scoring 17.1)

 3. Will have had maximal topical therapy for at least 3 months without improvement but
 will not currently be receiving systemic immunotherapy.

 4. History of atopy other than ocular (dermatitis, asthma, hay fever)

 5. Willing to give informed consent

 6. Willing to use adequate contraceptive precautions for the duration of the study and
 for 90 days thereafter

 7. Willing to avoid prohibited medications for the duration of the study

 Exclusion Criteria:

 1. Eye surface disease other than AKC

 2. Contact lens use during the study

 3. Complete or partial tarsorrhaphy. If such a procedure becomes necessary during the
 course of the trial patients may remain in the trial providing that at least 50% of
 the eye surface remains visible to slit lamp examination

 4. Ankyloblepharon of any degree at entry to the trial

 5. Known or suspected ocular malignancy

 6. Active ocular infection at entry to the trial. Patients with eye surface bacterial,
 viral, fungal or protozoal infection may enter the trial after elimination of the
 infection as confirmed by eye swabs

 7. Known or suspected uveitis

 8. Participation in any other clinical trial within 1 month of enrolment

 9. Use of any of the following prohibited medications:

 -  Eculizumab

 -  Any other investigational complement inhibitor whether systemic or topical (e.g.
 RA101495)

 -  Montelukast

 -  Zafirlukast

 -  Pranlukast

 -  Zileuton

 -  Hypericum perforatum (St John's wort)

 10. Corneal perforation

 11. Glaucoma

 12. Pregnancy (females)

 13. Breast feeding (females)

 14. Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom)

 15. Failure to satisfy the PI of suitability to participate for any other reason