Clinical trial NCT04037891: Topical rVA576 for Treatment of Atopic Keratoconjunctivitis
Official title: Topical rVA576 for Treatment of Atopic Keratoconjunctivitis: a Randomised Placebo-controlled Double Masked Parallel Trial (TRACKER)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Keratoconjunctivitis, Atopic
Keratoconjunctivitis, Vernal
Conjunctivitis, Allergic
Lead sponsor: AKARI Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-07-30
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Topical rVA576 for treatment of atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC),and severe allergic conjunctivitis (seasonal (SAC) or perennial (PAC)): a randomised placebo-controlled double masked parallel trial (TRACKER)

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

1. Aged 18 and above
2. Diagnosis of moderate to severe AKC, VKC, or severe allergic conjunctivitis (seasonal or perennial). Defined as:

   * AKC, VKC - a composite symptom/sign score from one eye of ≥ 18 out of 33
   * Severe allergic conjunctivitis (SAC or PAC) - a composite symptom/sign score from one eye of ≥ 15 out of 27
3. Will have had received some topical therapy during the last 3 months without improvement but will not currently be receiving systemic immunotherapy. Topical therapy may be topical calcineurin inhibitors, antihistamines or corticosteroids alone or in combination. Lubricants or artificial tears will not a count as topical therapy for these purposes.
4. Will have had at least 7 days without topical ocular corticosteroids prior to entry
5. Willing to give informed consent
6. Willing to use highly effective contraceptive precautions for the duration of the study and for 90 days after the last dose of IMP
7. Willing to avoid prohibited medications for duration of study (see list of prohibited medications)

Exclusion Criteria:

1. Eye surface disease other than AKC, VKC or severe allergic conjunctivitis (SAC or PAC)
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. Uncontrolled glaucoma (increase in dose of glaucoma medication or surgical intervention for glaucoma within 3 months prior to entry)
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. Use of topical ocular steroids within 7 days of the Screening visit
16. Failure to satisfy the PI of suitability to participate for any other reason

Primary outcomes:
measure: Incidence of Ocular TEAE
timeFrame: 56 days
Secondary outcomes:
measure: Post-instillation Comfort
timeFrame: Day 1 to 56
measure: Visual Acuity
timeFrame: Day 1 to 56
measure: Clinical Scores
timeFrame: Day 1 to 56
measure: MMP-9 Positive
timeFrame: Day 1 to 56
measure: Tear Film Break up Time
timeFrame: Change from Day 1 at Day 14, 28, 42 and 56
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Valladolid
country: Spain
facility: Instituto Universitario de Oftalmobiología Aplicada
city: Bristol
country: United Kingdom
facility: Bristol Eye Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NHS Foundation Trust
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Southend-on-Sea
country: United Kingdom
facility: University Hospital NHS Foundation Trust
Study officials:
affiliation: Moorfields Eye Hospital NHS Foundation Trust
name: Sajjad Ahmad
role: PRINCIPAL_INVESTIGATOR
References: