Topical rVA576 for Treatment of Atopic Keratoconjunctivitis

Incidence of ocular treatment-emergent adverse events (TEAE) during the treatment period which have occurred during the 56 days following randomisation.

Time frame: 56 days

Change from Day 1 in composite clinical scores at Day 14, 28, 42 and 56, for the eye judged as worst affected at each visit. Score calculated from symptom and sign sub-components. AKC/VKC: symptom sub-component consisted of itch, tearing, discomfort, discharge, and photophobia, and the sign component consisted of bulbar conjunctival hyperaemia, tarsal conjunctival papillary hypertrophy, punctate keratitis, neovascularization of cornea, cicatrizing conjunctivitis, blepharitis. SAC/PAC: symptom sub-component consisted itch, tearing, discomfort, and photophobia, and the sign sub-component consisted of upper tarsal conjunctival hyperaemia, upper bulbar conjunctival hyperaemia, chemosis, upper tarsal conjunctival papillae, blepharitis. For each sign/symptom a score of 0 - 3 is awarded (0=absence of a sign/symptom; an increase in score indicates increase in severity). These scores are summed at the end of the exam to give the composite score. Range:0 to 33 (AKC/VKC) or 27 (SAC/PAC).

Time frame: Day 1 to 56

Population: Because only two patients in the Part 2 nomacopan group had data to assess this score, it is not meaningful to compare the nomacopan and placebo groups, and so further analysis was not performed.~Note there were two patients on Placebo with SAC; therefore, scored on a different scale compared to patients with AKC or VKC. For the purposes of the outcome measure, the SAC and AKC/VKC scores were combined to derive a single value across all participants.

Percentage of patients with Matrix metalloprotease 9 (MMP-9) positive levels at Days 1, 28, and 56. MMP-9 is a is a nonspecific inflammatory marker. Detection was made using the Inflammadry® device. This device gives a binary (positive/negative) result.

Time frame: Day 1 to 56

Population: There were too few patients to make a meaningful interpretation.

Graded on patient diary cards at the intervals Day 1-14, 15-28, 29-42 and 43-56. Eye comfort scoring: 0 - Perfectly comfortable 1. \- Slight discomfort. Some burning, itching or stinging for up to half a minute after using the eye drop, solution but the discomfort improves without treatment. 2. \- Moderate discomfort. Burning, itching or stinging lasts for 0.5 minute or longer but improves without treatment. 3. \- Severe discomfort. Burning, itching or stinging last for at least 0.5 minute and requires washing the eyes to relieve it. 4. \- Unbearable burning itching or stinging. So severe that you cannot continue treatment. The 14 day average score for each interval have been calculated for each patient (possible range of 0 to 40). Classifications were assigned using the average total score at each two week period as follows: \< 10 = Comfortable/Acceptable, 10 - 19 = Moderately Uncomfortable, 20 - 29 = Very Uncomfortable, \>= 30 = Severely/Unacceptably Uncomfortable.

Time frame: Day 1 to 56

Population: The Comfort score data was not available for one patient in the nomacopan group Part 2, and in one patient in Part 1, after Day 14, both due to withdrawal.~Because only two patients in the Part 2 nomacopan group had data to assess comfort score, it is not meaningful to compare the nomacopan and placebo groups, and so further analysis was not performed.

Change from Day 1 in Tear film break up time (TBUT) at Day 14, 28, 42 and 56. TBUT data was available for one eye only. Tear breakup time (TBUT) is a clinical test used to assess for evaporative dry eye disease. To measure TBUT, fluorescein is instilled into the patient's tear film and the patient is asked not to blink while the tear film is observed under a broad beam of cobalt blue illumination. The TBUT is recorded as the number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film. A TBUT under 10 seconds is considered abnormal.

Time frame: Change from Day 1 at Day 14, 28, 42 and 56

Population: Patient numbers within each treatment group are too small to make meaningful comparisons, and so no further analysis was performed.

Visual acuity for the worst eye over time by Early Treatment Diabetic Retinopathy Study (ETDRS) charts comparison from Day 1 to Day 56 In ETDRS charts, zero indicates standard vision, positive values indicates poor vision, and negative values indicates good vision.

Time frame: Day 1 to 56

Population: Only one patient in the nomacopan group in Part 2 had data to assess this score. It is not meaningful to compare the nomacopan and placebo groups, and so further analysis was not performed.