Pivotal trial results for vernal conjunctivitis drug released

Key Points

Evry, France-Results of a pivotal phase III trial of a cyclosporine A product (Vekacia, Novagali Pharma) for the treatment of vernal conjunctivitis (VKC) in children showed that the drug improved symptoms and signs of the orphan disease, and tolerability was excellent, according to the manufacturer.

VKC, a severe form of chronic allergic conjunctivitis characterized by ocular discomfort, pain, itching, and intense photophobia, is a rare disease that mostly affects children and young adults living in warm climates.

The study was designed as a clinical phase II/III, multicenter, randomized, parallel group, double-masked, dose-ranging, controlled trial divided in two treatment periods: a 4-week prospective, randomized, multicenter, double-masked, three-parallel-group, vehicle-controlled treatment period; and a 3-month prospective, multicenter, double-masked treatment period.

The primary objective of the phase III study was to assess the efficacy of the drug's 0.05% formulation and 0.1% formulation, administered four times daily, versus a vehicle after a 4-week treatment period for patients with VKC. The secondary objectives were to compare the safety, ocular tolerance (objective and subjective), and long-term safety after 4 months.

The study included 118 patients (mean age, 8.8 years) with active bilateral VKC (acute or chronic); they enrolled in the study at more than 21 sites in Europe and Mediterranean countries from May to October 2006. Most patients (90 patients, 76.3%) were suffering from perennial VKC and presented at study entry with a mixed form of VKC (87 patients, 73.7%).

The superiority of the cyclosporine A product over its vehicle was demonstrated by the statistically significant improvement of both objective signs of VKC and keratitis in treated patients. Both doses were safe and well tolerated. Local tolerance at instillation was satisfactory and, therefore, adherence to the recommended dose regimen of four instillations per day was good. Systemic exposure to cyclosporine A was negligible in the treated patients. Adherence with the study regimen of four daily instillations of the drug was excellent.

Overall improvement of subjective symptoms (burning/stinging, tearing, itching, pain, sticky eyelids, foreign body sensation, mucus discharge, and photophobia) was superior to the vehicle for both concentrations of the drug. For objective signs (conjunctival erythema/hyperemia, conjunctival chemosis and discharge, papillae, limbal infiltrates, and corneal epithelial disease), a statistically significant difference was seen between both concentrations of the drug and the vehicle treatment (p = 0.0386 and p = 0.0208 for the 0.05% formulation and the 0.1% formulation treatment arms, respectively). Similarly, improvement in superficial keratitis was statistically significant with the 0.05% formulation versus vehicle (p = 0.0176).

At 1 month, seven patients had withdrawn from the study-four patients using the vehicle, and three patients using the drug; the latter group of patients included one case of ocular intolerance following study drug instillation. Few treatment-emergent adverse effects were reported, the most frequent being eye disorders of mild intensity.

The tested formulations were rated as comfortable by 94.4% (vehicle), 79.5% (0.05% formulation), and 80.6% (0.1% formulation). Blood levels of cyclosporine A were assayed after 1 month of treatment in 16 patients treated with the drug, and five patients had detectable cyclosporine A levels below 0.33ng/ml, a value considered negligible.