Study of Efficacy and Safety of VAY736 in Patients With Pemphigus Vulgaris

A Randomized, Partial-blind, Placebo-controlled Trial Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of VAY736 in the Treatment of Patients With Pemphigus Vulgaris

The study recruitment was terminated in Dec-2015 for strategic reasons related to the development of the compound.

The study evaluated the efficacy, safety and pharmacokinetics of VAY736 in the treatment of patients with pemphigus vulagaris (PV).

This was a non-confirmatory, randomized, partial-blind, placebo-controlled trial evaluating the efficacy, safety and pharmacokinetics (PK) of VAY736 in the treatment of PV patients. A total of 13 patients were enrolled and randomized into the study. Of these 13 patients,seven were randomized to the 3 mg/kg VAY736 group, two were randomized to the 10 mg/kg VAY736 group and four were randomized to the placebo group.In the placebo group, three out of the four patients consented to open-label VAY736 treatment and received 10 mg/kg VAY736 after Week 24 onwards. Thus, a total of 12 patients received VAY736, 7 patients received 3 mg/kg and 5 patients 10 mg/kg. The Screening period consisted of a Screening Visit performed within 28 days prior to randomization to assess patient eligibility. Following Screening, patients underwent pre-dose procedures which included assessment of their PV by Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin disease Intensity Score (ABSIS) and Investigator Global Assessment (IGA), and blood sampling for PK endpoints. Patients then received the study drug, which was administered over approximately a 2 hour period. The patients remained in the study center overnight post-infusion for observation and for measurement of safety parameters and PK samples approximately 24 h post-infusion (start of infusion: ±2 h). Patients were then discharged from the study site and returned as per the schedule. Patients were evaluated at Week 1, Week 2 and Week 3, then every 3 weeks through to Week 12, and every 4 weeks through to Week 24. At Week 24, the blind was broken to confirm treatment allocation. If a patient was on placebo, such patient completing the Week 24 visit and after unblinding had the option of receiving open label VAY736 10mg/kg. Recruitment was paused in Mar-2015 and at the time 13 patients were enrolled. The study recruitment was then terminated in Dec-2015 for strategic reasons related to the development of the compound.

single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo.

PDAI is specific cutaneous and mucosal disease activity assessment performed by investigator based on evaluation of lesions in well-defined anatomical locations. The score weighted for the number and size of lesions with score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Damage, such as post inflammatory hyperpigmentation or erythema from resolving lesion, scored separately from the main score as absent (0) or present (1) for each body area or scalp resulting in a score of 0 to 12 or 0 to 1, respectively. Thus, PDAI ranged from 0 to 263, with 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity) and 13 points representing disease damage.

The ABSIS Score is a quality- and quantity-based score for cutaneous and oral mucosal lesions combining the extent of the affected body surface area (BSA), the quality of the skin lesions and oral involvement. The ABSIS score ranged from 0 to 206 with 150 points for skin involvement, 11 points for oral involvement and 45 points for subjective discomfort during eating and drinking. A reduction from baseline (or, a negative change from baseline) in ABSIS indicates improvement in patients.

The IGA score ranges from 0 to 4 and the decrease or reduction from baseline in IGA score indicates improvement in patients. IGA score scale: 0=Clear, 1=Near Clear, 2=Mild, 3=Moderate, 4=Severe active disease

The area under the serum concentration-time curve from time zero to infinity [mass × time / volume]. The concentration of VAY736 was measured in the serum.

The area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration [mass × time / volume]. The concentration of VAY736 was measured in the serum.

The observed maximum serum concentration following drug administration [mass / volume]. The concentration of VAY736 was measured in the serum.

Tmax is the time to reach the maximum concentration after drug administration [time]. The concentration of VAY736 was measured in the serum.

T1/2 is the terminal elimination half-life [time]. The concentration of VAY736 was measured in the serum.

Inclusion Criteria: Adult patients 20 to 70 years of age Confirmed diagnosis of pemphigus vulgaris Presence of mild to moderate pemphigus vulgaris Patients must weight between 40 kg and 150 kg inclusive on a stable dose of oral corticosteriod therapy (with or without azathioprine or mycophenolate) Exclusion Criteria: Pregnant or nursing (lactating) women Women of child-bearing potential unless they are using a highly effective method of birth control during dosing and for 4 months following study treatment Recent previous treatment with photo therapy, biological therapy, steroids, immunosuppresive agents (unless washout period applied) Active or recent history of clinically significant infection use of rituximab within 1 year Other protocol-defined inclusion/exclusion criteria may apply.

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com