Clinical trial NCT01930175: Study of Efficacy and Safety of VAY736 in Patients With Pemphigus Vulgaris
Official title: A Randomized, Partial-blind, Placebo-controlled Trial Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of VAY736 in the Treatment of Patients With Pemphigus Vulgaris
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pemphigus Vulgaris
Keywords: Pemphigus vulgaris
pemphigus
blistering disease
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-08-28
Enrollment: 13
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pemphigus Disease Area Index (PDAI) at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Autoimmune Skin Disease Intensity Score (ABSIS) at Baseline and Week 12.
timeFrame: Baseline, Week 12
measure: Change From Baseline in Investigator Global Assessment (IGA) at Week 12
timeFrame: Baseline, Week 12
measure: VAY736 Serum Concentration - AUCinf
timeFrame: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks
measure: VAY736 Serum Concentration - AUClast
timeFrame: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks
measure: VAY736 Serum Concentration - Cmax
timeFrame: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks
measure: VAY736 Serum Concentration - Tmax
timeFrame: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks
measure: VAY736 Serum Concentration - T1/2
timeFrame: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
state: BGR
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: