Distribution of Secukinumab (AIN457) Into Dermal Interstitial Fluid After a Single Subcutaneous Administration of 300 mg

Novartis Pharmaceuticals16 enrolled

Overview

The proposed exploratory study aims to understand the in vivo skin distribution properties of subcutaneously (s.c.) administered AIN457 in psoriatic and healthy skin using open flow microperfusion (OFM). The data of this study will help to understand the mode of action of AIN457 in its target tissue. It aims to establish a technique assessing in vivo distribution of AIN457 and its metabolites in human dermal interstitial fluid (ISF) and exploring a potential pharmacodynamic effect in situ. In addition, the study will further evaluate safety and local tolerability of subcutaneously administered AIN457 and explore dermal interstitial fluid skin levels of potential disease relevant biomarkers. The study is divided into two parts - Part I with 8 healthy volunteers (HV) to validate the method is completed and Part II with 8 psoriasis patients will start based on the outcome of Part I.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Healthy Psoriasis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

For Part I : Healthy male and female subjects 18 to 65 years of age inclusive; For Part II: Chronic plaque-type psoriasis (with or without arthritis) diagnosed for at least 6 months before enrollment including at least one plaque accessible for OFM with at least moderate severity ; Key exclusion criteria for Part I and Part II: Women of child-bearing potential unwilling to use effective contraception; History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection as defined by a positive TB-test at screening; For Part I: Use of any prescription drugs, herbal supplements, within 4 weeks prior to initial dosing For Part II: Ongoing use of concomitant psoriasis treatments. Washout periods have to be adhered to. Other protocol-defined inclusion/exclusion criteria may apply.

Outcomes

Primary Outcomes

Amount (ng/ml) of AIN457 in dermal interstitial fluid.

Distribution of AIN457 into dermal interstitial fluid after single subcutaneous administration of AIN457 in healthy subjects and in psoriatic patients

Time frame: Day 8

Amount (ng/ml) of AIN457 in dermal interstitial fluid.

Distribution of AIN457 into dermal interstitial fluid after single subcutaneous administration of AIN457 in healthy subjects and in psoriatic patients

Time frame: Day 15

Secondary Outcomes

Number of adverse events to measure Safety of subcutaneously administered AIN457 in healthy volunteers and psoriatic patients

Safety of AIN457 s.c. injection will be documented as numbers of adverse event.

Time frame: 3 weeks

Part I only: concentration of sinistrin in serum vs. dermal interstitial fluid to confirm the ability of sinistrin to serve as reference to quantify AIN457 in dermal interstitial fluid.

Concentration of sinistrin in serum compared to dermal interstitial fluid.