Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of VAY736 in Rheumatoid Arthritis Patients

Novartis Pharmaceuticals65 enrolled

Overview

This study investigated the safety and tolerability of VAY736 administered as single ascending doses of intravenous infusion, subcutaneous injection and repeated subcutaneous injections in rheumatoid arthritis patients.

This study had three sequential parts which investigated the safety and tolerability of VAY736 administered as single ascending doses of intravenous infusion (Part 1), single ascending doses of subcutaneous injection (Part 2), and repeated subcutaneous injections of fixed doses (Part 3), respectively, in rheumatoid arthritis patients. Part 1 was double blind, placebo controlled, with 11 cohorts. Part 2 was open-label study with 2 dosing cohorts. Part 3 was open-label study with 1 fixed-dose cohort.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Rheumatoid Arthritis

Interventions

VAY736BIOLOGICAL

VAY736 treatment

VAY736 placeboBIOLOGICAL

VAY736 placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Active disease despite methotrexate treatment 5 to 20 mg/week for Parts 1 and 2; methotrexate treatment 5 to 20 mg/week for Part 3 * Fulfilled 2010 American College of Rheumatolody (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis for Part 1 and Part 2. For Part 3, fulfilled 2010 American College of Rheumatolody (ACR)/)/European League Against Rheumatism (EULAR) classification criteria or/and 1987 American College of Rheumatolody (ACR) classification criteria for rheumatoid arthritis; * Methotrexate ≥ 16 weeks, stable dose ≥ 8 weeks Exclusion Criteria: * Previous treatment with a B cell-depleting biologic agent. * Autoimmune disease other than RA except concurrent Sjogren's syndrome * Adult juvenile rheumatoid arthritis * ARA functional class IV disease of ACR Revised Steinbrocker Classification

Locations (1)

Novartis Investigative Site

Berlin, Germany

Outcomes

Primary Outcomes

Safety and tolerability as measured by the number of patients wth adverse events

Part 1 The number of patients with adverse events after single intravenous (i.v.) dose of VAY736. Patients are assessed weekly up to 34 weeks post dose or until B cells reach the recovery criteria Part 2 The number of patients with adverse events after single subcutaneous (s.c.) dose of VAY736. Patients are assessed weekly, bi-weekly, then every 4, 8 and 12 weeks up to 188 weeks post dose or until B cells reach the recovery criteria. Part 3 The number of patients with adverse events after repeated subcutaneous (s.c) injections of a fixed dose of VAY736. Patients are assessed bi-weekly, then every 4 weeks and 8 weeks up to 27 weeks from the first dose.

Time frame: 27-188 weeks

Absolute bioavailability of VAY736: The ratio of area under curve (AUC) for s.c dose and for intravenous dose

Part 2 The ratio of area under curve (AUC) for single s.c dose and intravenous dose is determined

Time frame: 188 weeks

Plasma pharmacokinetics of VAY736: The area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCtau)

In Part 3: After the first and last s.c. doses, the area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCtau) will be determined

Time frame: 27 weeks

Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)

In Part 3: After the first and last s.c. doses, the Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) will be determined.

Time frame: 27 weeks

Plasma pharmacokinetics of VAY736: Observed maximum plasma concentration following drug administration (Cmax)

In Part 3: After the first and last s.c. doses, the Observed maximum plasma concentration following drug administration (Cmax) will be determined

Data from ClinicalTrials.gov

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Secondary Outcomes

pharmacodynamics of VAY736

B cell depletion/recovery after single i.v. dose of VAY736, single s.c. dose of VAY736 and multiple fixed s.c. doses of VAY736 administration in the 3 parts of the study

Time frame: 27-188 weeks

Immunogenicity of VAY736

Immunogenicity after administration of single i.v. dose of VAY736, single s.c. dose of VAY736 and multiple fixed s.c. doses of VAY736 in 3 parts of the study.

Time frame: 27-188 weeks

Plasma bioavailability of VAY736: The ratio of area under curve (AUC) for repeated s.c doses and for intravenous dose

Part 3 The ratio of area under curve (AUC) for repeated s.c doses and for intravenous dose is determined

Time frame: 27 weeks

Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)

The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) will be determined after single i.v. dose and s.c. dose of VAY736 in Part 1 and Part 2 respectively

Time frame: 34-188 weeks

Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)

The area under the plasma concentration-time curve from time zero to infinity (AUCinf) will be determined after single i.v. dose and s.c. dose of VAY736 in Part 1 and Part 2 respectively.

Time frame: 34-188 weeks

Plasma pharmacokinetics of VAY736: Observed maximum plasma concentration following drug Administration (Cmax)

The Observed maximum plasma concentration following drug administration (Cmax) will be determined after single i.v. dose and s.c. dose of VAY736 in Part 1 and Part 2 respectively

Time frame: 34-188 weeks

Plasma pharmacokinetics of VAY736: Time to reach the maximum concentration after drug administration (Tmax)

The time to reach the maximum concentration after drug administration (Tmax) will be determined after single i.v. dose and s.c. dose of VAY736 in Part 1 and Part 2 respectively

Time frame: 34-188 weeks