Clinical trial NCT02675803: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of VAY736 in Rheumatoid Arthritis Patients
Official title: A Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of VAY736 in Rheumatoid Arthritis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-02-05
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and tolerability as measured by the number of patients wth adverse events
timeFrame: 27-188 weeks
measure: Absolute bioavailability of VAY736: The ratio of area under curve (AUC) for s.c dose and for intravenous dose
timeFrame: 188 weeks
measure: Plasma pharmacokinetics of VAY736: The area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCtau)
timeFrame: 27 weeks
measure: Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
timeFrame: 27 weeks
measure: Plasma pharmacokinetics of VAY736: Observed maximum plasma concentration following drug administration (Cmax)
timeFrame: 27 weeks
measure: Plasma pharmacokinetics of VAY736: Time to reach the maximum concentration after drug administration (Tmax)
timeFrame: 27 weeks
measure: Plasma pharmacokinetics of VAY736: The terminal elimination half-life (T1/2)
timeFrame: 27 weeks
measure: Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
timeFrame: 27 weeks
measure: Plasma pharmacokinetics of VAY736: concentration of VAY736 during the treatment period, before each dose (Ctrough)
timeFrame: 27 weeks
measure: Safety and tolerability as measured by the percentage of patients wth adverse events
timeFrame: 27-188 weeks
Secondary outcomes:
measure: pharmacodynamics of VAY736
timeFrame: 27-188 weeks
measure: Immunogenicity of VAY736
timeFrame: 27-188 weeks
measure: Plasma bioavailability of VAY736: The ratio of area under curve (AUC) for repeated s.c doses and for intravenous dose
timeFrame: 27 weeks
measure: Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
timeFrame: 34-188 weeks
measure: Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
timeFrame: 34-188 weeks
measure: Plasma pharmacokinetics of VAY736: Observed maximum plasma concentration following drug Administration (Cmax)
timeFrame: 34-188 weeks
measure: Plasma pharmacokinetics of VAY736: Time to reach the maximum concentration after drug administration (Tmax)
timeFrame: 34-188 weeks
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: