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

Rheumatoid Arthritis Clinical Trial

Official title:

A Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of VAY736 in Rheumatoid Arthritis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02675803
• Other study ID #: CVAY736X2101
• Secondary ID: 2010-020156-65
• Status: Completed
• Phase: Phase 1
• Start date: December 20, 2010
• Est. completion date: January 22, 2018

Study information

• Verified date: January 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: January 22, 2018
• Est. primary completion date: January 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• VAY736
VAY736 treatment
• VAY736 placebo
VAY736 placebo

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	27-188 weeks
Primary	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	188 weeks
Primary	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	27 weeks
Primary	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.	27 weeks
Primary	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	27 weeks
Primary	Plasma pharmacokinetics of VAY736: Time to reach the maximum concentration after drug administration (Tmax)	In Part 3: After the first and last s.c. doses, the time to reach the maximum concentration after drug administration (Tmax) will be determined	27 weeks
Primary	Plasma pharmacokinetics of VAY736: The terminal elimination half-life (T1/2)	In Part 3: After the first and last s.c. doses, the terminal elimination half-life (T1/2) will be determined	27 weeks
Primary	Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)	In Part 3: After the first and last s.c. doses, Area under the plasma concentration-time curve from time zero to infinity (AUCinf) will be determined.	27 weeks
Primary	Plasma pharmacokinetics of VAY736: concentration of VAY736 during the treatment period, before each dose (Ctrough)	In Part 3: After the first and last s.c. doses, the concentration of VAY736 during the treatment period, before each dose (Ctrough) will be determined	27 weeks
Primary	Safety and tolerability as measured by the percentage of patients wth adverse events	Part 1 The percentage 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 recovery criteria.; Part 2 The percentage 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 68 weeks post dose or until B cells reach recovery criteria..; Part 3 The percentage 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.	27-188 weeks
Secondary	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	27-188 weeks
Secondary	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.	27-188 weeks
Secondary	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	27 weeks
Secondary	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	34-188 weeks
Secondary	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.	34-188 weeks
Secondary	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	34-188 weeks
Secondary	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	34-188 weeks

External Links

•   A Plain Language Trial Summary is available on novartisclinicatrials.com
•   Results for CVAY736X2101 from the Novartis Clinical Trials Website