Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 92 of 2725 for:    Rheumatoid Arthritis

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02675803
Recruitment Status : Completed
First Posted : February 5, 2016
Last Update Posted : January 8, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Biological: VAY736 Biological: VAY736 placebo Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of VAY736 in Rheumatoid Arthritis Patients
Actual Study Start Date : December 20, 2010
Actual Primary Completion Date : January 22, 2018
Actual Study Completion Date : January 22, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: VAY736
VAY736 active
Biological: VAY736
VAY736 treatment

Placebo Comparator: Placebo
VAY736 placebo
Biological: VAY736 placebo
VAY736 placebo




Primary Outcome Measures :
  1. Safety and tolerability as measured by the number of patients wth adverse events [ Time Frame: 27-188 weeks ]

    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.


  2. Absolute bioavailability of VAY736: The ratio of area under curve (AUC) for s.c dose and for intravenous dose [ Time Frame: 188 weeks ]
    Part 2 The ratio of area under curve (AUC) for single s.c dose and intravenous dose is determined

  3. Plasma pharmacokinetics of VAY736: The area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCtau) [ Time Frame: 27 weeks ]

    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


  4. Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) [ Time Frame: 27 weeks ]

    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.


  5. Plasma pharmacokinetics of VAY736: Observed maximum plasma concentration following drug administration (Cmax) [ Time Frame: 27 weeks ]

    In Part 3:

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


  6. Plasma pharmacokinetics of VAY736: Time to reach the maximum concentration after drug administration (Tmax) [ Time Frame: 27 weeks ]

    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


  7. Plasma pharmacokinetics of VAY736: The terminal elimination half-life (T1/2) [ Time Frame: 27 weeks ]

    In Part 3:

    After the first and last s.c. doses, the terminal elimination half-life (T1/2) will be determined


  8. Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to infinity (AUCinf) [ Time Frame: 27 weeks ]

    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.


  9. Plasma pharmacokinetics of VAY736: concentration of VAY736 during the treatment period, before each dose (Ctrough) [ Time Frame: 27 weeks ]

    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


  10. Safety and tolerability as measured by the percentage of patients wth adverse events [ Time Frame: 27-188 weeks ]

    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.



Secondary Outcome Measures :
  1. pharmacodynamics of VAY736 [ Time Frame: 27-188 weeks ]
    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

  2. Immunogenicity of VAY736 [ Time Frame: 27-188 weeks ]
    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.

  3. Plasma bioavailability of VAY736: The ratio of area under curve (AUC) for repeated s.c doses and for intravenous dose [ Time Frame: 27 weeks ]
    Part 3 The ratio of area under curve (AUC) for repeated s.c doses and for intravenous dose is determined

  4. Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) [ Time Frame: 34-188 weeks ]
    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

  5. Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to infinity (AUCinf) [ Time Frame: 34-188 weeks ]
    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.

  6. Plasma pharmacokinetics of VAY736: Observed maximum plasma concentration following drug Administration (Cmax) [ Time Frame: 34-188 weeks ]
    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

  7. Plasma pharmacokinetics of VAY736: Time to reach the maximum concentration after drug administration (Tmax) [ Time Frame: 34-188 weeks ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02675803


Locations
Layout table for location information
Germany
Novartis Investigative Site
Berlin, Germany, 10117
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Additional Information:
Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02675803     History of Changes
Other Study ID Numbers: CVAY736X2101
2010-020156-65
First Posted: February 5, 2016    Key Record Dates
Last Update Posted: January 8, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Rheumatoid arthritis

Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases