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NCT Number: NCT02675803

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

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.

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Key information

Conditions

Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site

Berlin, 10117, Germany

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

VAY736

Biological

VAY736 treatment

VAY736 placebo

Biological

VAY736 placebo

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

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

Important dates

Study start
2010
Primary completion
2018
Study completion
2018
First posted
Feb 5, 2016
Registry last updated
Dec 11, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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