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

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
VAY736
VAY736 placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

VAY736

Placebo

Arm Description

VAY736 active

VAY736 placebo

Outcomes

Primary Outcome Measures

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.
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
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
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.
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
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
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
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.
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
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.

Secondary Outcome Measures

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
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.
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
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
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.
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
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

Full Information

First Posted
July 9, 2015
Last Updated
December 9, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02675803
Brief Title
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

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
December 20, 2010 (Actual)
Primary Completion Date
January 22, 2018 (Actual)
Study Completion Date
January 22, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
65 (Actual)

8. Arms, Groups, and Interventions

Arm Title
VAY736
Arm Type
Experimental
Arm Description
VAY736 active
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
VAY736 placebo
Intervention Type
Biological
Intervention Name(s)
VAY736
Intervention Description
VAY736 treatment
Intervention Type
Biological
Intervention Name(s)
VAY736 placebo
Intervention Description
VAY736 placebo
Primary Outcome Measure Information:
Title
Safety and tolerability as measured by the number of patients wth adverse events
Description
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
Title
Absolute bioavailability of VAY736: The ratio of area under curve (AUC) for s.c dose and for intravenous dose
Description
Part 2 The ratio of area under curve (AUC) for single s.c dose and intravenous dose is determined
Time Frame
188 weeks
Title
Plasma pharmacokinetics of VAY736: The area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCtau)
Description
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
Title
Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
Description
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
Title
Plasma pharmacokinetics of VAY736: Observed maximum plasma concentration following drug administration (Cmax)
Description
In Part 3: After the first and last s.c. doses, the Observed maximum plasma concentration following drug administration (Cmax) will be determined
Time Frame
27 weeks
Title
Plasma pharmacokinetics of VAY736: Time to reach the maximum concentration after drug administration (Tmax)
Description
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
Time Frame
27 weeks
Title
Plasma pharmacokinetics of VAY736: The terminal elimination half-life (T1/2)
Description
In Part 3: After the first and last s.c. doses, the terminal elimination half-life (T1/2) will be determined
Time Frame
27 weeks
Title
Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
Description
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.
Time Frame
27 weeks
Title
Plasma pharmacokinetics of VAY736: concentration of VAY736 during the treatment period, before each dose (Ctrough)
Description
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
Time Frame
27 weeks
Title
Safety and tolerability as measured by the percentage of patients wth adverse events
Description
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.
Time Frame
27-188 weeks
Secondary Outcome Measure Information:
Title
pharmacodynamics of VAY736
Description
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
Title
Immunogenicity of VAY736
Description
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
Title
Plasma bioavailability of VAY736: The ratio of area under curve (AUC) for repeated s.c doses and for intravenous dose
Description
Part 3 The ratio of area under curve (AUC) for repeated s.c doses and for intravenous dose is determined
Time Frame
27 weeks
Title
Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
Description
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
Title
Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
Description
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
Title
Plasma pharmacokinetics of VAY736: Observed maximum plasma concentration following drug Administration (Cmax)
Description
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
Title
Plasma pharmacokinetics of VAY736: Time to reach the maximum concentration after drug administration (Tmax)
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17297
Description
Results for CVAY736X2101 from the Novartis Clinical Trials Website
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=422
Description
A Plain Language Trial Summary is available on novartisclinicatrials.com

Learn more about this trial

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

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