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

NCT02675803 | Completed Phase 1

• 2 other identifiers: CVAY736X21012010-020156-65
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis

Outcome Measures

Primary Outcomes (10)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (7)

• pharmacodynamics of VAY736

  27-188 weeks

• Immunogenicity of VAY736

  27-188 weeks

• Plasma bioavailability of VAY736: The ratio of area under curve (AUC) for repeated s.c doses and for intravenous dose

  27 weeks

• Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)

  34-188 weeks

• Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)

  34-188 weeks

Study Arms (2)

VAY736

EXPERIMENTAL

VAY736 active

Biological: VAY736

Placebo

PLACEBO COMPARATOR

VAY736 placebo

Biological: VAY736 placebo

Interventions

VAY736 BIOLOGICAL

VAY736 treatment

VAY736

VAY736 placebo BIOLOGICAL

VAY736 placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Berlin, 10117, Germany

Location

Related Links

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

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

ianalumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2015
• First Posted: February 5, 2016
• Study Start: December 20, 2010
• Primary Completion: January 22, 2018
• Study Completion: January 22, 2018
• Last Updated: December 11, 2020

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)