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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02675803
• Collaborator: (none)
• Enrollment: 65
• Location: 1
• Arms: 2
• Actual Duration (Months): 85.1
• Patients Per Site Per Month: 0.8

Study Details

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.

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.

Study Design

• Study Type: Interventional
• 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: Dec 20, 2010
• Actual Primary Completion Date: Jan 22, 2018
• Actual Study Completion Date: Jan 22, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VAY736 VAY736 active	Biological: VAY736; VAY736 treatment
Placebo Comparator: Placebo VAY736 placebo	Biological: VAY736 placebo; VAY736 placebo

Outcome Measures

Primary Outcome Measures

1. Safety and tolerability as measured by the number of patients wth adverse events [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 [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) [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) [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) [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) [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) [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) [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) [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 [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 [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 [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 [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) [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) [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) [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) [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Berlin		Germany	10117

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02675803
• Other Study ID Numbers: CVAY736X2101; 2010-020156-65
• First Posted: Feb 5, 2016
• Last Update Posted: Dec 11, 2020
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Novartis Pharmaceuticals: Rheumatoid arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

No Results Posted as of Dec 11, 2020