Study Comparing Two VAY736 Drug Products in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This study will assess the safety and pharmacokinetic comparability of two VAY736 drug products in patients with rheumatoid arthritis.

Official Title
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A Randomized, Open Label, Multiple Dose, Parallel Group Study to Assess the Safety and Pharmacokinetic Comparability of Two VAY736 Drug Products in Patients With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: ianalumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfill 2010 ACR/EULAR criteria for RA Aletaha et al 2010 at Screening Active disease defined as ≥ 2 swollen joints (of 58 evaluable joints) and ≥ 2 tender joints (of 60 evaluable joints) despite stable MTX ≤ 25 mg/week and/or hydroxychloroquine ≤ 400 mg/day treatment for at least 2 months prior to randomization Exclusion Criteria: Prior or previous use of (specific dosages and intervals prior to study start may apply): other investigational drugs, B-cell depleting therapy (e.g. rituximab), monoclonal antibodies (mAb), i.v. / s.c. Ig, thymoglobulin, i.v. or oral cyclophosphamide, oral cyclosporine, soluble cytokine receptors, azathioprine. Currently receiving prednisone >10 mg/day (or equivalent oral glucocorticoid) or dose adjustment within 2 weeks prior to randomization Active viral, bacterial or other infections requiring systemic treatment at the time of screening or enrollment, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms Receipt of live/attenuated vaccine within a 2-month period before randomization Pregnant or nursing (lactating) women Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception from screening and for 4 months after stopping of investigational drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Reference VAY736 Drug Product<br>Powder for solution for injection / infusion | Biological: ianalumab<br>* Human monoclonal antibody (mAb) of type IgG1/κ binding to B-cell activating-receptor (BAFF-R)<br>* Other names: VAY736;|
| Experimental: Test VAY736 Drug Product<br>Solution for injection | Biological: ianalumab<br>* Human monoclonal antibody (mAb) of type IgG1/κ binding to B-cell activating-receptor (BAFF-R)<br>* Other names: VAY736;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as measured by the number of patients with adverse events | The number of patients with adverse events after repeated subcutaneous (s.c) injections of a fixed dose of ianalumab | Week 0 - 112 | 
| Pharmacokinetic comparability at steady state - AUCtau | The area under the serum ianalumab concentration-time curve from time zero to the end of the dosing interval (AUCtau) | Week 8 - 12 | 
| Pharmacokinetic comparability at steady state - Cmax | Observed maximum serum concentration of ianalumab following drug administration (Cmax) | Week 8 - 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic comparability after the first dose - AUCtau | The area under the serum ianalumab concentration-time curve from time zero to the end of the dosing interval (AUCtau) | Week 0 - 4 | 
| Pharmacokinetic comparability after the first dose - Cmax | Observed maximum serum concentration of ianalumab following drug administration (Cmax) | Week 0 - 4 | 
| Pharmacokinetic comparability after the first dose - Tmax | Time to reach the maximum concentration after drug administration (Tmax) | Week 0 - 4 | 
| Pharmacokinetic comparability of two ianalumab drug products after the last dose - AUCinf | The area under the serum ianalumab concentration-time curve from time zero to infinity (AUCinf) | Week 8 - 12 | 
| Pharmacokinetic comparability after the last dose - Tmax | Time to reach the maximum concentration after drug administration (Tmax) | Week 8 - 12 | 
| Pharmacokinetic comparability after the last dose - T1/2 | The terminal elimination half-life (T1/2) | Week 8 - 12 | 
| Pharmacokinetic comparability at the end of each dosing interval - Ctrough | Observed minimum serum ianalumab concentration following drug administration (Ctrough) | Week 0 - 12 | 
| Pharmacodynamic effect as measured by B-cell level | Circulating B cells (CD19+) | Week 0 - 112 | 
| Immunogenicity as measured by Anti-Drug Antibodies | Anti-ianalumab antibodies (ADA); incidence of ADA positive patients and correlation with AEs, PK and clinical outcomes | Week 0 - 112 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, VAY736, Ianalumab