Two-period Crossover Study to Demonstrate the Comparability of Pharmacokinetics of Subcutaneous Ianalumab Between 2mL Auto-injector/2mL PFS with1mL Pre-filled Syringe in Adult Participants With Autoimmune Disease
- Conditions
- Systemic Lupus ErythematosusSjögrens DiseaseRheumatoid Arthritis
- Interventions
- Biological: VAY736 1ml PFSBiological: VAY736 2ml AIBiological: VAY736 2 ml PFS
- Registration Number
- NCT06293365
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of this study is to demonstrate the comparability of ianalumab exposure following the sub-cutaneous (s.c.) administration of one injection of 300 mg/2 mL auto-injector (AI) versus two injections of 150 mg/1 mL pre-filled syringe (PFS), and to evaluate the safety and tolerability of ianalumab following the s.c. administration of both devices in participants with rheumatoid arthritis (RA), Sjögren's disease (SjD), or systemic lupus erythematosus (SLE).
A second optional cohort may be included with the objective of demonstrating the comparability of pharmacokinetics of ianalumab between 1 x 2 mL Pre-filled Syringe (PFS) and 2 x 1 mL PFS.
- Detailed Description
The study consists of the following periods:
Screening period (up to 4 weeks):
Following the signing of the informed consent, participants will be assessed for eligibility during this period of up to 4 weeks.
Treatment Period 1 + Treatment Period 2, (Week 0 to Week 24):
After completion of the screening period, eligible participants will be randomized at the Baseline visit (Week 0) to one of the 2 treatment sequences (treatment switch at Week 12) in a ratio of 1:1 described below:
* Cohort 1:
* Sequence 1: ianalumab 300 mg s.c. (2 x 1 mL PFS) monthly + SoC in Treatment Period 1 and ianalumab 300 mg s.c. (1 x 2 mL AI) monthly + SoC in Treatment Period 2
* Sequence 2: ianalumab 300 mg s.c. (1 x 2 mL AI) monthly + SoC in Treatment Period 1 and ianalumab 300 mg s.c. (2 x 1 mL PFS) monthly + SoC in Treatment Period 2
* Cohort 2 (Optional):
* Sequence 1: ianalumab 300 mg s.c. (2 x 1 mL PFS) monthly + SoC in Treatment Period 1 and ianalumab 300 mg s.c. (1 x 2 mL PFS) monthly + SoC in Treatment Period 2
* Sequence 2: ianalumab 300 mg s.c. (1 x 2 mL PFS) monthly + SoC in Treatment Period 1 and ianalumab 300 mg s.c. (2 x 1 mL PFS) monthly + SoC in Treatment Period 2 In addition, within each sequence, participants will be further randomized to one of the predetermined injection sites with equal allocation, resulting in a total randomization combination of four (2 sequences x 2 injection sites) for Cohort 1 and six (2 sequences x 3 injection sites) for Cohort 2, respectively.
Extended Treatment period (Week 24 to Week 72): After completion of Week 24 assessment, all participants (who did not discontinue during treatment period) will have the option to enter the extended treatment period to receive ianalumab 300 mg s.c. (Cohort 1: 2 mL AI; Cohort 2: 2 mL PFS) monthly up to Week 68. The end of treatment (EOT) visit will be performed 4 weeks after the last study treatment administration, i.e., at Week 72.
Mandatory Post-Treatment safety follow-up period (from Week 72 to Week 88): Participants who completed the last study treatment or prematurely discontinued from study treatment will enter the post-treatment safety follow-up period.
Conditional Post-Treatment safety follow-up period (from Week 88 to Week 176) Post-treatment follow-up will be performed until B-cell recovery or up to 2 years. B-cell recovery is defined when CD19+ B-cell counts return to \>= 50 cells/μL or \>= 80% of baseline value, whichever occurs earlier.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 140
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Cohort 2: Sequence 1 + Upper Arm VAY736 1ml PFS Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Upper Arm (1 X 2 mL) PFS in TP2 in Upper Arm (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm Cohort 1: Sequence 1 + Thigh VAY736 1ml PFS Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Thigh (1 X 2 mL) AI in TP2 in Thigh (1 x 2 mL) AI in ETP in Thigh/ Abdomen Cohort 1: Sequence 2 + Abdomen VAY736 2ml AI Patients randomized to receive injection 1. X 2 mL) AI in TP1 in Abdomen 2. x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) AI in ETP in Thigh/ Abdomen Cohort 2: Sequence 2 + Thigh VAY736 2 ml PFS Patients randomized to receive injection 1. X 2 mL) PFS in TP1 in Thigh 2. x 1 mL) PFS in TP2 in Thigh (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm Cohort 2: Sequence 2 + Upper Arm VAY736 2 ml PFS Patients randomized to receive injection 1. X 2 mL) PFS in TP1 in Upper Arm 2. x 1 mL) PFS in TP2 in Upper Arm (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm Cohort 2: Sequence 1 + Upper Arm VAY736 2 ml PFS Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Upper Arm (1 X 2 mL) PFS in TP2 in Upper Arm (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm Cohort 1: Sequence 1 + Thigh VAY736 2ml AI Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Thigh (1 X 2 mL) AI in TP2 in Thigh (1 x 2 mL) AI in ETP in Thigh/ Abdomen Cohort 1: Sequence 2 + Thigh VAY736 1ml PFS Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Thigh (1 X 2 mL) AI in TP2 in Thigh (1 x 2 mL) AI in ETP in Thigh/ Abdomen Cohort 1: Sequence 2 + Abdomen VAY736 1ml PFS Patients randomized to receive injection 1. X 2 mL) AI in TP1 in Abdomen 2. x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) AI in ETP in Thigh/ Abdomen Cohort 2: Sequence 1 + Thigh VAY736 2 ml PFS Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Thigh (1 X 2 mL) PFS in TP2 in Thigh (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm Cohort 1: Sequence 1 + Abdomen VAY736 1ml PFS Patients randomized to receive injection 1. X 2 mL) AI in TP1 in Abdomen 2. x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) AI in ETP in Thigh/ Abdomen Cohort 1: Sequence 1 + Abdomen VAY736 2ml AI Patients randomized to receive injection 1. X 2 mL) AI in TP1 in Abdomen 2. x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) AI in ETP in Thigh/ Abdomen Cohort 1: Sequence 2 + Thigh VAY736 2ml AI Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Thigh (1 X 2 mL) AI in TP2 in Thigh (1 x 2 mL) AI in ETP in Thigh/ Abdomen Cohort 2: Sequence 1 + Thigh VAY736 1ml PFS Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Thigh (1 X 2 mL) PFS in TP2 in Thigh (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm Cohort 2: Sequence 1 + Abdomen VAY736 1ml PFS Patients randomized to receive injection 1. X 2 mL) PFS in TP1 in Abdomen 2. x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm Cohort 2: Sequence 1 + Abdomen VAY736 2 ml PFS Patients randomized to receive injection 1. X 2 mL) PFS in TP1 in Abdomen 2. x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm Cohort 2: Sequence 2 + Thigh VAY736 1ml PFS Patients randomized to receive injection 1. X 2 mL) PFS in TP1 in Thigh 2. x 1 mL) PFS in TP2 in Thigh (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm Cohort 2: Sequence 2 + Abdomen VAY736 1ml PFS Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Abdomen (1 X 2 mL) PFS in TP2 in Abdomen (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm Cohort 2: Sequence 2 + Abdomen VAY736 2 ml PFS Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Abdomen (1 X 2 mL) PFS in TP2 in Abdomen (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm Cohort 2: Sequence 2 + Upper Arm VAY736 1ml PFS Patients randomized to receive injection 1. X 2 mL) PFS in TP1 in Upper Arm 2. x 1 mL) PFS in TP2 in Upper Arm (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm
- Primary Outcome Measures
Name Time Method Cohort 1: Area under the curve (AUC) calculated to the end of a dosing interval (tau) at steady-state (AUCtau) for ianalumab Over a dosing interval after 3rd (between Week 8 and 12) and 6th dose (between Week 20 and 24). To demonstrate the pharmacokinetics (PK) comparability of ianalumab 300 mg s.c. at steady state between the 1 x 2 mL AI and 2 x 1 mL PFS
Cohort 2 (optional): Area under the curve (AUC) calculated to the end of a dosing interval (tau) at steady-state (AUCtau) for ianalumab Over a dosing interval after 3rd (between Week 8 and 12) and 6th dose (between Week 20 and 24). To demonstrate the pharmacokinetics (PK) comparability of ianalumab 300 mg s.c. at steady state between the 1 x 2 mL PFS and 2 x 1 mL PFS.
Cohort 2 (optional): Maximum (peak) observed serum drug concentration after dose administration (Cmax) for ianalumab Over a dosing interval after 3rd (between Week 8 and 12) and 6th dose (between Week 20 and 24). To demonstrate the pharmacokinetics (PK) comparability of ianalumab 300 mg s.c. at steady state between the 1 x 2 mL PFS and 2 x 1 mL PFS.
Cohort 1: Maximum (peak) observed serum drug concentration after dose administration (Cmax) for ianalumab Over a dosing interval after 3rd (between Week 8 and 12) and 6th dose (between Week 20 and 24). To demonstrate the pharmacokinetics (PK) comparability of ianalumab 300 mg s.c. at steady state between the 1 x 2 mL AI and 2 x 1 mL PFS
- Secondary Outcome Measures
Name Time Method Cohort 1: Time to reach maximum (peak) serum drug concentration following dose administration (Tmax) for ianalumab After the 3rd and 6th dose To evaluate the pharmacokinetics of ianalumab 300 mg s.c. at steady state under the 1 x 2 mL AI and 2 x 1 mL PFS
Cohort 2 (optional): Time to reach maximum (peak) serum drug concentration following dose administration (Tmax) for ianalumab After the 3rd and 6th dose To evaluate the pharmacokinetics of ianalumab 300 mg s.c. at steady state under the 1 x 2 mL PFS and 2 x 1 mL PFS
Cohort 1: Concentration at the end of a dosing interval (Ctrough) for ianalumab At the end of dosing interval To evaluate the pharmacokinetics of ianalumab 300 mg s.c. at steady state under the 1 x 2 mL AI and 2 x 1 mL PFS
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) From date of randomization until 30 days safety follow-up, assessed up to approximately 56 months To evaluate the safety and tolerability of ianalumab administered 300 mg s.c. monthly.
Anti-ianalumab antibodies (ADA) From date of randomization until 30 days safety follow-up, assessed up to approximately 56 months To assess the immunogenicity of ianalumab administered 300 mg s.c. monthly
Incidence of ADA positive participants From date of randomization until 30 days safety follow-up, assessed up to approximately 56 months To assess the immunogenicity of ianalumab administered 300 mg s.c. monthly
Cohort 2 (optional): Concentration at the end of a dosing interval (Ctrough) for ianalumab At the end of dosing interval To evaluate the pharmacokinetics of ianalumab 300 mg s.c. at steady state under the 1 x 2 mL PFS and 2 x 1 mL PFS
Trial Locations
- Locations (18)
Pinnacle Research Group Llc
🇺🇸Anniston, Alabama, United States
Providence Medical Foundation
🇺🇸Fullerton, California, United States
Advanced Medical Research
🇺🇸La Palma, California, United States
Conquest Research
🇺🇸Winter Park, Florida, United States
Parris and Associates Rheumatology
🇺🇸Lawrenceville, Georgia, United States
Indiana Univ School of Dentistry
🇺🇸Indianapolis, Indiana, United States
Ochsner Health System
🇺🇸Baton Rouge, Louisiana, United States
Ahmed Arif Medical Research Center
🇺🇸Grand Blanc, Michigan, United States
Paramount Med Rsrch and Consult LLC
🇺🇸Middleburg Heights, Ohio, United States
RAO Research LLS
🇺🇸Oklahoma City, Oklahoma, United States
Altoona Center for Clin Res
🇺🇸Duncansville, Pennsylvania, United States
West Tennessee Research Institute
🇺🇸Jackson, Tennessee, United States
Shelby Research LLC
🇺🇸Memphis, Tennessee, United States
Novel Research LLC
🇺🇸Bellaire, Texas, United States
Southwest Rheum Rsrch LLC
🇺🇸Mesquite, Texas, United States
Uni of Texas Health Science Center
🇺🇸San Antonio, Texas, United States
Advanced Rheumatology of Houston
🇺🇸Spring, Texas, United States
Novartis Investigative Site
🇪🇸Madrid, Spain