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

A Randomized, Two-period Crossover Study to Demonstrate the Comparability of Pharmacokinetics of Subcutaneous Ianalumab Between 2mL Auto-injector/2mL Pre-filled Syringe With 1 mL Pre-filled Syringe in Adult Participants With Autoimmune Disease

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Rheumatoid Arthritis; Systemic Lupus Erythematosus; Sjögrens Disease
• Intervention / Treatment: Biological: VAY736 1ml PFS; Biological: VAY736 2ml AI; Biological: VAY736 2 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.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion criteria:

• Signed informed consent must be obtained before any assessment is performed.
• Male and female patients aged 18 years to 70 years (inclusive).
• Body weight at least 35 kg and not more than 150 kg and must have a body mass index (BMI) within the range of 18 - 35 kg/m2. BMI = Body weight (kg) / [Height (m)]2 at screening.
• Diagnosed with RA, SjD and/or SLE as determined by the investigator.
• Have active disease (RA, SjD or SLE) that may benefit from B-cell depletion therapy, as determined by the investigator.
• Participants currently receiving protocol-allowed SoC should be on stable doses of SoC medications for 4 weeks prior to first dosing of study treatment.
• Ability to communicate well with the investigator, understand and agree to comply with the requirements of the study.

Key Exclusion criteria:

• Use of prohibited therapies.
• Active viral, bacterial or other infections requiring systemic treatment at the time of screening or baseline or history of recurrent clinically significant infection.
• Plans for administration of live vaccines during the study period.
• Uncontrolled co-existing serious disease.
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, refusing or unable to use highly effective methods of contraception while on study treatment and for 6 months after stopping of study drug.
• US (and other countries, if locally required): sexually active males unless using barrier protection during intercourse with women of child-bearing potential while taking study treatment.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Sequence 1 + Thigh; 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	Biological: VAY736 1ml PFS; Solution for injection.; Other Names: Ianalumab; Biological: VAY736 2ml AI; Solution for injection.; Other Names: Ianalumab
Experimental: Cohort 1: Sequence 1 + Abdomen; Patients randomized to receive injection; X 2 mL) AI in TP1 in Abdomen; x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) AI in ETP in Thigh/ Abdomen	Biological: VAY736 1ml PFS; Solution for injection.; Other Names: Ianalumab; Biological: VAY736 2ml AI; Solution for injection.; Other Names: Ianalumab
Experimental: Cohort 1: Sequence 2 + Thigh; 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	Biological: VAY736 1ml PFS; Solution for injection.; Other Names: Ianalumab; Biological: VAY736 2ml AI; Solution for injection.; Other Names: Ianalumab
Experimental: Cohort 1: Sequence 2 + Abdomen; Patients randomized to receive injection; X 2 mL) AI in TP1 in Abdomen; x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) AI in ETP in Thigh/ Abdomen	Biological: VAY736 1ml PFS; Solution for injection.; Other Names: Ianalumab; Biological: VAY736 2ml AI; Solution for injection.; Other Names: Ianalumab
Experimental: Cohort 2: Sequence 1 + Thigh; 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	Biological: VAY736 1ml PFS; Solution for injection.; Other Names: Ianalumab; Biological: VAY736 2 ml PFS; Solution for injection; Other Names: Ianalumab
Experimental: Cohort 2: Sequence 1 + Abdomen; Patients randomized to receive injection; X 2 mL) PFS in TP1 in Abdomen; x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm	Biological: VAY736 1ml PFS; Solution for injection.; Other Names: Ianalumab; Biological: VAY736 2 ml PFS; Solution for injection; Other Names: Ianalumab
Experimental: Cohort 2: Sequence 1 + Upper Arm; 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	Biological: VAY736 1ml PFS; Solution for injection.; Other Names: Ianalumab; Biological: VAY736 2 ml PFS; Solution for injection; Other Names: Ianalumab
Experimental: Cohort 2: Sequence 2 + Thigh; Patients randomized to receive injection; X 2 mL) PFS in TP1 in Thigh; x 1 mL) PFS in TP2 in Thigh (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm	Biological: VAY736 1ml PFS; Solution for injection.; Other Names: Ianalumab; Biological: VAY736 2 ml PFS; Solution for injection; Other Names: Ianalumab
Experimental: Cohort 2: Sequence 2 + Abdomen; 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	Biological: VAY736 1ml PFS; Solution for injection.; Other Names: Ianalumab; Biological: VAY736 2 ml PFS; Solution for injection; Other Names: Ianalumab
Experimental: Cohort 2: Sequence 2 + Upper Arm; Patients randomized to receive injection; X 2 mL) PFS in TP1 in Upper Arm; x 1 mL) PFS in TP2 in Upper Arm (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm	Biological: VAY736 1ml PFS; Solution for injection.; Other Names: Ianalumab; Biological: VAY736 2 ml PFS; Solution for injection; Other Names: Ianalumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1: Area under the curve (AUC) calculated to the end of a dosing interval (tau) at steady-state (AUCtau) for ianalumab	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	Over a dosing interval after 3rd (between Week 8 and 12) and 6th dose (between Week 20 and 24).
Cohort 1: Maximum (peak) observed serum drug concentration after dose administration (Cmax) for ianalumab	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	Over a dosing interval after 3rd (between Week 8 and 12) and 6th dose (between Week 20 and 24).
Cohort 2 (optional): Area under the curve (AUC) calculated to the end of a dosing interval (tau) at steady-state (AUCtau) for ianalumab	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.	Over a dosing interval after 3rd (between Week 8 and 12) and 6th dose (between Week 20 and 24).
Cohort 2 (optional): Maximum (peak) observed serum drug concentration after dose administration (Cmax) for ianalumab	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.	Over a dosing interval after 3rd (between Week 8 and 12) and 6th dose (between Week 20 and 24).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1: Time to reach maximum (peak) serum drug concentration following dose administration (Tmax) for ianalumab	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	After the 3rd and 6th dose
Cohort 2 (optional): Time to reach maximum (peak) serum drug concentration following dose administration (Tmax) for ianalumab	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	After the 3rd and 6th dose
Cohort 1: Concentration at the end of a dosing interval (Ctrough) for ianalumab	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	At the end of dosing interval
Cohort 2 (optional): Concentration at the end of a dosing interval (Ctrough) for ianalumab	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	At the end of dosing interval
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)	To evaluate the safety and tolerability of ianalumab administered 300 mg s.c. monthly.	From date of randomization until 30 days safety follow-up, assessed up to approximately 56 months
Anti-ianalumab antibodies (ADA)	To assess the immunogenicity of ianalumab administered 300 mg s.c. monthly	From date of randomization until 30 days safety follow-up, assessed up to approximately 56 months
Incidence of ADA positive participants	To assess the immunogenicity of ianalumab administered 300 mg s.c. monthly	From date of randomization until 30 days safety follow-up, assessed up to approximately 56 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): June 26, 2024
• Primary Completion (Estimated): July 29, 2025
• Study Completion (Estimated): February 8, 2029

Study Registration Dates

• First Submitted: February 28, 2024
• First Submitted That Met QC Criteria: February 28, 2024
• First Posted (Actual): March 5, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: VAY736; B cell depletion; Rheumatoid Arthritis (RA); Cmax; ianalumab; Systemic lupus erythematosus (SLE); Area under the curve (AUC); Sjögrens Disease (SjD); Pharmacokinetic (PK) comparability; 2 mL auto-injector (AI); 1 mL pre-filled syringe (PFS); 2 mL pre-filled syringe (PFS)
• Additional Relevant MeSH Terms: Immune System Diseases; Eye Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Arthritis; Arthritis, Rheumatoid; Lupus Erythematosus, Systemic; Autoimmune Diseases; Sjogren's Syndrome
• Other Study ID Numbers: CVAY736A2202; 2023-508996-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No