Clinical trial NCT06293365: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Sjögrens Disease
Systemic Lupus Erythematosus
Rheumatoid Arthritis
Keywords: Sjögrens Disease (SjD)
Systemic lupus erythematosus (SLE)
Rheumatoid Arthritis (RA)
Pharmacokinetic (PK) comparability
2 mL auto-injector (AI)
1 mL pre-filled syringe (PFS)
2 mL pre-filled syringe (PFS)
VAY736
ianalumab
B cell depletion
Area under the curve (AUC)
Cmax
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-03-05
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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 cohort will 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:

  * 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 x 1 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cohort 1: Area under the curve (AUC) calculated to the end of a dosing interval (tau) at steady-state (AUCtau) for ianalumab
timeFrame: Over a dosing interval after 3rd (between Week 8 and 12) and 6th dose (between Week 20 and 24).
measure: Cohort 1: Maximum (peak) observed serum drug concentration after dose administration (Cmax) for ianalumab
timeFrame: Over a dosing interval after 3rd (between Week 8 and 12) and 6th dose (between Week 20 and 24).
measure: Cohort 2: Area under the curve (AUC) calculated to the end of a dosing interval (tau) at steady-state (AUCtau) for ianalumab
timeFrame: Over a dosing interval after 3rd (between Week 8 and 12) and 6th dose (between Week 20 and 24).
measure: Cohort 2: Maximum (peak) observed serum drug concentration after dose administration (Cmax) for ianalumab
timeFrame: Over a dosing interval after 3rd (between Week 8 and 12) and 6th dose (between Week 20 and 24).
Secondary outcomes:
measure: Cohort 1: Time to reach maximum (peak) serum drug concentration following dose administration (Tmax) for ianalumab
timeFrame: After the 3rd and 6th dose
measure: Cohort 2: Time to reach maximum (peak) serum drug concentration following dose administration (Tmax) for ianalumab
timeFrame: After the 3rd and 6th dose
measure: Cohort 1: Concentration at the end of a dosing interval (Ctrough) for ianalumab
timeFrame: At the end of dosing interval
measure: Cohort 2: Concentration at the end of a dosing interval (Ctrough) for ianalumab
timeFrame: At the end of dosing interval
measure: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From date of randomization until 30 days safety follow-up, assessed up to approximately 56 months
measure: Anti-ianalumab antibodies (ADA)
timeFrame: From date of randomization until 30 days safety follow-up, assessed up to approximately 56 months
measure: Incidence of ADA positive participants
timeFrame: From date of randomization until 30 days safety follow-up, assessed up to approximately 56 months
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group Llc
state: Alabama
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: La Palma
country: United States
facility: Advanced Medical Research
state: California
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Lawrenceville
country: United States
facility: Parris and Associates Rheumatology
state: Georgia
city: Indianapolis
country: United States
facility: Indiana Univ School of Dentistry
state: Indiana
city: Baton Rouge
country: United States
facility: Ochsner Health System
state: Louisiana
city: Grand Blanc
country: United States
facility: Ahmed Arif Medical Research Center
state: Michigan
city: Middleburg Heights
country: United States
facility: Paramount Med Rsrch and Consult LLC
state: Ohio
city: Oklahoma City
country: United States
facility: RAO Research LLS
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clin Res
state: Pennsylvania
city: Jackson
country: United States
facility: West Tennessee Research Institute
state: Tennessee
city: Memphis
country: United States
facility: Shelby Research LLC
state: Tennessee
city: Bellaire
country: United States
facility: Novel Research LLC
state: Texas
city: Mesquite
country: United States
facility: Southwest Rheum Rsrch LLC
state: Texas
city: San Antonio
country: United States
facility: Uni of Texas Health Science Center
state: Texas
city: Spring
country: United States
facility: Advanced Rheumatology of Houston
state: Texas
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Tucuman
country: Argentina
facility: Novartis Investigative Site
state: San Miguel De Tucuman
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Rimouski
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Trois Rivieres
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Praha 2
country: Czechia
facility: Novartis Investigative Site
city: Uherske Hradiste
country: Czechia
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Salerno
country: Italy
facility: Novartis Investigative Site
state: SA
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Santiago De Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: