Clinical trial NCT06581198: A Study of Rapcabtagene Autoleucel in Systemic Lupus Erythematosus (SLE) Patients With Active, Refractory Lupus Nephritis (LN)
Official title: A Phase 2, Adaptive, Randomized, Open-label, Assessor-blinded Active-controlled Study to Evaluate the Efficacy and Safety of Rapcabtagene Autoleucel Versus Standard of Care in Patients Suffering From Systemic Lupus Erythematosus (SLE) With Active, Refractory Lupus Nephritis (LN).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lupus Erythematosus, Systemic
Lupus Nephritis
Keywords: Chimeric Antigen Receptor-T (CAR-T)
rapcabtagene autoleucel
Lupus Nephritis (LN)
Systemic Lupus Erythematosus (SLE)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-09-03
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of rapcabtagene autoleucel (administered once following lymphodepletion) versus Standard of Care (SOC) in patients with systemic lupus erythematosus (SLE) with active, refractory lupus nephritis (LN).

Detailed description: This is a Phase 2, adaptive, five-year, randomized, assessor-blinded, active controlled study:

* Part A: Participants suffering from systemic lupus erythematosus (SLE) with active, refractory LN will be randomized to Regimen 1, Regimen 2, or SOC.
* Part B: Participants suffering from SLE with active, refractory LN will be randomized to the selected regimen from Part A or SOC.

The study will consist of two periods:

* A screening period lasting up to 6 weeks, and
* A randomized treatment period and primary follow-up period lasting up to 5 years.

Participants in the SoC arm whose signs and symptoms are not fully controlled may receive rapcabtagene autoleucel treatment once the participant is confirmed to be eligible.

Eligibility criteria: Key Inclusion Criteria:

* Men and women with SLE, aged \>= 18 years and =\< 65 years at screening, fulfilling the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE at screening.
* Participant must be positive for at least one of the following autoantibodies at screening: antinuclear antibodies (ANA) at a titer of \>= 1:80 (on HEp-2 cells or an equivalent positive test), or anti-dsDNA (above the ULN); or anti-Sm (above the ULN) as determined by a central laboratory.
* Active lupus nephritis without signs of significant chronicity
* SLEDAI-2K Criteria at screening: SLEDAI-2K score \>= 6 points (Gladman et al 2002, Touma et al 2011), excluding points attributed to "fever", "lupus headache", "alopecia", and "organic brain syndrome".
* Inadequate response at screening to at least two LN treatment regimens

Key Exclusion Criteria:

* Any acute, severe lupus related-flare at screening that needs immediate treatment other than pulse GCs and/or makes the immunosuppressive washout impossible and, thus, makes the participant ineligible for CD19 CAR-T therapy
* Inadequate organ function during screening and prior to randomization
* History or current diagnosis of ECG or cardiac abnormalities indicating significant risk of safety for participants prior to randomization
* Human immunodeficiency virus (HIV) positivity at screening.
* Acute or chronic infection with hepatitis B (HBV) or hepatitis C (HCV) at screening.
* Evidence of active or latent tuberculosis.
* Grade 2 or higher thromboembolic event in the past 4 weeks prior to screening.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Part A and Part B: Percentage of participants achieving clinical response at Week 52.
timeFrame: Week 52
Secondary outcomes:
measure: Part A and Part B: Percentage of participants achieving complete renal response (CRR) at Week 52
timeFrame: Week 52
measure: Part A and Part B: Number of weeks where Lupus Low Disease Activity Score (LLDAS) was achieved from Week 12 until Week 52
timeFrame: Week 12 to Week 52
measure: Part A and Part B: Percentage of participants without flaring (i.e., 1 new BILAG2004 A or 2 new BILAG2004 B flares) from Week 12 through Week 52
timeFrame: Week 12 to Week 52
measure: Part A and Part B: Annualized cumulative corticosteroids dose until Week 52
timeFrame: Week 52
measure: Part A and Part B: Percentage of participants who are negative (i.e., titer within normal limits) for antinuclear antibodies (ANA), anti-dsDNA, and anti-Sm at Week 52
timeFrame: Week 52
measure: Part A and Part B: FACIT-Fatigue score change from baseline at Week 52
timeFrame: Baseline to Week 52
measure: Part A and Part B: Percentage of participants who were in Sustained Remission at Week 52 to Week 76
timeFrame: Week 52 to Week 76
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF
state: California
city: San Pablo
country: United States
facility: Sutter Health Network
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Iowa City
country: United States
facility: University Of Iowa
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Olomouc
country: Czechia
facility: Novartis Investigative Site
city: Praha 2
country: Czechia
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Vandoeuvre Les Nancy
country: France
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
state: Sachsen
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Kobe
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Kanazawa
country: Japan
facility: Novartis Investigative Site
state: Ishikawa
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Sendai city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Suita
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Izumo-city
country: Japan
facility: Novartis Investigative Site
state: Shimane
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chiba
country: Japan
facility: Novartis Investigative Site
city: Kyoto
country: Japan
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Santander
country: Spain
facility: Novartis Investigative Site
state: Cantabria
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Santiago De Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: