A clinical study aimed at learning more about the effects of YTB323 in people with active difficult-to-treat kidney disease due to systemic lupus erythematosus (SLE)
Zusammenfassung der Studie
The goal of this trial is to learn more about the effects of YTB323 compared to standard treatment in people with active difficult-to-treat kidney disease caused by systemic lupus erythematosus (SLE). SLE is the most common type of lupus. Lupus is an autoimmune disease in which a person's immune system attacks its own tissues and organs. This can lead to inflammation and damage in various organs. Kidney damage due to inflammation (lupus nephritis, LN) is a common complication of SLE. This can prevent the kidneys from functioning properly and cause permanent damage. The effect of YTB323 on SLE/LN is being examined. This is a type of treatment called chimeric antigen receptor T-cell therapy (CAR-T). CAR-T cell therapy involves collecting a person's T cells and modifying them in the lab to identify and destroy B immune cells that are important for the development of lupus. The modified T cells from participants are then reintroduced into the person's body. Before administering YTB323-CAR-T cell therapy, individuals often receive conditioning treatment to reduce the number of blood cells called lymphocytes and improve the likelihood that this YTB323-CAR-T cell therapy will work. The conditioning treatment used in this study includes two chemotherapy drugs, fludarabine and cyclophosphamide. This conditioning treatment will make room in the body for the modified YTB323-CAR-T cells of the participant.
(BASEC)
Untersuchte Intervention
The following interventions are proposed to participants in Parts A and B:
Part A: Participants are randomly assigned to one of 3 groups via a computer program. Participants are assigned twice as often to groups 1 or 2 as to group 3.
• Group 1: Participants with systemic lupus erythematosus (SLE) with active and refractory LN are randomized to regimen 1, regimen 2, or SOC.
• Group 2: Participants with SLE with active and refractory LN are randomly assigned to the selected regimen in Part A or SOC.
• Group 3: Participants receive standard treatment.
Researchers will choose a treatment from Part A to continue the study during Part B of the trial.
Part B: Researchers will randomly assign participants to 1 of 2 groups using a computer program:
• Group 1: Participants will receive an infusion of YTB323 directly into a vein after receiving the selected conditioning treatment.
• Group 2: Participants receive standard treatment.
Researchers, study staff, and participants will know which treatment they are receiving. The physician who will assess the severity of SLE/LN and the effects of the study treatment will not know who is receiving which treatment. Participants are hospitalized to receive the YTB323 infusion. Participants will visit the study center 24 times in the first year and 8 times in the second year. Researchers will monitor participants' SLE/LN and overall health status throughout the study.
(BASEC)
Untersuchte Krankheit(en)
The study population consists of adult men or women (aged 18 to 65 years) with active kidney disease due to systemic lupus erythematosus (SLE).
(BASEC)
1. Men and women with SLE aged at least 18 years and a maximum of 65 years 2. The participant must have at least one of the following autoantibodies at the preliminary examination: antinuclear antibodies (ANA) or anti-DNA; or anti-Sm 3. Active lupus nephritis without signs of significant chronicity (BASEC)
Ausschlusskriterien
1. BMI at the preliminary examination less than or equal to 18.5 or greater than or equal to 35 kg/m2 or more 2. Any acute and severe flare due to lupus at the preliminary examination, requiring immediate treatment, unless the study physician deems it essential and the participant(s) cannot continue to participate in the CD19-CAR-T treatment study 3. Organ function failure at the preliminary examination and before randomization (BASEC)
Studienstandort
Lausanne
(BASEC)
Sponsor
Novartis Pharma Schweiz AG Suurstoffi 14 6343 Rotkreuz Switzerland
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Dr. Juliane Kuehn
+41 79 295 16 80
juliane.kuehn@clutternovartis.comNovartis Pharma Schweiz AG Suurstoffi 14 6343 Rotkreuz Switzerland
(BASEC)
Allgemeine Auskünfte
Novartis Pharmaceuticals
1-888-669-6682
juliane.kuehn@clutternovartis.com(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Waadt
(BASEC)
Datum der Bewilligung durch die Ethikkommission
01.04.2025
(BASEC)
ICTRP Studien-ID
NCT06581198 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
Étude de phase 2, adaptative, randomisée, en ouvert, avec évaluateur en aveugle, contrôlée contre substance active, visant à évaluer l’efficacité et la sécurité d’emploi du rapcabtagène autoleucel par rapport au traitement standard chez des patients atteints de lupus érythémateux disséminé (LED) avec néphropathie lupique (NL) active et réfractaire (BASEC)
Wissenschaftlicher Titel
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). (ICTRP)
Öffentlicher Titel
A Study of Rapcabtagene Autoleucel in Systemic Lupus Erythematosus (SLE) Patients With Active, Refractory Lupus Nephritis (LN) (ICTRP)
Untersuchte Krankheit(en)
Lupus Erythematosus, SystemicLupus Nephritis (ICTRP)
Untersuchte Intervention
Biological: rapcabtagene autoleucel Regimen 1Biological: rapcabtagene autoleucel Regimen 2Other: Standard of Care (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
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. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Part A and Part B: Percentage of participants achieving clinical response at Week 52. (ICTRP)
Part A and Part B: Percentage of participants achieving complete renal response (CRR) at Week 52;Part A and Part B: Number of weeks where Lupus Low Disease Activity Score (LLDAS) was achieved from Week 12 until Week 52;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;Part A and Part B: Annualized cumulative corticosteroids dose until Week 52;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;Part A and Part B: FACIT-Fatigue score change from baseline at Week 52;Part A and Part B: Percentage of participants who were in Sustained Remission at Week 52 to Week 76 (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Novartis PharmaceuticalsNovartis Pharmaceuticals, novartis.email@novartis.com, 1-888-669-6682, Novartis Pharmaceuticals (ICTRP)
Sekundäre IDs
2023-510150-17-00, CYTB323J12201 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT06581198 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar