ANCA Associated Vasculitis (AAV)
Conditions
Keywords
Chimeric Antigen Receptor-T (CAR-T), rapcabtagene autoleucel, anti-neutrophil cytoplasmic antibody (ANCA), ANCA-associated vasculitis/vasculitides (AAV), Granulomatosis with Polyangiitis (GPA), Microscopic Polyangiitis (MPA)
Brief summary
The purpose of this study is to evaluate the efficacy and safety of rapcabtagene autoleucel versus comparator in participants with severe active Granulomatosis with Polyangiitis (GPA) or Microscopic Polyangiitis (MPA)
Detailed description
This is a Phase 2, randomized, assessor-blinded active controlled study. This study comprises two cohorts: * A lead-in cohort enrolling participants to receive rapcabtagene autoleucel * A randomized cohort with participants receiving either rapcabtagene autoleucel or comparator. After end of study (EOS), participants who received rapcabtagene autoleucel infusion will enter a long-term follow-up (LTFU) period lasting up to 15 years after rapcabtagene autoleucel infusion. This LTFU will be described in a separate study protocol.
Interventions
BIOLOGICALRapcabtagene autoleucel
Single infusion of rapcabtagene autoleucel
OTHERActive Comparator
Active comparator option as per protocol
DRUGGlucocorticoids
Concomitant glucocorticoids as per protocol
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The study investigator and the participant will be unblinded to the study treatment. A blinded assessor will perform the efficacy assessments to minimize bias in data collection.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria: 1. Men and women, aged ≥18 and ≤ 75 years with a diagnosis of GPA or MPA according to the American College of Rheumatology/ European League Against Rheumatism 2022 (ACR/EULAR 2022) classification criteria 2. Positive test for ANCA-autoantibodies 3. GPA and MPA participants with severe active disease Key
Exclusion criteria
1. Any condition that could prevent a complete washout of medications or could otherwise make the participant ineligible for anti-CD19 CAR-T therapy and further participation in the study 2. Hypersensitivity and/or contraindications to any product to be given to the participant as part of the study protocol 3. Other systemic autoimmune diseases requiring therapy 4. Any medical conditions that are not related to GPA/MPA that would jeopardize the ability of the participant to tolerate CD19 CAR-T cell therapy 5. Inadequate organ function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival (EFS) | From randomization until the occurrence of an EFS event, up to approx. 4 years after randomization | Event-free survival (EFS) defined as the time from Randomization to the first occurrence of as per protocol defined events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients achieving complete remission | Up to Week 13 | Complete remission is defined by Birmingham Vasculitis Activity Score version 3 (BVASv3) |
| Adjusted annual cumulative GC dose between Randomization and analysis cutoff date | From randomization until the occurrence of an EFS event, up to approx. 4 years after randomization | The adjusted annual cumulative glucocorticoid dose refers to the total amount of glucocorticoids administered to a patient over the course of a year, adjusted for any changes in dosage, and measured up to the defined week of treatment as per protocol. |
| ANCA seronegativity and sustaining ANCA seronegativity until the analysis cutoff date | From randomization until the occurrence of an EFS event, up to approx. 4 years after randomization | ANCA seronegativity means that the patient tests negative for ANCA antibodies. |
| Change from baseline in estimated glomerular filtration rate (eGFR) at Week 39 | Up to Week 39 | Change from baseline in estimated glomerular filtration rate (eGFR) at Week 39. |
| Change from baseline in symptoms of GPA/ MPA using the AAV-PRO at Week 39 | Up to Week 39 | Change from baseline in symptoms of GPA/ MPA using the AAV-PRO at Week 39. |
| Change from baseline in Patient- Reported Outcome Measurement Information System (PROMIS)- Fatigue 7a at Week 91. | Up to Week 91 | Change from baseline in PROMIS- Fatigue 7a at Week 91. |
Countries
Brazil, Israel, Japan, Saudi Arabia, Singapore, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed