Clinical trial NCT06868290: Phase 2 Study Evaluating Rapcabtagene Autoleucel in Participants With Severe Active GPA or MPA
Official title: A Phase 2, Randomized, Open-label, Controlled Study to Evaluate the Efficacy and Safety of Rapcabtagene Autoleucel Versus Comparator in Participants With Severe Active Granulomatosis With Polyangiitis (GPA) or Microscopic Polyangiitis (MPA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: ANCA Associated Vasculitis (AAV)
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)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2025-03-10
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Event-free survival (EFS)
timeFrame: From randomization until the occurrence of an EFS event, up to approx. 4 years after randomization
Secondary outcomes:
measure: Percentage of patients achieving complete remission
timeFrame: Up to Week 13
measure: Adjusted annual cumulative GC dose between Randomization and analysis cutoff date
timeFrame: From randomization until the occurrence of an EFS event, up to approx. 4 years after randomization
measure: ANCA seronegativity and sustaining ANCA seronegativity until the analysis cutoff date
timeFrame: From randomization until the occurrence of an EFS event, up to approx. 4 years after randomization
measure: Change from baseline in estimated glomerular filtration rate (eGFR) at Week 39
timeFrame: Up to Week 39
measure: Change from baseline in symptoms of GPA/ MPA using the AAV-PRO at Week 39
timeFrame: Up to Week 39
measure: Change from baseline in Patient- Reported Outcome Measurement Information System (PROMIS)- Fatigue 7a at Week 91.
timeFrame: Up to Week 91
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Kobe
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Sendai city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Suita
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Chiba
country: Japan
facility: Novartis Investigative Site
city: Kyoto
country: Japan
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: