Idiopathic Inflammatory Myopathies
Conditions
Keywords
Chimeric Antigen Receptor T cells (CAR-T), rapcabtagene autoleucel, idiopathic inflammatory myopathies (IIM), dermatomyositis, Anti-Synthetase Syndrome, Immune-Mediated Necrotizing Myopathy, Interstitial Lung Disease
Brief summary
A Phase 2, randomized, open-label, controlled study to evaluate the efficacy and safety of rapcabtagene autoleucel versus comparator in participants with severe refractory idiopathic inflammatory myopathies (IIM)
Detailed description
This is a Phase 2, randomized, 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 a comparator option. Participants in the comparator arm whose signs and symptoms are not fully controlled may receive rapcabtagene autoleucel treatment once the participant is confirmed to be eligible After end of study (EOS), participants who received rapcabtagene autoleucel infusion will enter a long-term follow-up (LTFU) period after rapcabtagene autoleucel infusion. This LTFU will be described in a separate study protocol.
Interventions
BIOLOGICALRapcabtagene autoleucel
Single infusion of rapcabtagene autoleucel after lymphodepleting therapy with fludarabine (adjusted based on renal impairment) and cyclophosphamide daily for 3 days.
OTHERActive Comparator Option
Investigator choice of treatment as per protocol
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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 probable or definite myositis according to American College of Rheumatology/European League Against Rheumatism 2017 (ACR/EULAR 2017) criteria 2. Participants who had inadequate response to prior therapy 3. Diagnosed with active disease such as presence of at least 1 of the following criteria: abnormal enzyme levels assessed as secondary to IIM, or EMG demonstrating active disease, DM skin rash, muscle biopsy demonstrating active IIM, or MRI demonstrating active inflammation. 4. Participant must meet criteria for severe myositis such as presence of active muscle weakness. Key
Exclusion criteria
1. Any condition during Screening 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. BMI at Screening of ≤17 or ≥40 kg/m2 3. Severe muscle damage at Screening 4. Inadequate organ function 5. Hypersensitivity and/or contraindications to any product (including its ingredients) to be given to the participant as per the study protocol 6. Other inflammatory and non-inflammatory myopathies 7. Any medical conditions that are not related to IIM that would jeopardize the ability of the participant to tolerate CD19 CAR-T cell therapy Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving moderate- to-major improvement in Total Improvement Score (TIS) at Week 52 | Week 52 | The percentage of participants with a TIS of at least 40 at the 52nd week after the start of the study, corresponding to moderate-to-major improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted annual cumulative glucocorticoid dose up to Week 52 | Week 52 | The total amount of glucocorticoids administered over the course of a year measured up to the 52nd week of treatment. |
| Change from baseline in percent predicted Forced Vital Capacity (FVC%) at Week 52 | Baseline, Week 52 | The difference in the percentage of the predicted Forced Vital Capacity (FVC) from the start of the study to the 52nd week. |
| Proportion of participants achieving major improvement in TIS at Week 52 | Week 52 | The percentage of participants with a TIS of at least 60 at the 52nd week after the start of the study, corresponding to at least major improvement. |
| Change from baseline in Patient-Reported-Outcome Measurement Information System (PROMIS)-Fatigue 7a at Week 52 | Baseline, Week 52 | The difference in the fatigue levels reported by participants from the start of the study to the 52nd week. |
Countries
Australia, Brazil, France, Germany, Israel, Italy, Japan, Netherlands, Saudi Arabia, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed