Clinical trial NCT06665256: Phase 2 Study of Rapcabtagene Autoleucel in Myositis
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 Refractory Idiopathic Inflammatory Myopathies (IIM)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Idiopathic Inflammatory Myopathies
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-10-30
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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, two-year, 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 a comparator option.

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 ≤65 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
4. Participant must meet criteria for severe myositis

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 ≤18.5 or ≥35 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/exclusion criteria may apply.

Primary outcomes:
measure: Proportion of participants achieving at least moderate improvement in Total Improvement Score (TIS) at Week 52
timeFrame: Week 52
Secondary outcomes:
measure: Adjusted annual cumulative glucocorticoid dose up to Week 52
timeFrame: Week 52
measure: Change from baseline in percent predicted Forced Vital Capacity (FVC%) at Week 52
timeFrame: Baseline, Week 52
measure: Proportion of participants achieving major improvement in TIS at Week 52
timeFrame: Week 52
measure: Change from baseline in Patient-Reported-Outcome Measurement Information System (PROMIS)-Fatigue 7a at Week 52
timeFrame: Baseline, Week 52
measure: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Week 104
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Iowa City
country: United States
facility: University Of Iowa
state: Iowa
city: Brest
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Rennes
country: France
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
state: Sachsen
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Kanazawa
country: Japan
facility: Novartis Investigative Site
state: Ishikawa
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: Kyoto
country: Japan
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: