Clinical trial NCT06294236: Study Evaluating SC291 in Subjects With Severe r/r B-cell Mediated Autoimmune Diseases (GLEAM)
Official title: A Phase 1 Study Evaluating SC291, a Hypoimmune, Allogeneic CD19-directed CAR T Cell Therapy, in Subjects With Severe Relapsed or Refractory Autoimmune Diseases (GLEAM)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Lupus Erythematosus
Systemic Lupus Erythematosus
SLE (Systemic Lupus)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Granulomatous Polyangiitis
Microscopic Polyangiitis
Keywords: Autoimmune Disease
Systemic Lupus Erythematosus
Lupus Nephritis
Lupus
Extrarenal Lupus
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Granulomatous Polyangitis
Microscopic Polyangiitis
CAR T Cell Therapy
Allogeneic
Hypoimmune
CD19
Cyclophosphamide
Fludarabine
Cellular Therapy
SC291
ANCA Associated Vasculitis
SLE
ANCA
Vasculitis
Lead sponsor: Sana Biotechnology
Sponsor class: INDUSTRY
First posted: 2024-03-05
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: SC291-102 is a Phase 1 study to evaluate SC291 safety and tolerability, preliminary clinical response, cellular kinetics and exploratory assessments for subjects with severe autoimmune diseases.

Detailed description: Systemic lupus erythematosus (SLE) is an autoimmune disease with multisystemic organ involvement that is often fatal. SLE is subcategorized as extrarenal lupus (ERL) or lupus nephritis (LN). B cell depletion therapies have played an important role in the treatment of multiple B cell-driven autoimmune diseases.

Subjects included in this trial will be subjects with diagnoses of systemic lupus erythematosus (SLE) including lupus nephritis (LN) and extrarenal systemic lupus erythematosus (ERL), or anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (including Granulomatous Polyangitis and Microscopic Polyangiitis) who have refractory disease, have relapsed and have not shown appropriate clinical responses following prior systemic treatments.

This study is being conducted to evaluate the safety and efficacy of an investigational cell therapy, SC291, that can be given to patients with LN, ERL or AAV, in separate parallel cohorts, who have active disease.

A single dose of SC291 will be evaluated in patients who are pretreated with a standard regimen including cyclophosphamide (CY) and fludarabine (FLU).

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 and ≤75
2. For LN cohort:

   * Diagnosis of SLE based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)
   * Biopsy-proven LN class III or IV, according to 2018 Revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria
   * Refractory disease to ≥ 2 prior treatment regimens
3. For ERL cohort:

   * Diagnosis of SLE based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for adult SLE
   * Severe or relapsing disease not responding to at least 2 prior recent disease-modifying therapies
4. For AAV Cohort, diagnosed with Granulomatous Polyangiitis (GPA) or Microscopic Polyangiitis (MPA) based on the 2022 ACR/EULAR classification criteria

Exclusion Criteria:

1. Prior CD19-directed cell therapy including CAR T treatment or other genetically modified cell therapy (e.g., Natural Killer (NK) cell)
2. For LN and ERL Cohorts, central nervous system (CNS) lupus manifestations or history or presence of CNS disorder
3. For LN and ERL Cohorts, diagnosis of anti-phospholipid antibody syndrome
4. For AAV Cohort only, Diagnosis of Eosinophilic Granulomatosis with Polyangiitis (EGPA) as defined by the 2022 ACR/EULAR classification criteria for EGPA -

Primary outcomes:
measure: Evaluate safety and tolerability of SC291
timeFrame: 24 months
Secondary outcomes:
measure: Evaluate preliminary clinical response to SC291
timeFrame: 12 months
measure: Evaluate preliminary clinical response to SC291
timeFrame: 12 months
measure: Evaluate preliminary clinical response to SC291
timeFrame: 12 months
measure: Evaluate preliminary clinical response to SC291
timeFrame: 12 months
measure: Evaluate preliminary clinical response to SC291 (LN and ERL Cohorts)
timeFrame: 12 months
measure: Evaluate preliminary clinical response to SC291 (LN Cohort)
timeFrame: 12 months
measure: Evaluate preliminary clinical response to SC291 (ERL Cohort)
timeFrame: 12 months
measure: Evaluate preliminary clinical response to SC291 (AAV Cohort)
timeFrame: 12 months
measure: Evaluate preliminary clinical response to SC291 (AAV Cohort)
timeFrame: 12 months
measure: Evaluate cellular kinetics and persistence of SC291
timeFrame: 24 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
Study officials:
affiliation: Sana Biotechnology, Inc.
name: Kristen Lee
role: STUDY_DIRECTOR
References: