Study Evaluating SC291 in Subjects With Severe r/r B-cell Mediated Autoimmune Diseases (GLEAM) (GLEAM)

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Systemic Lupus Erythematosus; Microscopic Polyangiitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Lupus Erythematosus; SLE (Systemic Lupus); Granulomatous Polyangiitis
• Intervention / Treatment: Biological: SC291

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).

• Study Type: Interventional
• Enrollment (Estimated): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LN Cohort; SC291 with lymphodepleting therapy	Biological: SC291; SC291 is an allogeneic CAR T cell therapy; Other Names: Cyclophosphamide; Fludarabine
Experimental: ERL Cohort; SC291 with lymphodepleting therapy	Biological: SC291; SC291 is an allogeneic CAR T cell therapy; Other Names: Cyclophosphamide; Fludarabine
Experimental: AAV Cohort; SC291 with lymphodepleting therapy	Biological: SC291; SC291 is an allogeneic CAR T cell therapy; Other Names: Cyclophosphamide; Fludarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate safety and tolerability of SC291	Safety and Tolerability: Proportion of subjects experiencing adverse events and dose-limiting toxicities	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate preliminary clinical response to SC291	Change from baseline in renal function as measured by Estimated Glomerular Filtration Rate (eGFR) (calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation)	12 months
Evaluate preliminary clinical response to SC291	Change from baseline in proteinuria as measured by Urine Protein Creatinine Ratio (UPCR)	12 months
Evaluate preliminary clinical response to SC291	Duration of drug free remission	12 months
Evaluate preliminary clinical response to SC291	Time to relapse	12 months
Evaluate preliminary clinical response to SC291 (LN and ERL Cohorts)	Change from baseline of Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)	12 months
Evaluate preliminary clinical response to SC291 (LN Cohort)	Change in disease activity as measured by proportion of subjects achieving complete renal response or partial renal response	12 months
Evaluate preliminary clinical response to SC291 (ERL Cohort)	Change in disease activity as measured by proportion of subjects achieving modified Definitions Of Remission In Systemic Lupus Erythematosus (DORIS) remission	12 months
Evaluate preliminary clinical response to SC291 (AAV Cohort)	Change in disease activity as measured by proportion of subjects achieving remission (Birmingham Vasculitis Activity Score version 3 [BVAS v3] of 0)	12 months
Evaluate preliminary clinical response to SC291 (AAV Cohort)	Change in disease activity as measured by change from baseline in BVAS v3	12 months
Evaluate cellular kinetics and persistence of SC291	Levels of SC291 CAR+ T cells in the blood	24 months

Collaborators and Investigators

• Sponsor: Sana Biotechnology
• Investigators: Study Director: Kristen Lee, Sana Biotechnology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: February 12, 2024
• First Submitted That Met QC Criteria: February 27, 2024
• First Posted (Actual): March 5, 2024

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Lupus; SLE; Cyclophosphamide; Systemic Lupus Erythematosus; Allogeneic; CD19; Vasculitis; Fludarabine; Autoimmune Disease; Lupus Nephritis; Cellular Therapy; ANCA; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; ANCA Associated Vasculitis; CAR T Cell Therapy; Hypoimmune; Extrarenal Lupus; Granulomatous Polyangitis; SC291
• Additional Relevant MeSH Terms: Urogenital Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Skin Diseases; Skin Diseases, Vascular; Lung Diseases, Interstitial; Glomerulonephritis; Nephritis; Cerebral Small Vessel Diseases; Systemic Vasculitis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Autoimmune Diseases; Granulomatosis with Polyangiitis; Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: SC291-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No