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

Phase 1

Recruiting

• Conditions: Lupus Erythematosus; Systemic Lupus Erythematosus; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; SLE (Systemic Lupus); Granulomatous Polyangiitis; Microscopic Polyangiitis
• Interventions: Biological: SC291

• Registration Number: NCT06294236
• Lead Sponsor: Sana Biotechnology

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).

Study Timeline

• Study First Submitted: 2024-02-12
• Study First Submitted QC: 2024-02-27
• Study First Posted: 2024-03-05
• Study Start: 2024-04-29
• Status Verified: 2024-05
• Last Update Submitted: 2024-11-05
• Last Update Posted: 2024-11-07
• Primary Completion: 2027-12
• Study Completion: 2028-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

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

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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 -

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ERL Cohort	SC291	SC291 with lymphodepleting therapy
LN Cohort	SC291	SC291 with lymphodepleting therapy
AAV Cohort	SC291	SC291 with lymphodepleting therapy

Primary Outcome Measures

Name	Time	Method
Evaluate safety and tolerability of SC291	24 months	Safety and Tolerability: Proportion of subjects experiencing adverse events and dose-limiting toxicities

Secondary Outcome Measures

Name	Time	Method
Evaluate cellular kinetics and persistence of SC291	24 months	Levels of SC291 CAR+ T cells in the blood
Evaluate preliminary clinical response to SC291 (LN and ERL Cohorts)	12 months	Change from baseline of Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
Evaluate preliminary clinical response to SC291 (LN Cohort)	12 months	Change in disease activity as measured by proportion of subjects achieving complete renal response or partial renal response
Evaluate preliminary clinical response to SC291 (ERL Cohort)	12 months	Change in disease activity as measured by proportion of subjects achieving modified Definitions Of Remission In Systemic Lupus Erythematosus (DORIS) remission
Evaluate preliminary clinical response to SC291	12 months	Time to relapse
Evaluate preliminary clinical response to SC291 (AAV Cohort)	12 months	Change in disease activity as measured by change from baseline in BVAS v3

Trial Locations

Locations (5)

Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Swedish Medical Center; 🇺🇸 Seattle, Washington, United States