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

Systemic Lupus Erythematosus Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06294236
• Other study ID #: SC291-102
• Status: Recruiting
• Phase: Phase 1
• Start date: April 29, 2024
• Est. completion date: March 2028

Study information

• Verified date: May 2024
• Source: Sana Biotechnology
• Contact: Sana Biotechnology, Inc
• Phone: (206) 707-9904
• Email: Gleam[@]sana.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: March 2028
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 -

Related Conditions & MeSH terms

• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
• Autoimmune Diseases
• Granulomatosis with Polyangiitis
• Lupus Erythematosus
• Lupus Erythematosus, Systemic
• Microscopic Polyangiitis
• SLE (Systemic Lupus)
• Systemic Lupus Erythematosus
• Systemic Vasculitis
• Vasculitis

Intervention

Biological:
• SC291
SC291 is an allogeneic CAR T cell therapy

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Swedish Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Sana Biotechnology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate safety and tolerability of SC291	Safety and Tolerability: Proportion of subjects experiencing adverse events and dose-limiting toxicities	24 months
Secondary	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
Secondary	Evaluate preliminary clinical response to SC291	Change from baseline in proteinuria as measured by Urine Protein Creatinine Ratio (UPCR)	12 months
Secondary	Evaluate preliminary clinical response to SC291	Duration of drug free remission	12 months
Secondary	Evaluate preliminary clinical response to SC291	Time to relapse	12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Evaluate preliminary clinical response to SC291 (AAV Cohort)	Change in disease activity as measured by change from baseline in BVAS v3	12 months
Secondary	Evaluate cellular kinetics and persistence of SC291	Levels of SC291 CAR+ T cells in the blood	24 months