SC291 for Autoimmune Diseases

(GLEAM Trial)

Recruiting at 4 trial locations

Overseen By Sana Biotechnology, Inc

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sana Biotechnology

Disqualifiers: CNS lupus, CNS disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SC291 to evaluate its safety and effectiveness for people with severe autoimmune diseases. It targets individuals with serious conditions like lupus nephritis (a type of lupus affecting the kidneys) that haven't improved with at least two treatments, or those with certain types of vasculitis (inflammation of blood vessels) such as GPA or MPA. Participants will receive SC291 along with therapy that reduces immune cells. This trial may suit those struggling with these conditions despite trying other treatments. As a Phase 1 trial, participants will be among the first to receive SC291, aiding researchers in understanding how this new treatment works in people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that SC291 is likely to be safe for humans?

Research shows that SC291 has promising safety results. In earlier studies, patients generally tolerated SC291 well. One study found that the immune system did not detect it, and it helped a patient with chronic lymphocytic leukemia improve partially. This suggests the treatment might also be safe for people with severe autoimmune diseases. However, since SC291 remains in early testing, more information is needed to fully understand its safety. Always consult a doctor before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for autoimmune diseases, which often include immunosuppressants and biologics like methotrexate or infliximab, SC291 offers a fresh approach by incorporating lymphodepleting therapy. This unique strategy aims to reset the immune system, potentially reducing the autoimmune response more effectively. Researchers are excited about SC291 because it targets the underlying cause of autoimmune disorders rather than just managing symptoms, offering hope for long-term relief. Additionally, by specifically altering immune cell populations, SC291 might provide a more tailored treatment with fewer side effects compared to broad-spectrum immunosuppressants.

What evidence suggests that SC291 might be an effective treatment for autoimmune diseases?

Research has shown that SC291, a type of cell therapy, targets and reduces certain immune cells known as CD19+ cells. One study demonstrated a 95% reduction in these cells on the first day and a 99% reduction after 28 days. This suggests that SC291 could effectively lower the harmful immune cells involved in autoimmune diseases. Participants in this trial will receive SC291 with lymphodepleting therapy, designed to minimize rejection by the body's immune system, making it a promising option for treating severe autoimmune conditions like lupus and similar diseases. ^{2 4 5 6 7}

Who Is on the Research Team?

Kristen Lee

Principal Investigator

Sana Biotechnology, Inc.

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with severe autoimmune diseases like Wegener's Granulomatosis, Lupus, and Vasculitis. Participants must have a specific diagnosis based on EULAR/ACR criteria and not responded to at least two prior treatments. People with CNS lupus manifestations, anti-phospholipid antibody syndrome, or previous CD19-directed cell therapy are excluded.

Inclusion Criteria

I have been diagnosed with GPA or MPA according to the 2022 criteria.

I have lupus with kidney involvement and my previous treatments haven't worked.

I have severe lupus not improved by at least two recent treatments.

Exclusion Criteria

I have lupus affecting my brain or a history of brain disorders, and I do not have anti-phospholipid antibody syndrome.

I have been diagnosed with EGPA according to the 2022 criteria.

I have previously received CAR T-cell therapy or similar treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive a standard regimen including cyclophosphamide (CY) and fludarabine (FLU) for lymphodepletion

1-2 weeks

Treatment

A single dose of SC291 is administered to participants

1 day

Follow-up

Participants are monitored for safety, tolerability, and clinical response to SC291

24 months

What Are the Treatments Tested in This Trial?

Interventions

• SC291

Trial Overview The study is testing SC291's safety and effectiveness in treating severe refractory B-cell mediated autoimmune diseases. It will look at how the body responds to the drug, its side effects, and any signs of improvement in disease symptoms.

How Is the Trial Designed?

Group I: LN Cohort Experimental Treatment 1 Intervention

SC291 with lymphodepleting therapy

Group II: ERL Cohort Experimental Treatment 1 Intervention

SC291 with lymphodepleting therapy

Group III: AAV Cohort Experimental Treatment 1 Intervention

SC291 with lymphodepleting therapy

Who Is Running the Clinical Trial?

Sana Biotechnology

Lead Sponsor

Trials

5

Recruited

12,100+

Published Research Related to This Trial

Hematopoietic stem cell transplantation (HSCT) has been effectively used since 1995 to treat severe, treatment-resistant autoimmune diseases, with strong evidence supporting its use in conditions like multiple sclerosis, systemic sclerosis, and Crohn's disease based on large studies and randomized controlled trials.

The mechanism of action for HSCT involves not only its anti-inflammatory and immunosuppressive effects but also the potential to 'reset' the immune system, enhancing T-regulatory cell activity and promoting long-term immune tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haematopoietic stem cell transplantation in autoimmune diseases: From basic science to clinical practice. Kelsey, PJ., Oliveira, MC., Badoglio, M., et al.[2021]

In a study of 23 patients with primary Sjögren's syndrome and refractory immune thrombocytopenia, tacrolimus (TAC) demonstrated significant efficacy, with 60.9% achieving a complete response and 34.8% achieving a partial response after 24 weeks of treatment.

TAC treatment was well tolerated and associated with a reduction in Th1 cytokine expression, as evidenced by decreased levels of IgG, CD3+ T cell counts, and inflammatory markers, suggesting a beneficial immunomodulatory effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus therapy in primary Sjögren's syndrome with refractory immune thrombocytopenia: a retrospective study. Xu, R., Yan, Q., Gong, Y., et al.[2022]

In a study of 53 juvenile systemic lupus erythematosus (JSLE) patients, urinary levels of soluble alpha chain of the interleukin-2 receptor (sCD25) were significantly higher compared to healthy controls, indicating its potential as a marker for disease activity.

Patients with active lupus nephritis (LN) showed even higher sCD25 levels, and these concentrations correlated positively with various disease activity measures, suggesting that urinary sCD25 could be a useful tool for monitoring renal involvement in JSLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary soluble alpha chain of the interleukin-2 receptor as a biomarker of active lupus nephritis in Egyptian children with juvenile systemic lupus erythematosus. Hassan, W., Behiry, E., Mahgoub, M.[2022]

CD19 acts as a crucial adapter protein that enhances B lymphocyte signaling and is linked to autoantibody production, particularly in patients with systemic sclerosis, where its overexpression correlates with increased autoantibodies.

CD22 serves as a significant regulator of CD19's function, indicating that the interplay between these two molecules is essential for controlling B cell activation and may play a role in the development of autoimmune conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 and CD22 regulate a B lymphocyte signal transduction pathway that contributes to autoimmunity. Tedder, TF., Sato, S., Poe, JC., et al.[2019]

SM03, an anti-CD22 monoclonal antibody, has shown promising safety and efficacy in treating rheumatoid arthritis and systemic lupus erythematosus, with its unique mechanism of action being a key factor in its therapeutic success.

The mechanism involves disrupting CD22's configuration on B cells, enhancing immune tolerance to host tissues while preserving the immune response to pathogens, which may explain the observed improvements in disease symptoms and safety in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SM03, an Anti-CD22 Antibody, Converts Cis-to-Trans Ligand Binding of CD22 against α2,6-Linked Sialic Acid Glycans and Immunomodulates Systemic Autoimmune Diseases. Wong, KL., Li, Z., Ma, F., et al.[2022]

A specific genetic variant (SNP rs763361/Gly307Ser) in the CD226 gene is strongly associated with an increased risk of type 1 diabetes (T1D) and shows potential links to multiple sclerosis (MS) and autoimmune thyroid disease (AITD), based on a study involving 2088 T1D cases and 3289 controls.

The Ser(307) allele of this SNP may be a causal variant for these autoimmune diseases, highlighting a common genetic pathway that could inform future research and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD226 Gly307Ser association with multiple autoimmune diseases. Hafler, JP., Maier, LM., Cooper, JD., et al.[2022]

B cells are crucial in autoimmune diseases, not just through producing autoantibodies but also by various other functions influenced by their environment.

The interaction between CD19 and CD22, which regulates B cell signaling, is linked to autoimmune disease in mice, suggesting that targeting this 'CD19/CD22 loop' could be a promising therapeutic strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B cell signaling and autoimmune diseases: CD19/CD22 loop as a B cell signaling device to regulate the balance of autoimmunity. Fujimoto, M., Sato, S.[2012]

In a study involving 100 patients with refractory low-prevalence autoimmune diseases, targeted therapies prescribed off-label were found to be effective in 56% of cases, leading to a significant reduction in corticosteroid use for those who responded.

The safety profile was acceptable, with a low incidence of serious infections (14.8 per 100 patient-years) and only one case of cancer, indicating that these therapies can be tolerated by patients with a long history of immunosuppressive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerance and efficacy of targeted therapies prescribed for off-label indications in refractory systemic autoimmune diseases: data of the first 100 patients enrolled in the TATA registry (TArgeted Therapy in Autoimmune Diseases). Gottenberg, JE., Chaudier, A., Allenbach, Y., et al.[2022]

Tocilizumab, an anti-IL-6 receptor monoclonal antibody, has been shown to effectively improve symptoms and functional status in patients with rheumatoid arthritis (RA) based on data from randomized controlled trials.

In addition to symptom relief, tocilizumab may also inhibit the progression of RA as seen in radiographic assessments, indicating its potential as a long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-6 inhibition and clinical efficacy in rheumatoid arthritis treatment--data from randomized clinical trials. Kavanaugh, A.[2022]

A study involving 265 multiplex families identified a specific genetic variant (rs2476601) in the PTPN22 gene that increases the risk for multiple autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, and Hashimoto thyroiditis.

The research suggests that while there may be shared genetic factors among some autoimmune disorders, multiple sclerosis appears to have a distinct pathogenesis, indicating the complexity of autoimmune disease mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes. Criswell, LA., Pfeiffer, KA., Lum, RF., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06294236

Study Evaluating SC291 in Subjects With Severe r/r B-cell ... 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, ...

2. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/6852/500451/Phase-1-Study-of-SC291-a-Hypoimmune-Allogeneic

Phase 1 Study of SC291, a Hypoimmune, Allogeneic CD19 ... Interestingly, with the LD regimen used, we observed a 95% and 99% reduction of CD19+ cells on Days 0 and 28, respectively, while T cells ...

3. ir.sana.com ir.sana.com/news-releases/news-release-details/sana-biotechnology-announces-fast-track-designation-sc291

Release Details - Investor Relations | Sana Biotechnology, Inc SC291, a hypoimmune (HIP)-modified CD19-directed allogeneic CAR T therapy, is being evaluated in Sana's GLEAM trial in patients with B-cell ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1934590925002668

Hypoimmune CD19 CAR T cells evade allorejection in ... This study focuses on the immune response of patients against SC291 and does not report safety or primary efficacy outcome measures of ARDENT or ...

5. cgtlive.com cgtlive.com/view/sc291-car-t-cell-therapy-fast-tracked-relapsed-refractory-sle

SC291 CAR T-Cell Therapy Fast Tracked for Relapsed ... Sana Biotechnology's SC291 chimeric antigen receptor T-cell therapy is being developed to treat relapsed/refractory systemic lupus erythematosus.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06294236

NCT06294236 | Study Evaluating SC291 in Subjects With ... 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.

7. ir.sana.com ir.sana.com/news-releases/news-release-details/sana-biotechnology-publishes-early-clinical-data-showing-sc291

Release Details - Investor Relations | Sana Biotechnology, Inc SC291 appeared safe and well tolerated, evaded immune detection, and induced a partial response in a patient with chronic lymphocytic leukemia ( ...