SYNCAR-001 + STK-009 for Lupus

Recruiting at 4 trial locations

Overseen By Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Synthekine

Disqualifiers: CNS manifestations, Gene therapy, Dialysis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 28 days

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 1 study of SYNCAR-001 + STK-009 in patients with severe, refractory systemic autoimmune rheumatic disease.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment SYNCAR-001 + STK-009 for Lupus?

Research shows that a similar treatment, anti-CD19 CAR T cell therapy, has been effective in patients with systemic lupus erythematosus (SLE), leading to remission and improvement of symptoms. This therapy works by targeting and depleting B cells, which are involved in the disease, and has been well tolerated by patients. ^{1 2 3 4 5}

Is the SYNCAR-001 + STK-009 treatment safe for humans?

The treatment, involving anti-CD19 CAR T cells, has been tested in patients with systemic lupus erythematosus (SLE) and was generally well tolerated, with only mild side effects like cytokine-release syndrome (a mild immune reaction). This suggests that the treatment is safe for human use, at least in the context of SLE. ^{1 2 3 4 5}

How is the SYNCAR-001 + STK-009 treatment for lupus different from other treatments?

The SYNCAR-001 + STK-009 treatment is unique because it involves using a patient's own modified immune cells (CAR T cells) to target and deplete B cells, which are involved in lupus. This approach has shown promise in achieving remission in patients who do not respond to standard therapies, offering a novel mechanism compared to traditional immunosuppressive drugs. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults over 18 with severe, treatment-resistant systemic lupus erythematosus (SLE). Participants must have a clinical diagnosis of SLE and test positive for certain autoantibodies. It's not suitable for those with mild SLE or conditions that could interfere with the study.

Inclusion Criteria

Clinical diagnosis of SLE according to the 2019 European League Rheumatism EULAR/ACR classification criteria

I tested positive for at least one specific antibody related to my condition.

I have severe lupus not affecting my kidneys or active kidney lupus.

Exclusion Criteria

I have or had lupus affecting my brain or spinal cord.

My kidney disease is worsening quickly.

I am on dialysis or my latest kidney biopsy showed chronic damage.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

A single fixed dose of autologous SYNCAR-001 CAR-T is administered intravenously, followed by multiple subcutaneous doses of STK-009

Up to 28 days

Multiple visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and disease activity

96 weeks

Treatment Details

Interventions

• STK-009
• SYNCAR-001

Trial Overview The trial is testing SYNCAR-001 combined with STK-009 as a potential treatment for severe SLE. This phase 1 study aims to evaluate the safety and how well patients tolerate this combination therapy.

Participant Groups

Group I: SYNCAR-001 + STK-009 Experimental Treatment 2 Interventions

Dose escalation: A single fixed dose of autologous SYNCAR-001 CAR-T intravenously (IV) will be administered in combination with ascending doses of STK-009 subcutaneously (SC) in non-lymphodepleted patients. Dose expansion: A single fixed dose of autologous SYNCAR-001 CAR-T IV will be administered in combination with STK-009 SC at the RP2D in non-lymphodepleted patients.

STK-009 is already approved in United States for the following indications:

Approved in United States as STK-009 for:

• None approved; under investigation for CD19+ hematologic malignancies and systemic lupus erythematosus (SLE)

Who Is Running the Clinical Trial?

Synthekine

Lead Sponsor

Trials

3

Recruited

290+

Findings from Research

In a study involving five patients with severe systemic lupus erythematosus (SLE), treatment with CAR T cells targeting CD19 led to complete remission of the disease in all participants after 3 months, demonstrating high efficacy.

The CAR T cell therapy was well tolerated, with only mild side effects, and patients maintained drug-free remission for an average of 8 months, even after B cells reappeared, indicating a durable response to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Mackensen, A., Müller, F., Mougiakakos, D., et al.[2023]

In a study of six patients with refractory systemic lupus erythematosus (SLE), anti-CD19 CAR T cell therapy was found to be well tolerated and led to a significant reduction in inflammatory cytokines IL-6 and TNFα three months after treatment.

The therapy also resulted in a marked decrease in SLE-associated antibodies in five out of six patients, suggesting a potential mechanism for its efficacy in managing SLE symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. Nunez, D., Patel, D., Volkov, J., et al.[2023]

In a study involving six patients with systemic lupus erythematosus (SLE), researchers successfully produced functional anti-CD19 CAR T cells from their T cells, demonstrating that leukapheresis can yield sufficient T-cell numbers for clinical-scale production despite the challenges posed by autoimmune conditions.

The generated CAR T cells exhibited high expansion rates, viability, and specific cytotoxicity against CD19+ cell lines in vitro, indicating that CAR T-cell therapy can be effectively developed for patients with autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Generation of CD19 Chimeric Antigen Receptor T Cells from Patients with Advanced Systemic Lupus Erythematosus. Kretschmann, S., Völkl, S., Reimann, H., et al.[2023]

Anti-CD19 CAR-T cell therapy demonstrated effective B-cell depletion in a mouse model of systemic lupus erythematosus (SLE), showing both preventive and therapeutic benefits against the disease.

CAR-T cells using the 4-1BB costimulatory motif were found to be more effective than those using the CD28 motif, suggesting a promising strategy for optimizing treatment in SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus. Jin, X., Xu, Q., Pu, C., et al.[2022]

In a small study of five treatment-resistant patients with systemic lupus erythematosus (SLE), CD19 CAR T cell therapy led to significant clinical improvements and remission in all participants after 3 months, demonstrating its potential efficacy.

The treatment was well tolerated, with only mild cytokine release syndrome reported, suggesting a favorable safety profile for this innovative therapy in seriously ill SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus. Boulougoura, A., Gendelman, H., Surmachevska, N., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Successful Generation of CD19 Chimeric Antigen Receptor T Cells from Patients with Advanced Systemic Lupus Erythematosus. [2023]

4. China pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus. [2023]