CB-010 for Lupus

(GALLOP Trial)

Overseen By Caribou Biosciences

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Caribou Biosciences, Inc.

Must be taking: Glucocorticoids, Immunosuppressives

Must not be taking: Live vaccines

Disqualifiers: CNS lupus, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 1 study to evaluate the safety and efficacy of a single infusion of CB-010 in patients with refractory Systemic Lupus Erythematosus (SLE) with cohorts for lupus nephritis (LN) and extrarenal lupus (ERL).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should be refractory (not responding) to certain treatments, which might imply that you should continue your current medications if they are not effective.

What data supports the effectiveness of the treatment CB-010 for Lupus?

Research shows that a similar treatment using CD19-targeted CAR T cells led to significant improvement in lupus symptoms in both mice and humans, with patients experiencing remission and reduced disease activity. This suggests that the CB-010 treatment, which also targets CD19, could be effective for lupus. ^{1 2 3 4 5}

Is CB-010 (CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy) safe for humans?

Research on anti-CD19 CAR T cell therapy, which is similar to CB-010, shows it is generally well tolerated in patients with systemic lupus erythematosus (SLE), with only mild side effects like cytokine-release syndrome (a mild immune reaction). This suggests it may be safe for humans, but more studies are needed to confirm this. ^{1 2 3 5 6}

How is the CB-010 treatment for lupus different from other treatments?

CB-010 is a unique treatment for lupus because it uses CRISPR-edited allogeneic anti-CD19 CAR-T cells, which are engineered immune cells designed to target and eliminate B cells that contribute to lupus. This approach is different from traditional treatments as it aims to reset the immune system and has shown promise in achieving drug-free remission in patients who do not respond to standard therapies. ^{1 2 3 4 7}

Eligibility Criteria

This trial is for patients with severe lupus, specifically those with Class III or IV lupus nephritis and a high protein-to-creatinine ratio in their urine. Participants must have tried at least two immunosuppressive therapies without success and be up to date on vaccinations. Women of childbearing age must use effective contraception.

Inclusion Criteria

My condition did not improve after using steroids and two other immune-suppressing drugs.

I have been diagnosed with lupus for at least 6 months.

I have severe lupus affecting my kidneys.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single infusion of CB-010

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy

Trial Overview The GALLOP study is testing the safety and effectiveness of CB-010, a CRISPR-edited anti-CD19 CAR-T cell therapy. This Phase 1 trial involves one infusion for people with refractory Systemic Lupus Erythematosus (SLE), including both kidney-involved (lupus nephritis) and non-kidney (extrarenal) cases.

Participant Groups

Group I: Cohort 2 Extrarenal Lupus (ERL) Experimental Treatment 1 Intervention

Group II: Cohort 1 Lupus Nephritis (LN) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Caribou Biosciences, Inc.

Lead Sponsor

Trials

5

Recruited

360+

Findings from Research

Using CAR T cells to continuously deplete B cells leads to remission of lupus symptoms in mice that are genetically predisposed to the disease, suggesting a potential therapeutic strategy for lupus.

This study highlights the effectiveness of targeted cell therapy in managing autoimmune diseases, demonstrating that manipulating the immune system can result in significant health improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slamming the brakes on lupus with CAR T cells. Clark, RA.[2019]

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]

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]

Complete and sustained depletion of CD19+ B cells using CD19-targeted CAR T cells was shown to be a highly effective therapy in lupus models, significantly reversing disease symptoms and extending lifespan in mouse models of lupus.

This approach demonstrated long-lasting effects, with CAR T cells remaining active for up to one year, suggesting that sustained B cell depletion could be a promising strategy for treating lupus in humans, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. Kansal, R., Richardson, N., Neeli, I., et al.[2021]

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]

References

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

Slamming the brakes on lupus with CAR T cells. [2019]

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

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

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

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

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

Reversal of autoimmune disease in lupus-prone New Zealand black/New Zealand white mice by nonmyeloablative transplantation of purified allogeneic hematopoietic stem cells. [2021]

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

Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. [2021]

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

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

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

Abrogated AID Function Prolongs Survival and Diminishes Renal Pathology in the BXSB Mouse Model of Systemic Lupus Erythematosus. [2021]