C-CAR168 CAR T Cell Therapy for Autoimmune Diseases

Overseen By Nurat Quadri, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AbelZeta Inc.

Must not be taking: Live vaccines, Rituximab

Disqualifiers: Hepatitis, HIV, Organ transplant, others

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

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called C-CAR168, a type of CAR T cell therapy designed to help people with autoimmune diseases that haven't responded to standard treatments. The trial aims to determine the treatment's safety and effectiveness at different doses. Participants will receive an infusion of the treatment and be monitored for up to 24 months. Individuals with lupus, an ongoing autoimmune disease, who have active symptoms and haven't found success with other treatments, might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, the research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

You will need to temporarily stop taking immunosuppressive medications at least 7 days before a procedure called leukapheresis. Additionally, you may need to taper off steroids before this procedure.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that C-CAR168, a type of CAR-T cell therapy, has promising safety results from earlier studies. Initial tests demonstrated that the treatment was well-tolerated and maintained a good safety record. These studies examined its effects on patients with autoimmune diseases unresponsive to standard treatments.

C-CAR168 targets two proteins, CD20 and BCMA, which play roles in immune responses. This dual-targeting method has undergone testing for both effectiveness and safety in lab settings. While more research is needed, human testing suggests that the initial safety data is encouraging.

This study is in the early stages (Phase 1/2), focusing on the treatment's safety and patient tolerance. Participants will receive varying doses to find the best balance between safety and effectiveness. As with any trial, researchers will closely monitor participants for any possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for autoimmune diseases?

Researchers are excited about C-CAR168 CAR T Cell Therapy for autoimmune diseases because it offers a novel approach compared to standard treatments like corticosteroids or immunosuppressants. Unlike these conventional therapies, which broadly suppress the immune system, C-CAR168 harnesses the power of genetically engineered T cells to specifically target and modulate immune responses. This precision has the potential to reduce unwanted side effects and improve effectiveness. Additionally, the therapy's ability to directly reprogram T cells represents a groundbreaking shift in treatment strategy, potentially leading to longer-lasting remission for patients.

What evidence suggests that C-CAR168 could be an effective treatment for autoimmune diseases?

Research has shown that C-CAR168 could help treat autoimmune diseases that resist standard treatments. This trial will explore different dose levels of C-CAR168, a CAR-T cell therapy targeting specific proteins on immune cells (CD20 and BCMA), to assess its effectiveness in reducing symptoms and improving conditions like lupus nephritis, a kidney problem caused by lupus. Early clinical results demonstrated lower protein levels in urine and improved kidney function. Although more research is needed, initial findings are promising for those with difficult-to-treat autoimmune conditions. ^{2 3 5 6 7}

Who Is on the Research Team?

Scott Antonia

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for patients with autoimmune diseases like Purpura Nephritis and Lupus, who haven't responded to standard treatments. They must be able to taper off steroids before leukapheresis, stop immunosuppressants before the procedure, and possibly receive steroids again if needed.

Inclusion Criteria

No active infection within 2 weeks before leukapheresis

Voluntary signed informed consent required

Life Expectancy greater than 6 months

Exclusion Criteria

Positive for Hepatitis B surface antigen (HBsAg)/core antibody (HBcAb)/e antibody (HBeAb)/e antigen (HBeAg), Hepatitis C Virus (HCV) antibodies, Human Immunodeficiency Virus (HIV) antibodies, or syphilis antigen or antibody

Received Prednisone treatment of ≥ 100 mg/d or equivalent corticosteroid therapy for ≥14 days within the previous 8 weeks; plasma exchange, plasma separation, hemodialysis, or IVIG within 14 days prior to leukapheresis; other investigational clinical study drug within 28 days prior to leukapheresis; CAR-T cell products or other genetically modified T cell therapies; Rituximab/ocrelizumab/obinutuzumab within 6 months prior to screening

Pregnant or breastfeeding women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Leukapheresis and Bridging Therapy

Participants taper steroid use, undergo leukapheresis for C-CAR168 manufacturing, and may receive bridging therapy to maintain disease stability.

3-4 weeks

2 visits (in-person)

Lymphodepletion and Treatment

Participants undergo lymphodepletion therapy followed by a single intravenous infusion of C-CAR168.

1 week

1 visit (in-person)

Dose Limiting Toxicity Evaluation

Participants are monitored for dose-limiting toxicities during the first 28 days post-infusion.

4 weeks

Weekly visits (in-person)

Follow-up

Participants attend regular safety and efficacy assessments for up to 24 months post-infusion.

24 months

Regular visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• C-CAR168

Trial Overview

The study tests C-CAR168 CAR T Cell Therapy's safety and tolerability in a Phase 1/2 trial. It involves dose finding and expansion phases for those with refractory autoimmune diseases, including lymphodepletion therapy followed by a single infusion of C-CAR168.

How Is the Trial Designed?

Group I: Arm 5: Dose Expansion Cohort Experimental Treatment 1 Intervention

Dose: To be selected based on MTD/RD identified in escalation phase. 12-24 additional subjects will be treated at the selected dose level. No staggered dosing required.

Group II: Arm 4: Dose Level 3 (DL3) Experimental Treatment 1 Intervention

Dose: 2.0 × 10⁶ CAR+ cells/kg Optional dose level pending SRC review and approval.

Group III: Arm 3: Dose Level 2 (DL2) Experimental Treatment 1 Intervention

Dose: 1.5 × 10⁶ CAR+ cells/kg Second dose level in escalation phase. Subject enrollment staggered by 28 days.

Group IV: Arm 2: Dose Level 1 (DL1) Experimental Treatment 1 Intervention

Dose: 0.75 × 10⁶ CAR+ cells/kg Starting dose for escalation phase. First 3 subjects must be staggered by 28 days.

Group V: Arm 1: Dose Level -1 (DL-1) Experimental Treatment 1 Intervention

0.5 × 10⁶ CAR+ cells/kg Optional dose level, administered only upon Safety Review Committee (SRC) recommendation.

Who Is Running the Clinical Trial?

AbelZeta Inc.

Lead Sponsor

AbelZeta, Inc.

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

CAR T-cell therapy is a powerful immunotherapy that not only shows promise in treating various cancers but can also be adapted to target autoimmune diseases and infections like HIV.

The therapy utilizes engineered T cells that can recognize a wider range of targets compared to natural T cells, enhancing its potential effectiveness in diverse medical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of CAR-T cell technology in autoimmune diseases and human immunodeficiency virus infection treatment. Adabi, N., Pordel, S., Rezaee, MA., et al.[2023]

CAR T cell therapy, particularly with the approval of tisagenlecleucel, has shown remarkable efficacy in treating pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia, with six therapies approved as of April 2023 for B-cell malignancies and multiple myeloma.

However, the therapy is associated with significant adverse events like cytokine release syndrome, which are more severe with higher pretreatment tumor burdens; thus, initiating therapy early or using a debulking strategy may help mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From bench to bedside: the history and progress of CAR T cell therapy. Mitra, A., Barua, A., Huang, L., et al.[2023]

Adoptive transfer of engineered T cells, specifically CAR T cells, shows promise as a potential curative therapy for autoimmune disorders, with early clinical results indicating effectiveness in conditions like systemic lupus erythematosus and myasthenia gravis.

Innovative approaches, such as chimeric autoantibody receptor T cells, are being developed to target specific B cell clones responsible for autoantibody production, while regulatory CAR T cells aim to modulate rather than eliminate autoreactive immune cells, highlighting a nuanced strategy in treating autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells for treating autoimmune diseases. Blache, U., Tretbar, S., Koehl, U., et al.[2023]

In a study involving 1,926 subjects from 17 clinical trials, patients with acute lymphocytic leukemia (ALL) were found to have a higher risk of severe cytokine release syndrome (sCRS) and severe neurological toxicities (sNTX) compared to those with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM).

The use of CAR T cells produced with gammaretrovirus vectors containing CD28 sequences was linked to increased rates of sNTX, while administering cytokine-directed therapies and corticosteroids at lower toxicity grades was associated with reduced rates of sCRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. Foster, M., Negash, Y., Eberhardt, L., et al.[2022]

A systematic analysis of CAR T-cell therapy adverse events revealed 5,112 reports of hematotoxicity, highlighting significant under-reporting of severe conditions like hemophagocytic lymphohistiocytosis (HLH) and disseminated intravascular coagulation (DIC), which have high mortality rates of 69.9% and 59.6%, respectively.

The study identified 23 hematologic adverse events that were significantly over-reported compared to the general database, emphasizing the need for increased awareness and monitoring of these rare but potentially fatal toxicities in CAR T therapy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy. Song, Z., Tu, D., Tang, G., et al.[2023]

Chimeric antigen receptor (CAR)-based therapies, originally developed for cancer treatment, are showing promise in treating autoimmune diseases by using CAR-T cells to target and deplete harmful immune cells, leading to favorable outcomes.

CAR-T regulatory T cells (Tregs) have potential in restoring immune tolerance in autoimmune diseases, and advancements in gene editing and synthetic biology are enhancing the effectiveness and safety of these CAR-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARs: a new approach for the treatment of autoimmune diseases. Sun, Y., Yuan, Y., Zhang, B., et al.[2023]

CAR T-cell therapy can lead to significant toxicities, particularly cytokine release syndrome (CRS) and neurologic toxicities, which require careful monitoring and management.

Recent guidelines and evidence-based practices are evolving to help healthcare professionals, especially nurses, effectively assess and manage these toxicities to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associated Toxicities: Assessment and Management Related to CAR T-Cell Therapy. Anderson, K., Latchford, T.[2020]

Citations

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NCT06249438 | A Study of C-CAR168 in the Treatment ...

This is an investigator-initiated, multicenter, open-label study of C-CAR168, an autologous bi-specific CAR-T therapy targeting CD20 and BCMA, ...

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AbelZeta Presents New Data on C-CAR168 for the ...

Early clinical results for C-CAR168 mark a significant step forward in the treatment of patients suffering from LN and SPMS with severe ...

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jrheum.org/content/52/Suppl_1/25

CLINICAL IMPACT OF C-CAR168, A NOVEL ANTI-CD20 ...

Initial results show promising efficacy and safety of C-CAR168 treatment in refractory LN, with reduced proteinuria, preserved renal function and improvement ...

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C-CAR168 as a Novel Anti-CD20/BCMA Bispecific ...

Evidence from B cell malignancies suggests that CD20 CAR-T might result in better survival in diffuse large B-cell lymphoma (DLBCL) than CD19 CAR-T and could ...

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AbelZeta Presents Preclinical Data from Study of C- ...

C-CAR168 is a novel autologous bi-specific CAR-T therapy targeting both CD20 and B-cell maturation antigen (BCMA) for the treatment of resistant and refractory ...

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AbelZeta Presents New Data on C-CAR168 for the ...

This is an investigator-initiated, multicenter, open-label study of C-CAR168 for the treatment of adult patients with autoimmune diseases and neurological ...