ADI-001 for Lupus Nephritis

Recruiting at 2 trial locations

Overseen By Adicet Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Adicet Bio, Inc

Disqualifiers: Severe liver disease, Gene therapy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ADI-001, a type of CAR-T cell therapy, for individuals with lupus nephritis, where lupus causes kidney inflammation. The trial aims to determine the right dose of ADI-001 and assess its safety and effectiveness. Participants will receive ADI-001 along with cyclophosphamide and fludarabine. Those diagnosed with lupus affecting the kidneys or other organs, who have not responded well to standard treatments, might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should have an inadequate response to current treatments, which might imply that some medications could be continued. Please consult with the trial team for specific guidance.

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

Research shows that ADI-001, an experimental treatment, is undergoing safety testing for autoimmune diseases. ADI-001 targets B-cells, a component of the immune system, using a specialized T-cell therapy. In earlier studies, ADI-001 significantly reduced B-cell numbers, similar to other treatments in academic research.

The current research is in an early stage, focusing on determining the right dose and assessing patient tolerance. This phase prioritizes safety, with close monitoring of side effects and patient responses. While detailed safety data isn't yet available, the emphasis on dose determination highlights the importance of understanding the body's reaction to ADI-001 in these trials.

Cyclophosphamide and Fludarabine often prepare the body for treatments like ADI-001. These well-known medications have a long history of use in various treatments, providing insight into their safety. However, monitoring their specific interactions with ADI-001 remains crucial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lupus nephritis?

Unlike the standard treatments for lupus nephritis, which often include corticosteroids and immunosuppressive drugs like mycophenolate mofetil, ADI-001 offers a novel approach by utilizing a unique mechanism of action. ADI-001 is a type of cell therapy, specifically an allogeneic gamma delta T-cell therapy, which targets the disease more directly at the cellular level. This innovative treatment harnesses the power of engineered immune cells to potentially offer a more targeted and effective approach, reducing the risk of broad immune suppression seen with traditional therapies. Researchers are excited about ADI-001 because it could provide a more precise treatment option with potentially fewer side effects and better outcomes for patients with lupus nephritis.

What evidence suggests that ADI-001 could be an effective treatment for lupus nephritis?

Research shows that ADI-001 could help treat autoimmune diseases. In earlier studies, all patients quickly and significantly improved in important disease activity scores, suggesting lasting effects. ADI-001 targets B-cells, which are part of the immune system and play a role in autoimmune diseases, and has effectively reduced these cells. This treatment uses a special cell therapy called CAR T cell therapy to attack harmful immune cells. These findings provide encouraging evidence that ADI-001 might be effective for conditions like lupus nephritis. Participants in this trial will receive ADI-001 in different dosing regimens to determine the optimal dose and further investigate its safety and efficacy. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for people with lupus nephritis, a type of kidney inflammation due to systemic lupus erythematosus. Participants must have an active disease confirmed by a biopsy within the last 6 months and significant protein in their urine. They should be able to perform daily activities with some limitations (ECOG ≤ 2).

Inclusion Criteria

Proteinuria (or urine protein creatinine ratio (UPCR)) > 1g / 24 hours

I have been diagnosed with systemic lupus erythematosus according to the 2019 criteria.

I am able to care for myself and perform daily activities.

Exclusion Criteria

I have not had gene or cell therapy treatments before.

LN pure class V, per 2018 ISN/RPS criteria (Bajema 2018)

My liver disease is severe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo lymphodepletion to prepare for the infusion of ADI-001

1 week

Treatment

Participants receive ADI-001 infusion with dose escalation to determine MTD/MAD

4 weeks

Weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• ADI-001
• Cyclophosphamide
• Fludarabine

Trial Overview The study tests ADI-001, alongside Cyclophosphamide and Fludarabine, for safety and effectiveness in treating lupus nephritis. It's an early-stage trial that includes screening, lymphodepletion (reducing certain white blood cells), treatment administration, and follow-up.

How Is the Trial Designed?

Group I: ADI-001 Dose Extension Experimental Treatment 3 Interventions

After dose level has been declared safe, additional patients can be enrolled at the declared safe dose to further investigate the safety profile of ADI-001.

Group II: ADI-001 Dose Expansion Experimental Treatment 3 Interventions

Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).

Group III: ADI-001 Dose Escalation Experimental Treatment 3 Interventions

ADI-001 is administered via infusion with ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-001.

Who Is Running the Clinical Trial?

Adicet Bio, Inc

Lead Sponsor

Trials

3

Recruited

310+

Adicet Therapeutics

Lead Sponsor

Trials

4

Recruited

370+

Published Research Related to This Trial

In a study involving 5 patients with lupus nephritis, both subcutaneous and intravenous administration of fludarabine showed similar pharmacokinetics, indicating that the method of delivery does not significantly affect the drug's absorption and effectiveness.

Subcutaneous administration of fludarabine demonstrated approximately 105% bioavailability compared to intravenous delivery, and no injection site reactions were reported, suggesting it could be a more convenient and equally effective alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine pharmacokinetics after subcutaneous and intravenous administration in patients with lupus nephritis. Kuo, GM., Boumpas, DT., Illei, GG., et al.[2019]

A 6-month outpatient treatment with high-dose oral cyclophosphamide showed improvements in disease activity for most patients with systemic lupus erythematosus (SLE), particularly those with nephritis, as indicated by better SLAM scores and reduced proteinuria.

While the treatment was generally feasible, some patients experienced mild nausea and infections, and three patients did not complete the therapy due to various reasons, suggesting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient monthly oral bolus cyclophosphamide therapy in systemic lupus erythematosus. Dawisha, SM., Yarboro, CH., Vaughan, EM., et al.[2021]

High-dose corticosteroids are the standard initial treatment for severe inflammation in lupus nephritis, but long-term management often requires additional therapies to address underlying immune system issues.

New treatment options for lupus nephritis include novel immunosuppressive agents and combination therapies, which may improve efficacy and reduce toxicity compared to traditional treatments like cyclophosphamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in the treatment of proliferative lupus nephritis. Balow, JE., Austin, HA.[2019]

In a study of 46 patients with systemic lupus erythematosus nephritis treated with oral cyclophosphamide (POCY), 70% achieved durable remission of proteinuria, indicating its effectiveness as a treatment option.

POCY was well tolerated, with adverse effects occurring in less than 10% of patients, suggesting it is a safe alternative to intravenous cyclophosphamide (IVCY) for managing lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral cyclophosphamide for lupus glomerulonephritis: an underused therapeutic option. McKinley, A., Park, E., Spetie, D., et al.[2022]

Tacrolimus (TAC) demonstrated significant efficacy in treating lupus nephritis (LN), with 75% of patients achieving complete remission after 12 months, compared to only 40% in the cyclophosphamide (CYC) group.

TAC was associated with fewer severe adverse effects, as the CYC group had cases of end-stage renal disease and serious pneumonia, highlighting TAC's safety profile in patients with severe renal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus versus cyclophosphamide as treatment for diffuse proliferative or membranous lupus nephritis: a non-randomized prospective cohort study. Wang, S., Li, X., Qu, L., et al.[2022]

A short course of low-dose fludarabine combined with cyclophosphamide can lead to significant improvements in patients with active proliferative lupus nephritis, with 10 out of 11 evaluated patients showing marked improvement and 7 achieving complete remission.

However, the treatment was associated with severe bone marrow toxicity, including profound lymphocytopenia and serious adverse events, which limits its safety and widespread use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of combination treatment with fludarabine and low-dose pulse cyclophosphamide in patients with lupus nephritis. Illei, GG., Yarboro, CH., Kuroiwa, T., et al.[2013]

This study involves a prospective randomized trial with 12 patients suffering from systemic lupus erythematosus (SLE) and nephritis, focusing on the effects of monthly intravenous cyclophosphamide administration.

Preliminary data suggests that cyclophosphamide may be a potential treatment option for managing SLE-related nephritis, although further results are needed to assess its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cyclophosphamide pulse therapy of systemic lupus erythematosus with renal involvement]. Hein, R., Neumann, KH., Koch, KM., et al.[2014]

In a study of 17 patients with refractory lupus nephritis, rituximab treatment led to complete or partial renal remission in 53% of cases after 12 months, indicating its potential efficacy as an alternative treatment.

Rituximab also significantly improved proteinuria levels and allowed for a reduction in steroid dosages, suggesting it may help manage the side effects associated with standard treatments like corticosteroids and cyclophosphamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the effectiveness and safety of rituximab in patients with refractory lupus nephritis: a chart review. Contis, A., Vanquaethem, H., Truchetet, ME., et al.[2022]

In a study of 77 lupus nephritis patients, those with the GSTA1*A heterozygous mutation had a higher risk of not achieving remission from cyclophosphamide therapy (44% vs. 20%).

Pharmacokinetic analysis showed that patients with the GSTA1*A variant had lower levels of the active metabolite 4-hydroxycyclophosphamide, which was linked to poorer treatment outcomes, indicating that genetic factors can influence the effectiveness of cyclophosphamide in lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The GSTA1 polymorphism and cyclophosphamide therapy outcomes in lupus nephritis patients. Wang, HN., Zhu, XY., Zhu, Y., et al.[2015]

In a study comparing two treatment methods for diffuse proliferative lupus nephritis, sequential oral cyclophosphamide (CYC) followed by azathioprine (AZA) showed a trend towards better efficacy, with 90% of patients achieving complete or partial remission compared to 73% in the intravenous (IV) CYC group.

While the oral treatment had a higher rate of herpes zoster infections and menstrual disturbances, these side effects were not statistically significant, indicating that although oral CYC and AZA may be more effective, they could also lead to increased toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of diffuse proliferative lupus glomerulonephritis: a comparison of two cyclophosphamide-containing regimens. Mok, CC., Ho, CT., Siu, YP., et al.[2022]

Cyclophosphamide (CYC) is still the first-choice treatment for severe proliferative lupus nephritis, despite the availability of newer treatment options.

There is ongoing debate regarding the optimal route, dosage, and duration of CYC therapy, highlighting the need for further research to refine treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lupus nephritis: current issues. Mavragani, CP., Moutsopoulos, HM.[2019]

Citations

1. investor.adicetbio.com investor.adicetbio.com/news-releases/news-release-details/adicet-bio-announces-positive-preliminary-data-adi-001-phase-1

Adicet Bio Announces Positive Preliminary Data from ADI ... 100% of patients saw rapid and sustained reductions in SLEDAI-2K and PGA scores, highlighting ADI-001's potential durable effect on a broad ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06375993

A Phase 1 Study of ADI-001 in Autoimmune Disease ADI-202300103 is a phase 1 multicenter, open label, dose finding and dose expansion, safety/efficacy study in patients with autoimmune disease.

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/adicet-adi-001-trial/

Adicet Bio doses first SSc subject in second cohort of trial ... In the Phase I GLEAN trial, ADI-001 demonstrated the ability to target B-cells, showing strong exposure and complete CD19+ B-cell depletion in ...

4. tandem.confex.com tandem.confex.com/tandem/2023/meetingapp.cgi/Paper/21031

A Phase 1 Study of ADI-001: Anti-CD20 CAR-Engineered ... ADI-001 is a first-in-class allogeneic gamma delta (γδ) CAR T cell therapy targeting the B-cell antigen CD20. ADI-001 has both adaptive and innate cytotoxic ...

5. rarediseaseadvisor.com rarediseaseadvisor.com/news/first-patient-dosed-trial-adi-001-autoimmune-ssc/

First Patient Dosed in Phase 1 Trial of ADI-001 for SSc The first patient was dosed in a phase 1 trial of ADI-001 for autoimmune diseases, including systemic sclerosis (SSc), SLE, AAV, and others.

6. rheumatologyadvisor.com rheumatologyadvisor.com/news/gamma-delta-car-t-cell-therapy-fast-tracked-for-sle-with-extrarenal-involvement/

Gamma Delta CAR T-Cell Therapy Fast Tracked for SLE ... The FDA has granted Fast Track designation to ADI-001 for the treatment of refractory systemic lupus erythematosus with extrarenal involvement ...

7. sec.gov sec.gov/Archives/edgar/data/1720580/000095017024001490/acet-ex99_1.htm

EX-99.1 Clinical data for ADI-001 have demonstrated B-cell depletion that mirrors the B cell depletion by autologous alpha-beta CAR T in academic clinical studies in ...