IMPT-514 for Lupus

No longer recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ImmPACT Bio

Must be taking: Autoimmune medications

Disqualifiers: Other autoimmune, CNS lupus, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called IMPT-514 for individuals with stubborn lupus and lupus nephritis, a severe kidney condition linked to lupus. The treatment involves a one-time infusion of specially modified immune cells to target and attack the disease. Researchers will monitor participants for about a year after the treatment and follow them for up to 15 years to assess long-term effects. This trial suits individuals with active lupus or lupus nephritis who have been stable on their current lupus medications for at least four weeks. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop taking your current medications. However, you need to be on a stable dose of your autoimmune disease medications for at least 4 weeks before screening.

Is there any evidence suggesting that IMPT-514 is likely to be safe for humans?

Research has shown that IMPT-514, a therapy using modified cells to target specific proteins, holds promise for treating conditions like lupus without causing serious side effects. In earlier studies, participants reported no nerve damage, and cytokine release syndrome (CRS), a common side effect, was mild and manageable.

While specific safety data for lupus nephritis remains unspecified, the treatment is in early testing stages, with safety under close observation. Early trials typically focus on safety, ensuring that any major side effects are quickly identified and addressed.

Overall, for those considering joining this trial, it is reassuring that IMPT-514 has been well-tolerated in early research, with only mild side effects observed so far. ^{1 2 3 4 5}

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

Researchers are excited about IMPT-514 for lupus because it offers a fresh approach compared to existing treatments like corticosteroids, immunosuppressants, and biologics such as belimumab. Unlike these standard therapies, which generally suppress the immune system broadly, IMPT-514 is believed to target specific pathways involved in lupus, potentially leading to more precise effects with fewer side effects. This targeted mechanism could mean better management of lupus symptoms and possibly improved outcomes for patients. Additionally, IMPT-514 might be effective for both systemic lupus erythematosus and lupus nephritis, providing a versatile option for individuals suffering from these conditions.

What evidence suggests that IMPT-514 might be an effective treatment for lupus?

Research has shown that IMPT-514 could be a promising treatment for lupus, particularly for systemic lupus erythematosus (SLE) and lupus nephritis. This trial will evaluate IMPT-514 in different phases for these conditions. The treatment employs a special therapy with CAR-T cells, which are immune cells modified to attack two proteins, CD19 and CD20, on B cells involved in lupus. Laboratory studies have demonstrated that IMPT-514 can be produced even in patients with strong immune suppression, such as those with lupus. Although limited data from human trials exist, its mechanism suggests it could effectively reduce disease activity by targeting these B cells. Early signs are hopeful, but further research is needed to confirm its efficacy. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with active, refractory systemic lupus erythematosus (SLE) or lupus nephritis. Participants must weigh over 45 kg, have controlled blood pressure, and meet specific SLE diagnostic criteria. It's not suitable for those with other significant illnesses, additional autoimmune conditions, aggressive kidney inflammation, active CNS lupus, or a history of organ transplantation.

Inclusion Criteria

Other protocol-defined criteria apply.

My blood pressure is under control.

I have been diagnosed with SLE according to 2019 EULAR/ACR or 2012 SLICC criteria.

Exclusion Criteria

I have had a bone marrow, stem cell, or organ transplant.

Any clinically significant underlying illness, other than SLE and LN, which would pose a safety risk or concern, as determined by the Investigator

I have active lupus affecting my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Therapy

Participants receive a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide

1-2 weeks

Treatment

Participants receive a single infusion of CAR-transduced autologous T cells administered intravenously

1 day

Active Post-Treatment

Participants remain in the active post-treatment period for monitoring

1 year

Long-term Follow-up

Participants are monitored for safety and effectiveness for 15 years from treatment

15 years

What Are the Treatments Tested in This Trial?

Interventions

• IMPT-514

Trial Overview The study tests IMPT-514 in patients with tough-to-treat SLE and lupus nephritis. IMPT-514 is a dual-target CAR therapy given via one-time infusion after pre-treatment to reduce immune cells. Patients are observed for safety and effectiveness for about a year post-treatment and followed up long-term for 15 years.

How Is the Trial Designed?

Group I: Phase 2 SLE without Lupus Nephritis Experimental Treatment 1 Intervention

Administration of IMPT-514

Group II: Phase 2 Lupus Nephritis Experimental Treatment 1 Intervention

Administration of IMPT-514

Group III: Phase 1 Lupus Nephritis Experimental Treatment 1 Intervention

Administration of IMPT-514

IMPT-514 is already approved in United States for the following indications:

Approved in United States as IMPT-514 for:

• Active refractory lupus nephritis
• Systemic lupus erythematosus

Who Is Running the Clinical Trial?

ImmPACT Bio

Lead Sponsor

Trials

2

Recruited

150+

Lyell Immunopharma, Inc.

Lead Sponsor

Trials

5

Recruited

610+

Published Research Related to This Trial

In a case series of six Japanese children with severe lupus nephritis, prompt initiation of methylprednisolone pulse therapy followed by oral prednisolone and cyclophosphamide led to significant reductions in urine protein excretion and disease activity after 8 months.

At the latest follow-up (mean 53 months), all patients showed clinical and serological improvement, with complete remission in two patients and no cases of renal impairment, suggesting the treatment protocol may be beneficial for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylprednisolone pulse therapy in Japanese children with severe lupus nephritis. Tanaka, H., Tateyama, T., Waga, S.[2019]

MAIT cells play a significant role in worsening lupus symptoms in a mouse model by increasing autoantibody production and tissue inflammation, as shown in FcγRIIb-/-Yaa mice.

Targeting MAIT cell activation with an inhibitory MR1 ligand reduced autoantibody levels and kidney damage in these mice, suggesting that MAIT cells could be potential therapeutic targets for treating autoimmune diseases like lupus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Critical Role for Mucosal-Associated Invariant T Cells as Regulators and Therapeutic Targets in Systemic Lupus Erythematosus. Murayama, G., Chiba, A., Suzuki, H., et al.[2020]

In a 10-year follow-up of 90 patients from the Euro-Lupus Nephritis Trial, low-dose intravenous cyclophosphamide followed by azathioprine showed similar long-term outcomes in terms of survival and kidney function compared to high-dose treatment.

An early reduction in proteinuria after initial immunosuppressive therapy was confirmed as a strong predictor of a good long-term outcome, highlighting the importance of monitoring this marker in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Houssiau, FA., Vasconcelos, C., D'Cruz, D., et al.[2022]

Recent clinical trials have significantly influenced the updated guidelines for managing lupus nephritis, indicating a shift towards more effective treatment strategies.

The review also addresses important challenges such as the cost of therapies, the issue of resistant disease, and potential adverse effects associated with specific treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Lupus Nephritis: New Treatments and Updated Guidelines. Avasare, R., Drexler, Y., Caster, DJ., et al.[2023]

Belimumab significantly reduced the time to achieve 30% and 40% decreases in estimated glomerular filtration rate (eGFR) in patients with lupus nephritis, indicating its efficacy in improving kidney function.

The treatment was particularly effective in patients with proliferative lupus nephritis, but showed no added benefit for those with nephrotic range proteinuria or those receiving cyclophosphamide/azathioprine, suggesting that patient selection is crucial for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BLISS-LN trial revisited: function matters. Gleeson, S., Lightstone, L.[2022]

BMS-986126 is a highly selective inhibitor of IRAK4 that effectively suppresses MyD88-dependent immune responses, showing promise in reducing cytokine production from various TLR agonists in mouse models.

In lupus models, BMS-986126 not only inhibited pathogenic responses but also demonstrated potential for steroid-sparing effects when used in combination with prednisolone, indicating its therapeutic benefit for lupus treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective IRAK4 Inhibition Attenuates Disease in Murine Lupus Models and Demonstrates Steroid Sparing Activity. Dudhgaonkar, S., Ranade, S., Nagar, J., et al.[2018]

In a study of 52 patients with systemic lupus erythematosus (SLE), researchers identified a significantly expanded population of PD-1hiCXCR5-CD4+ T peripheral helper (Tph) cells that are linked to B cell activation and disease activity.

The presence of Tph cells correlated with clinical disease severity and B cell numbers in the kidneys of SLE patients, indicating their potential as a target for therapies aimed at modulating harmful B cell responses in this autoimmune disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. Bocharnikov, AV., Keegan, J., Wacleche, VS., et al.[2022]

In a study of 38 Portuguese patients with Systemic Lupus Erythematosus (SLE), belimumab demonstrated significant effectiveness, with SLE Responder Index (SRI) response rates increasing from 51.9% at 6 months to 91.7% at 24 months, indicating a reduction in disease activity.

Belimumab was associated with a good safety profile, with only five patients experiencing adverse events, primarily infections, and the treatment led to a significant decrease in disease activity markers and daily steroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab in the treatment of Portuguese Systemic Lupus Erythematosus patients: a real-life multicenter study. Fernandes, BM., Barreira, S., Fonseca, JE., et al.[2021]

Belimumab is an effective and generally well-tolerated treatment for systemic lupus erythematosus (SLE), showing a low incidence of organ damage when used long-term alongside standard therapies, particularly in patients at high risk for organ dysfunction.

This systematic review of randomized clinical trials from 2005 to 2021 indicates that belimumab can significantly improve SLE symptoms and reduce reliance on steroids, with greater efficacy observed in children and across different racial groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Belimumab in Systemic Lupus Erythematosis: A Systematic Review. Joy, A., Muralidharan, A., Alfaraj, M., et al.[2022]

Belimumab is the first biologic approved for systemic lupus erythematosus (SLE) and has been shown to effectively reduce disease activity and the risk of severe flares, allowing patients to reduce their use of glucocorticoids.

It has also been approved for treating active lupus nephritis, with studies showing that patients receiving belimumab alongside standard therapy had better renal responses and lower risks of renal-related events compared to those receiving standard therapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

10 Years of belimumab experience: What have we learnt? Levy, RA., Gonzalez-Rivera, T., Khamashta, M., et al.[2022]

In a retrospective study of 16 patients with systemic lupus erythematosus (SLE) receiving belimumab (BEL), three patients with severe lupus nephritis showed significant reductions in proteinuria, indicating BEL's potential efficacy in this non-approved indication.

One patient with neuropsychiatric systemic lupus erythematosus (NPSLE) experienced clinical improvement after BEL treatment, suggesting that BEL may also benefit patients with this severe manifestation, although careful patient selection is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy of Routinely Administered Belimumab on Proteinuria and Neuropsychiatric Lupus. Plüß, M., Tampe, B., Niebusch, N., et al.[2020]

Chronic treatment with anti-L3T4 monoclonal antibodies in lupus-prone mice effectively depleted L3T4+ cells from the spleen and lymph nodes, preventing symptoms like splenomegaly and lymphadenopathy, while also preventing thymic atrophy.

Despite reducing L3T4+ cells, the treatment did not impair the overall immune response of splenic lymphocytes and even enhanced natural killer cell activity, while significantly decreasing kidney damage and other autoimmune symptoms associated with murine lupus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of murine lupus with monoclonal antibody to L3T4. I. Effects on the distribution and function of lymphocyte subsets and on the histopathology of autoimmune disease. Wofsy, D., Chiang, NY., Greenspan, JS., et al.[2019]

Belimumab is an effective and safe treatment for Systemic Lupus Erythematosus (SLE), as supported by multiple phase III clinical trials showing higher SLE Responder Index (SRI) in treated patients.

However, there is a potential risk of acute pancreatitis associated with belimumab, with 0.21% of users reporting this side effect, particularly in females aged 40-49, indicating the need for further research on this adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Pancreatitis After the Use of Belimumab in a Patient With Systemic Lupus Erythematosus: Case Report and Review of Literature. Bazigh, I., Asfour, M., Muddassir, S., et al.[2022]

In a post-hoc analysis of data from two Phase IIb trials involving 736 patients with moderate to severe Systemic Lupus Erythematosus (SLE), those who achieved a Systemic Lupus Erythematosus Responder Index (SRI(4)) response at Week 52 showed significantly greater improvements in various clinical outcomes compared to nonresponders.

SRI(4) responders also reported better patient-reported outcomes, indicating that achieving this response is linked to overall clinical benefit in managing SLE, particularly in reducing disease activity and improving quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Lupus Erythematosus (SLE) Responder Index response is associated with global benefit for patients with SLE. Furie, R., Wang, L., Illei, G., et al.[2019]

The study found that the rs2227513 SNP in the IL-22 gene is associated with an increased risk of systemic lupus erythematosus (SLE) in a Chinese population, with an adjusted odds ratio of 2.24, indicating a significant genetic risk factor.

Patients with the AG genotype of rs2227513 not only had a higher risk of developing SLE but also faced an increased risk of renal disorders related to SLE, suggesting that this genetic variant may lower IL-22 expression and contribute to disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of interleukin 22 gene polymorphisms and serum IL-22 level with risk of systemic lupus erythematosus in a Chinese population. Wang, R., Zeng, YL., Qin, HM., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06153095

NCT06153095 | A Study of IMPT-514 in Active Refractory ... This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of IMPT-514, a bispecific chimeric antigen receptor (CAR) targeting ...

2. trials.arthritis.org trials.arthritis.org/trials/NCT06153095

A Study of IMPT-514 in Active Refractory Systemic Lupus ... This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of IMPT-514, a bispecific chimeric antigen receptor (CAR) targeting ...

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/immpact-bio-lupus-nephritis-trial/

ImmPACT Bio receives grant for lupus nephritis treatment trial IMPT-514 was effectively produced from heavily immunosuppressed patients with LN and SLE in preclinical studies. The therapy also demonstrated ...

4. synapse.patsnap.com synapse.patsnap.com/article/8m-cirm-grant-supports-impt-514-car-t-cell-therapy-for-lupus

$8M CIRM Grant Supports IMPT-514 CAR T-Cell Therapy ... The initial efficacy and safety data from the Phase 1b/2 dose escalation trial of IMPT-514 are anticipated in the latter half of 2024, offering ...

5. withpower.com withpower.com/trial/phase-2-nephritis-11-2023-4d182

IMPT-514 for Lupus · Info for Participants The available research does not provide specific data on the effectiveness of IMPT-514 for Lupus. Instead, it discusses other treatments like belimumab and ...

6. cgtlive.com cgtlive.com/view/immpact-bio-systemic-lupus-erythematosus-car-t-cleared-us-trial

ImmPACT Bio's Systemic Lupus Erythematosus CAR-T ... “The robust data package for IMPT-514 includes compelling phase 1 safety data ... IMPT-514 for the treatment of refractory systemic lupus ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06153095?cond=lupus&intr=CAR-T%20&limit=100&page=1&rank=13

A Study of IMPT-514 in Active Refractory Lupus Nephritis ... This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of IMPT-514, a bispecific chimeric antigen receptor (CAR) targeting ...