SNP-ACTH Gel for Kidney Disease

Recruiting at 33 trial locations

Overseen By Nancy Klett, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cerium Pharmaceuticals, Inc.

Disqualifiers: Secondary nephropathy, Diabetes, Recent surgery, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

148 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol suggests that if you have relapsed after certain immunosuppressive therapies, you need to wait a specific period before joining: more than 3 months for glucocorticoids, calcineurin inhibitors, or mycophenolate mofetil; more than 6 months for chlorambucil or cyclophosphamide; and more than 12 months for rituximab. It doesn't specify about other medications, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug Rituximab for kidney disease?

Rituximab has shown effectiveness in reducing proteinuria (excess protein in urine) in patients with primary membranous nephropathy, a type of kidney disease, as demonstrated in well-powered randomized controlled trials. It is considered a valid alternative to other treatments like glucocorticoid-cyclophosphamide, although the optimal dosing and regimen are still being studied. ^{1 2 3 4 5}

What safety data exists for Rituximab and related treatments in humans?

Rituximab, used for various conditions, is generally considered safe but can have rare serious side effects like infections, low blood cell counts, and reactivation of hepatitis B. Some patients may experience low potassium levels or late-onset side effects like neutropenia (low white blood cell count) and hypogammaglobulinemia (low antibody levels), which increase infection risk. ^{3 6 7 8 9}

What makes the SNP-ACTH Gel treatment for kidney disease unique compared to other treatments?

The SNP-ACTH Gel treatment is unique because it combines Rituximab, a medication often used for autoimmune diseases and certain cancers, with a gel form of ACTH (adrenocorticotropic hormone), which may offer a novel approach to managing kidney disease by potentially reducing inflammation and modulating the immune system in a targeted manner. ^{10 11 12 13 14}

What is the purpose of this trial?

The goal of the Phase 3a part of this clinical trial is to determine the optimal dose that will be used in the Phase 3b part of this clinical trial. The goal of the Phase 3b part is to assess the efficacy of SNP-ACTH (1-39) Gel relative to rituximab in patients with primary membranous nephropathy (PMN) at month 24.

Eligibility Criteria

This trial is for patients with primary membranous nephropathy, a kidney disease. They should have a life expectancy over 24 months, confirmed diagnosis via biopsy or positive anti PLA2R antibody test if they have Nephrotic Syndrome, and be at high risk of worsening kidney function. Participants must not have had certain treatments recently and cannot have diabetes or sensitivity to porcine proteins.

Inclusion Criteria

You are at high risk for kidney function loss, according to the KDIGO 2021-Glomerular Diseases Guideline.

I had a good response to immune therapy but my condition worsened after stopping it for over a year.

I have been diagnosed with membranous nephropathy and tested positive for anti-PLA2R antibodies.

Exclusion Criteria

I have been diagnosed with secondary membranous nephropathy.

Your blood test showed a big decrease in a specific antibody within the past year.

Other exclusion criteria may apply

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 3a Treatment

Dose finding phase with SNP-ACTH Gel treatment at two different dose levels for 12 months

12 months

Regular assessments at months 2, 3, 4, 5, 6, 9, 12

Phase 3b Treatment

Comparison of SNP-ACTH Gel at optimal dose versus Rituximab over 12 months

12 months

Rituximab administered at month 1 and month 6

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Rituximab
• SNP-ACTH (1-39) Gel

Trial Overview The study is testing SNP-ACTH (1-39) Gel against Rituximab in two phases: Phase 3a to find the best dose and Phase 3b to compare their effectiveness after 24 months in treating primary membranous nephropathy.

Participant Groups

Group I: Phase 3b Cohort 1 Experimental Treatment 1 Intervention

Dose level to be confirmed once Phase 3a part is completed

Group II: Phase 3a Cohort 2 Experimental Treatment 1 Intervention

5 mg SNP-ACTH Gel sc injection 3 times per week

Group III: Phase 3a Cohort 1 Experimental Treatment 1 Intervention

3 mg SNP-ACTH Gel sc injection 3 times per week

Group IV: Phase 3b Cohort 2 Active Control 1 Intervention

Rituximab arm: Patients randomized to the rituximab arm will receive 1 g IV infusion on T0 (after baseline measures are collected) and day 15. A second course of rituximab 1g IV infusion will be administered 6 months after the first rituximab infusion and an additional 1 g IV infusion 14 days following the first 6-month infusion.

Rituximab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in European Union as MabThera for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in Canada as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Who Is Running the Clinical Trial?

Cerium Pharmaceuticals, Inc.

Lead Sponsor

Trials

1

Recruited

150+

Findings from Research

In a study of 34 patients with primary membranous nephropathy (PMN), low-dose rituximab (375 mg/m2) resulted in a complete response in only 14.7% and a partial response in 29.4% after 12 months, indicating limited efficacy.

The study suggests that higher doses and longer treatment durations may be necessary to improve response rates, as the current low-dose regimen achieved remission in less than half of the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose rituximab is poorly effective in patients with primary membranous nephropathy. Moroni, G., Depetri, F., Del Vecchio, L., et al.[2022]

In a survey of 380 nephrologists in Japan, only 21.8% reported using rituximab (RTX) for primary membranous nephropathy (pMN), compared to 47.6% for minimal change nephrotic syndrome (MCNS), indicating lower adoption of RTX for pMN despite its recommendation as a standard therapy.

The primary reason for withholding RTX in pMN cases was financial difficulties, with 79.3% of nephrologists citing challenges in securing funding for the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practice patterns of rituximab for primary membranous nephropathy 2021 in Japan: a web-based survey of board-certified nephrologists. Miyaoka, Y., Kurita, N., Sofue, T., et al.[2023]

Rituximab is primarily indicated for refractory immune thrombocytopenic purpura and is considered the best treatment for cold agglutinin disease, but its long-term benefit-to-risk ratio remains uncertain, especially in relation to splenectomy.

While rituximab shows promise in treating various autoimmune diseases, including Wegener granulomatosis and HCV-associated cryoglobulinemia, there are significant risks of adverse events, particularly infections and severe reactions in certain patient populations, highlighting the need for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab off label use for difficult-to-treat auto-immune diseases: reappraisal of benefits and risks. Sailler, L.[2022]

Titrating rituximab treatment based on circulating CD20 B cells in patients with idiopathic membranous nephropathy was as effective as the standard four-dose regimen, achieving similar rates of disease remission (25%) and persistent B cell depletion.

This B cell-driven approach significantly reduced treatment costs to approximately 3770.90 euros ($4902.20) compared to 13,977.60 euros ($18,170.80) for the standard protocol, while also minimizing the risk of severe adverse reactions associated with multiple doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Titrating rituximab to circulating B cells to optimize lymphocytolytic therapy in idiopathic membranous nephropathy. Cravedi, P., Ruggenenti, P., Sghirlanzoni, MC., et al.[2022]

Rituximab has been shown to be effective for achieving proteinuria remission in patients with primary membranous nephropathy, outperforming other treatments like renin-angiotensin system blockers and cyclosporine in well-powered randomized controlled trials.

Recent studies, including STARMEN and RI-CYCLO, confirmed the efficacy of glucocorticoid-cyclophosphamide for high-risk patients, while also establishing rituximab as a valid alternative, although the optimal treatment protocols for rituximab have yet to be fully explored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Clinical Trials Insights into the Treatment of Primary Membranous Nephropathy. Rojas-Rivera, J., Fervenza, FC., Ortiz, A.[2022]

In a study of 280 renal transplant patients, rituximab did not significantly reduce the incidence of biopsy-proven acute rejection (BPAR) compared to placebo, with rates of 16.7% and 21.2% respectively.

However, rituximab may be beneficial for immunologically high-risk patients, as those not receiving rituximab had a much higher rejection rate of 38.2%, and the treatment was found to be safe despite a higher occurrence of neutropenia in rituximab-treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab as induction therapy after renal transplantation: a randomized, double-blind, placebo-controlled study of efficacy and safety. van den Hoogen, MW., Kamburova, EG., Baas, MC., et al.[2023]

Rituximab is an effective treatment for nephrotic syndrome, but it can lead to rare cases of symptomatic hypokalemia, which is a low potassium level in the blood.

The report highlights two specific cases of hypokalemia following rituximab treatment, emphasizing the need for healthcare professionals to monitor potassium levels closely after administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypokalemia after rituximab administration in nephrotic syndrome: two case reports. Song, Y., Ding, L., An, X., et al.[2023]

In a study of 60 children with steroid-dependent nephrotic syndrome, rituximab (RTX) was found to be generally safe, with severe neutropenia occurring in 3 patients and hypogammaglobulinemia in 9 patients after treatment.

Despite these late-onset adverse events, severe infections were rare, with only 2 patients requiring hospitalization, indicating that RTX can be an effective treatment option with manageable risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late-onset adverse events after a single dose of rituximab in children with complicated steroid-dependent nephrotic syndrome. Fujinaga, S., Ozawa, K., Sakuraya, K., et al.[2018]

Rituximab (RTX) is effective for treating immune-mediated renal diseases, particularly ANCA-associated vasculitis, but carries risks of serious adverse events like progressive multifocal leucoencephalopathy and hepatitis B reactivation.

Patients may experience moderate to severe hypogammaglobulinemia and late-onset neutropenia, increasing their risk of infections, highlighting the need for careful monitoring and patient counseling, especially in women of childbearing age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab for immunologic renal disease: What the nephrologist needs to know. Kronbichler, A., Windpessl, M., Pieringer, H., et al.[2018]

The study developed a new nanoparticle formulation (TAC-BSA-NPs) for delivering tacrolimus, which showed a significant reduction in kidney distribution and functional nephrotoxicity compared to the standard drug formulation (Prograf®).

TAC-BSA-NPs demonstrated improved pharmacokinetics by enhancing drug blood levels and prolonging circulation time, while also achieving an 85% encapsulation efficiency, making it a safer delivery method for this hydrophobic drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bovine serum albumin nanoparticles for delivery of tacrolimus to reduce its kidney uptake and functional nephrotoxicity. Zhao, L., Zhou, Y., Gao, Y., et al.[2017]

Oligonucleotide-functionalized gold nanoparticles (AuNP) effectively deliver anticancer drugs doxorubicin (DOX) and actinomycin D (ActD), with the ability to control drug loading through tailored DNA sequences.

The study found that DOX binds more strongly to the nanoparticles compared to ActD, resulting in lower cytotoxicity concentrations for DOX-AuNP (IC50 of 5.6 μM) compared to ActD-AuNP (IC50 of 0.12 μM), indicating that the delivery system enhances the effectiveness of these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of the drug binding properties and cytotoxicity of DNA-capped nanoparticles designed as delivery vehicles for the anticancer agents doxorubicin and actinomycin D. Alexander, CM., Dabrowiak, JC., Maye, MM.[2013]

Cisplatin-loaded chitosan nanoparticles (CCNP) demonstrated effective cytotoxicity against MCF-7 human breast cancer cells with an IC50 of 4.085 µg/mL, indicating their potential as a successful drug delivery system.

In contrast, the cisplatin-loaded chitosan nanoparticles linked to rituximab (mAbCCNP) did not show any cytotoxic effect, suggesting that the targeting mechanism of rituximab was ineffective for this specific cancer cell line.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of cisplatin-loaded chitosan nanoparticles and rituximab-linked surfaces as target-specific injectable nano-formulations for combating cancer. Sultan, MH., Moni, SS., Madkhali, OA., et al.[2022]

The novel β-CD/PAA nanogel formulation for dexamethasone delivery shows faster and more effective inhibition of cell adhesion in inflammatory conditions compared to free dexamethasone, indicating enhanced therapeutic action.

This nanogel allows for lower doses of dexamethasone to achieve similar or better effects, which could reduce the adverse side effects commonly associated with glucocorticoid treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclodextrin-Based Nanohydrogels Containing Polyamidoamine Units: A New Dexamethasone Delivery System for Inflammatory Diseases. Argenziano, M., Dianzani, C., Ferrara, B., et al.[2020]

The newly developed targeting vector [(64)Cu-NOTA-8-Aoc-BBN(7-14)NH(2)] shows high selectivity and affinity for the gastrin-releasing peptide receptor (GRPr), with an IC(50) of 3.1 nM in prostate cancer cells, indicating its potential for targeted cancer therapy.

In vivo studies in mouse models demonstrated that this conjugate effectively localized to tumors with a significant uptake of 3.58% injected dose per gram at 1 hour post-injection, while showing minimal accumulation in the liver, suggesting a favorable safety profile and rapid renal clearance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[64Cu-NOTA-8-Aoc-BBN(7-14)NH2] targeting vector for positron-emission tomography imaging of gastrin-releasing peptide receptor-expressing tissues. Prasanphanich, AF., Nanda, PK., Rold, TL., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Low-dose rituximab is poorly effective in patients with primary membranous nephropathy. [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

Practice patterns of rituximab for primary membranous nephropathy 2021 in Japan: a web-based survey of board-certified nephrologists. [2023]

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

Rituximab off label use for difficult-to-treat auto-immune diseases: reappraisal of benefits and risks. [2022]

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

Titrating rituximab to circulating B cells to optimize lymphocytolytic therapy in idiopathic membranous nephropathy. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Recent Clinical Trials Insights into the Treatment of Primary Membranous Nephropathy. [2022]

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

Rituximab as induction therapy after renal transplantation: a randomized, double-blind, placebo-controlled study of efficacy and safety. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Hypokalemia after rituximab administration in nephrotic syndrome: two case reports. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Late-onset adverse events after a single dose of rituximab in children with complicated steroid-dependent nephrotic syndrome. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Rituximab for immunologic renal disease: What the nephrologist needs to know. [2018]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Bovine serum albumin nanoparticles for delivery of tacrolimus to reduce its kidney uptake and functional nephrotoxicity. [2017]

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

Investigation of the drug binding properties and cytotoxicity of DNA-capped nanoparticles designed as delivery vehicles for the anticancer agents doxorubicin and actinomycin D. [2013]

12. England pubmed.ncbi.nlm.nih.gov

Characterization of cisplatin-loaded chitosan nanoparticles and rituximab-linked surfaces as target-specific injectable nano-formulations for combating cancer. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Cyclodextrin-Based Nanohydrogels Containing Polyamidoamine Units: A New Dexamethasone Delivery System for Inflammatory Diseases. [2020]

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

[64Cu-NOTA-8-Aoc-BBN(7-14)NH2] targeting vector for positron-emission tomography imaging of gastrin-releasing peptide receptor-expressing tissues. [2022]