Povetacicept for Autoimmune Kidney Diseases

(RUBY-3 Trial)

Not currently recruiting at 43 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Alpine Immune Sciences, Inc.

Must be taking: ACEis/ARBs

Must not be taking: B cell depleting

Disqualifiers: Other renal disease, eGFR <30, others

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

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores povetacicept, a new treatment option, to determine its safety and effectiveness for individuals with certain autoimmune kidney diseases. It targets those with immunoglobulin A nephropathy (IgAN), primary membranous nephropathy (pMN), lupus nephritis (LN), or ANCA-associated vasculitis (AAV). Participants will receive the treatment every four weeks for 6-12 months, with possible extensions. Ideal candidates have a confirmed diagnosis of these conditions and have not responded to standard kidney disease treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, for some conditions, you should not be on background immunosuppression therapies, except for certain cases like lupus nephritis where stable immunosuppression is required. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that povetacicept is likely to be safe for humans?

Research shows that povetacicept may help treat certain autoimmune diseases. Early studies indicate it is generally safe and well-tolerated in people. These initial studies, which focus on safety, suggest that further testing in autoimmune and inflammatory diseases is worthwhile.

While specific side effects aren't listed, studies so far suggest that any reported issues are manageable. This trial includes both early and mid-phase studies, indicating the treatment has passed some initial safety tests but is still being carefully monitored in a larger group of patients.

Researchers are also studying povetacicept for other autoimmune diseases. Ongoing research suggests it has a safety profile that warrants further investigation. This information might help prospective participants feel more informed about the treatment's safety record. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Povetacicept is unique because it targets specific immune pathways involved in autoimmune kidney diseases, such as IgA nephropathy (IgAN) and primary membranous nephropathy (pMN). Unlike standard treatments that primarily focus on symptom management or broad immunosuppression, povetacicept acts on the BAFF and APRIL pathways, which play a critical role in the survival and function of B cells responsible for the autoimmune response. This targeted approach offers the potential for more precise treatment with fewer side effects, which is why researchers are excited about its potential to change the landscape of therapy for these conditions.

What evidence suggests that povetacicept might be an effective treatment for autoimmune kidney diseases?

Research has shown that povetacicept, the investigational treatment in this trial, may help treat autoimmune kidney diseases. In previous studies, patients with primary membranous nephropathy (pMN) experienced positive results, suggesting it might benefit similar conditions. For IgA nephropathy (IgAN), povetacicept proved safe and reduced protein levels in urine by 60%, which benefits kidney health. These findings suggest povetacicept could also help with conditions like lupus nephritis and ANCA-associated vasculitis. Although more research is needed, early results appear promising. ^{1 3 5 6 7}

Who Is on the Research Team?

Jiahua Li, M.D.

Principal Investigator

Alpine Immune Sciences, Inc.

Are You a Good Fit for This Trial?

Adults with certain autoimmune kidney diseases like IgA nephropathy, membranous nephropathy, or lupus-related kidney disease can join. They must have a confirmed diagnosis through biopsy and meet specific criteria including protein levels in urine and antibody presence. Stable immunosuppression treatment is required for some conditions before starting the trial.

Inclusion Criteria

I was diagnosed with IgA nephropathy less than 10 years ago and have a UPCR of 0.5 or higher without any immunosuppression treatments.

Indication-specific criteria:

AAV: Past diagnosis of renal AAV, defined as either of the following: History of renal biopsy consistent with renal AAV. History of clinically diagnosed renal AAV. Myeloperoxidase (MPO)-ANCA or proteinase 3 (PR3)-ANCA positive by enzyme-linked immunosorbent assay at screening. At least 4 weeks since initiation of AAV induction therapy, if applicable. On maximal dose or the maximally tolerated dose ACEis/ARBs for ≥12 weeks prior to study Day 1

Exclusion Criteria

I have been diagnosed with another kidney disease.

My kidney function is severely reduced.

I have not had a serious infection recently or ongoing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive povetacicept approximately every 4 weeks for 6 months

24 weeks

6 visits (in-person)

Treatment Extension

Participants may continue treatment for an additional 6 months

24 weeks

Optional Treatment Extension

Participants may opt into an additional 52-week treatment extension

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Povetacicept

Trial Overview The study tests povetacicept (ALPN-303) to see if it's safe and effective for treating autoimmune kidney diseases. Participants will receive doses every four weeks for six months, with an option to continue for another six months.

How Is the Trial Designed?

Group I: Povetacicept Experimental Treatment 1 Intervention

Part A: Participants will receive povetacicept for 24 weeks with the possibility of participating in treatment extensions through 104 weeks of treatment. Part B: Participants with IgAN and pMN will receive povetacicept for an additional 52 weeks.

Who Is Running the Clinical Trial?

Alpine Immune Sciences, Inc.

Lead Sponsor

Trials

9

Recruited

770+

Published Research Related to This Trial

In a study of 159 patients with type 2 diabetic nephropathy, the combination of dipeptidyl peptidase-4 inhibitors (DPP4i) and angiotensin receptor blockers (ARBs) resulted in a slower decline in kidney function (eGFR) compared to ARBs alone after 12 months.

The combined treatment also led to a greater reduction in proteinuria over 24 months, indicating enhanced renoprotection that was independent of changes in blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renoprotection Provided by Dipeptidyl Peptidase-4 Inhibitors in Combination with Angiotensin Receptor Blockers in Patients with Type 2 Diabetic Nephropathy. Qiu, DD., Liu, J., Shi, JS., et al.[2022]

A new monoclonal antibody against Dipeptidyl peptidase IV (DPPIV) effectively suppressed proteinuria and mesangial proliferation in Wistar rats with immune complex-mediated glomerulonephritis, indicating DPPIV's potential role in this condition.

The study suggests that DPPIV regulates the complement cascade, and inhibiting it could be a promising strategy for preventing tissue injury related to complement activation, as shown by the inactivation of the complement cascade in treated rats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Involvement of dipeptidyl peptidase IV in immune complex-mediated glomerulonephritis. Shinosaki, T., Kobayashi, T., Kimura, K., et al.[2023]

The study found that injecting an antibody against dipeptidyl peptidase IV (DPPIV) in rats led to significant proteinuria, indicating that this antibody directly affects glomerular cells and disrupts their function.

The results suggest that the proteinuria is caused by the binding of the anti-DPPIV antibody to the DPPIV present on glomerular cell membranes, rather than serum DPPIV, highlighting a specific mechanism of action in the development of kidney-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proteinuria induced by anti-dipeptidyl peptidase IV (gp108); role of circulating and glomerular antigen. Natori, Y., Shindo, N., Natori, Y.[2019]

In a mouse model of chronic graft-versus-host disease, a significant reduction in Dipeptidyl peptidase IV (DPP IV) enzyme activity was observed as early as 4 weeks post-induction, indicating a potential early biomarker for kidney damage.

The impairment of DPP IV function may contribute to structural and functional kidney lesions, such as albuminuria and podocyte effacement, suggesting that targeting DPP IV could be a therapeutic strategy in lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redistribution of glomerular dipeptidyl peptidase type IV in experimental lupus nephritis. Demonstration of decreased enzyme activity at the ultrastructural level. van Leer, EH., Bruijn, JA., Prins, FA., et al.[2010]

DPP-4 inhibitors, like alogliptin, can reduce inflammation in the kidneys by decreasing the number of inflammatory macrophages, which may help in treating kidney diseases even in non-diabetic conditions.

The study suggests that the anti-inflammatory effects of DPP-4 inhibitors may work through glucagon-like peptide-1 signaling, indicating a potential new mechanism for their use in kidney disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-inflammatory role of DPP-4 inhibitors in a nondiabetic model of glomerular injury. Higashijima, Y., Tanaka, T., Yamaguchi, J., et al.[2018]

Citations

1. journals.lww.com journals.lww.com/jasn/fulltext/2024/10001/updated_results_with_povetacicept,_an_enhanced.913.aspx

Updated Results with Povetacicept, an Enhanced Dual... In these initial findings, povetacicept demonstrates promising activity in pMN, strongly supporting its further development in autoantibody-associated ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06564142

NCT06564142 | Evaluation of Efficacy of Povetacicept in ... The purpose of this study is to evaluate the efficacy of povetacicept in adult participants compared with placebo in reducing proteinuria and preserving renal ...

3. biospace.com biospace.com/alpine-immune-sciences-shares-updated-clinical-data-from-povetacicept-in-iga-nephropathy

Alpine Immune Sciences Shares Updated Clinical Data ... Povetacicept is in development for multiple autoimmune diseases, including IgA nephropathy and other autoimmune kidney diseases, systemic lupus ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05732402

NCT05732402 | An Open-label Study of Povetacicept in ... The goal of this clinical study is to evaluate multiple dose levels of povetacicept in adults with immunoglobulin A (IgA) nephropathy (IgAN), ...

5. docwirenews.com docwirenews.com/post/latest-clinical-data-on-povetacicept-for-igan-will-be-presented-at-wcn

Latest Clinical Data on Povetacicept for IgAN Will Be ... Zigakibart was well tolerated and cut proteinuria by 60% while stabilizing kidney function in IgAN patients over 100 weeks. Read More.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11532938/

A first‐in‐human, randomized study of the safety ... These results, coupled with initial safety and tolerability data, support further clinical evaluation of povetacicept in autoimmune/inflammatory ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2468024923002012

WCN23-0466 PHASE 1 STUDY IN HEALTHY ADULTS OF ... Therapeutic agents targeting BAFF and/or APRIL have demonstrated promising clinical potential in autoantibody-related glomerulonephritides (GN) such as lupus ...