Atacicept for IgA Nephropathy

(ORIGIN 3 Trial)

Not currently recruiting at 82 trial locations

Overseen By Vera Therapeutics, Inc. Clinical Trials Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Vera Therapeutics, Inc.

Must be taking: RAASi

Disqualifiers: Secondary IgAN, Nephrotic syndrome, Uncontrolled diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called atacicept for individuals with IgA nephropathy, a kidney condition that can cause blood and protein in the urine. The trial aims to determine if weekly injections of atacicept can reduce these symptoms. Some participants will receive a placebo, a harmless substance resembling the treatment, to compare results. Individuals with IgA nephropathy, confirmed by a kidney biopsy and with protein levels in their urine above a certain threshold, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable regimen of RAASi (a type of blood pressure medication) for at least 12 weeks before starting. The protocol does not specify if you need to stop other medications, so it's best to discuss with the trial team.

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

Research has shown that atacicept is generally safe for people with IgA nephropathy. In one study, the side effects of atacicept matched those of a placebo, an inactive treatment. Another study observed atacicept over 96 weeks and found it safe for long-term use. Although some participants experienced infections, no major safety concerns arose. Overall, these findings support the safety of atacicept for potential participants. ^{1 2 3 4 5}

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

Unlike the standard of care for IgA Nephropathy, which typically includes treatments like corticosteroids and blood pressure medications, Atacicept acts on a different biological pathway. Atacicept is unique because it targets the activity of B lymphocytes, which are cells involved in the production of antibodies that can damage the kidneys. This targeted approach may offer a more precise intervention compared to traditional therapies that broadly suppress the immune system. Researchers are excited about Atacicept because its mechanism could potentially reduce kidney damage while minimizing side effects associated with broader immunosuppressive treatments.

What evidence suggests that Atacicept might be an effective treatment for IgA Nephropathy?

Studies have shown that atacicept looks promising for treating IgA nephropathy, a kidney disease. Research indicates that atacicept can reduce key disease markers, such as a specific protein linked to the condition and blood in the urine, over an extended period. In this trial, participants will receive either atacicept or a placebo. In previous studies, patients taking atacicept demonstrated improvements in protein levels in their urine and kidney function over 96 weeks. These results suggest that atacicept could effectively manage symptoms of IgA nephropathy and slow the disease's progression. ^{1 2 3 4 6}

Who Is on the Research Team?

Zeeshan Khawaja

Principal Investigator

Vice President, Clinical Development

Are You a Good Fit for This Trial?

Adults (18+) with IgA Nephropathy, a kidney disease, who have not responded well to standard treatments can join. They must have had a biopsy confirming the diagnosis within the last 10 years and stable blood pressure. People with related conditions like lupus or those with very severe kidney issues, uncontrolled diabetes, or past tuberculosis are excluded.

Inclusion Criteria

My kidney biopsy within the last 10 years confirmed I have IgAN.

Your kidney function is good, with an eGFR of at least 30 mL/min/1.73 m2.

Your urine shows a high amount of protein, more than 1.0 gram in a 24-hour period, or a high protein to creatinine ratio.

Exclusion Criteria

Your diabetes is not well controlled, with a hemoglobin-A1c (HbA1c) level above 7.5%.

You have had a specific kidney condition called nephrotic syndrome in the past 6 months.

I have previously participated in the Phase 2b study or received atacicept.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive either atacicept or placebo in a double-blind manner to evaluate efficacy and safety in reducing proteinuria

104 weeks

Weekly subcutaneous injections

Open-label Treatment

Participants receive open-label atacicept treatment to further assess safety and efficacy

52 weeks

Weekly subcutaneous injections

Safety Follow-up

Participants are monitored for safety and effectiveness after treatment

26 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atacicept

Trial Overview

The trial is testing Atacicept against a placebo in patients with IgA Nephropathy. It's designed to see if Atacicept can help manage the condition better than no active treatment. Participants will be randomly assigned to receive either Atacicept or an inactive substance that looks the same.

How Is the Trial Designed?

Group I: Atacicept Dose 150mg Experimental Treatment 1 Intervention

Atacicept 150mg once weekly subcutaneous (SC) injections

Group II: Placebo to match Atacicept (Part C/D) Placebo Group 1 Intervention

Placebo to match Atacicept once weekly subcutaneous (SC) injection

Who Is Running the Clinical Trial?

Vera Therapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

1,200+

Published Research Related to This Trial

Atacicept was found to be well tolerated in a phase I study involving 24 healthy Japanese subjects, with no severe adverse events reported, indicating a favorable safety profile across different ethnicities.

The pharmacokinetics of atacicept were comparable between Japanese and Caucasian subjects, showing similar exposure levels and dose-response relationships, which suggests that atacicept may be effective in diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Atacicept in a Randomized Trial in Healthy Caucasian and Japanese Subjects. Willen, D., Uhl, W., Wolna, P., et al.[2022]

Atacicept was well tolerated in a Phase I study involving 23 healthy male volunteers, with no significant adverse effects or changes in vital signs, indicating a good safety profile for this potential treatment.

The study demonstrated that atacicept has a dose-dependent biological effect on IgM levels, suggesting its efficacy in modulating B-cell activity, with effects lasting up to 210 days post-dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics and pharmacodynamics of atacicept in healthy volunteers. Munafo, A., Priestley, A., Nestorov, I., et al.[2022]

The APRIL-LN study was a Phase II/III trial evaluating atacicept in patients with active lupus nephritis, but it was terminated early after enrolling only six patients due to significant declines in serum immunoglobulin G (IgG) levels and serious infections, including pneumonia.

Atacicept treatment led to a substantial drop in IgG levels and increased proteinuria, indicating potential safety concerns that need to be addressed in future studies before assessing its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. Ginzler, EM., Wax, S., Rajeswaran, A., et al.[2023]

Telitacicept is a promising dual-target biological agent that inhibits B cell activating factors (BAFF) and APRIL, which are crucial in the autoimmune pathways associated with IgA nephropathy (IgAN).

By improving renal immune complex function and reducing symptoms like hematuria and proteinuria, telitacicept shows potential for treating IgAN and other autoimmune diseases linked to B cell activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of telitacicept in the treatment of IgA nephropathy. Wu, L., Du, X., Lu, X.[2023]

Atacicept, a drug designed to inhibit B cell growth factors, showed consistent pharmacokinetics and biological activity in patients with systemic lupus erythematosus across different doses and administration routes (intravenous and subcutaneous).

The drug demonstrated approximately 30-40% bioavailability regardless of the administration method, suggesting that both routes can be effectively used in future treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and immunoglobulin response of subcutaneous and intravenous atacicept in patients with systemic lupus erythematosus. Nestorov, I., Papasouliotis, O., Pena Rossi, C., et al.[2018]

Atacicept, a B-cell-targeted immunomodulator, demonstrated an acceptable safety profile in a phase II study involving 16 patients with IgA nephropathy, with most treatment-emergent adverse events being mild or moderate.

The treatment led to significant reductions in pathogenic Gd-IgA1 levels and early improvements in proteinuria, while renal function remained stable compared to a decline observed in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II JANUS Study of Atacicept in Patients With IgA Nephropathy and Persistent Proteinuria. Barratt, J., Tumlin, J., Suzuki, Y., et al.[2022]

Telitacicept is a novel treatment that targets BAFF and APRIL, two proteins crucial for B cell maintenance and function, and has been approved in China for treating systemic lupus erythematosus.

The drug is currently undergoing clinical trials for other autoimmune diseases, highlighting its potential efficacy in managing conditions linked to B cell overactivity, such as lupus nephritis and IgA nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Telitacicept for autoimmune nephropathy. Cai, J., Gao, D., Liu, D., et al.[2023]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39462308/

Long-Term Results from an Open-Label Extension Study of ...

This study evaluated the long-term efficacy and safety of atacicept in patients with IgA nephropathy over 96 weeks. Methods: Participants ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38552841/

A phase 2b, randomized, double-blind, placebo-controlled ...

To compare efficacy and safety of atacicept versus placebo in patients with IgAN, this randomized, double-blind, placebo-controlled phase 2b ...

3.

journals.lww.com

journals.lww.com/jasn/fulltext/2025/04000/long_term_results_from_an_open_label_extension.15.aspx

Long-Term Results from an Open-Label Extension Study of...

This study evaluated the long-term efficacy and safety of atacicept in patients with IgA nephropathy over 96 weeks.

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S2468024924024264

WCN25-2470 Long-term Results from the ORIGIN Phase ...

Key efficacy outcomes were changes in galactose-deficient IgA1 (Gd-IgA1), percentage of participants with hematuria, UPCR, and eGFR over 96 weeks. Long-term ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02808429

Efficacy and Safety of Atacicept in IgA Nephropathy

This main purpose of this study was to evaluate the safety, tolerability, dose response and efficacy of Atacicept in participants with IgA nephropathy and ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S2468024924003644

WCN24-342 ATACICEPT IN IGA NEPHROPATHY

In ORIGIN, safety data on infections were analyzed by treatment arm up to 36 weeks. Results. The JANUS population was 50% male with baseline median age 44; the ...