Atacicept for IgA Nephropathy

(ORIGIN 3 Trial)

Recruiting in Palo Alto (17 mi)

+82 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Vera Therapeutics, Inc.

Must be taking: RAASi

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

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called atacicept for people with a kidney disease called IgA Nephropathy who still have too much protein in their urine despite other treatments. Atacicept works by calming the immune system to help reduce protein levels in the urine. The study will compare atacicept to see if it is effective and safe.

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.

What data supports the effectiveness of the drug Atacicept for IgA Nephropathy?

Atacicept is a drug that targets B cells, which are part of the immune system, and has been shown to reduce immunoglobulin levels in autoimmune diseases. It blocks factors that stimulate B cells, which are important in the development of IgA Nephropathy, suggesting it could help manage this condition. ^{1 2 3 4 5}

Is atacicept safe for humans?

Atacicept has been studied in healthy volunteers and patients with conditions like lupus nephritis and systemic lupus erythematosus. These studies generally found it to be safe, but some trials were stopped early, indicating that more research is needed to fully understand its safety profile. ^{1 2 3 5 6}

How is the drug Atacicept unique in treating IgA nephropathy?

Atacicept is unique because it targets and blocks two specific proteins, BLyS and APRIL, which are involved in the activation of B cells (a type of immune cell) that play a role in autoimmune diseases like IgA nephropathy. This dual-target approach helps reduce the immune response that contributes to kidney damage in this condition. ^{1 2 3 4 7}

Research Team

Zeeshan Khawaja

Principal Investigator

Vice President, Clinical Development

Eligibility Criteria

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.

I am 18 years old or older.

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Atacicept (Biological Response Modifier)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

Randomized Phase II JANUS Study of Atacicept in Patients With IgA Nephropathy and Persistent Proteinuria. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics and pharmacodynamics of atacicept in healthy volunteers. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Role of telitacicept in the treatment of IgA nephropathy. [2023]

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

Pharmacokinetics and immunoglobulin response of subcutaneous and intravenous atacicept in patients with systemic lupus erythematosus. [2018]

6. France pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Atacicept in a Randomized Trial in Healthy Caucasian and Japanese Subjects. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Telitacicept for autoimmune nephropathy. [2023]