Atacicept for IgA Nephropathy

(ORIGIN EXTEND Trial)

Overseen By Vera Therapeutics, Inc. Clinical Trials Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vera Therapeutics, Inc.

Must not be taking: Corticosteroids, Immunosuppressives, B-cell biologics, others

Disqualifiers: Glomerulonephritis, Nephrotic syndrome, Dialysis, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 156 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the long-term safety and patient tolerance of atacicept (an anti-Blys/anti-APRIL fusion protein) for individuals with IgA nephropathy, a kidney disease that can cause kidney damage. It targets those who have completed a previous study with atacicept. Eligible participants have successfully finished the prior study and have their IgA nephropathy under control without an immediate need for dialysis. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as systemic corticosteroids and immunosuppressive drugs, at least 2 months before screening. Additionally, B-cell-directed biologic therapies must be stopped 12 months before screening, and other biologics 6 months before screening.

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

Research has shown that atacicept has generally been well-tolerated in past studies. Some patients experienced side effects, usually mild to moderate. Common side effects included redness or swelling at the injection site, headaches, and some respiratory infections. Most participants found these side effects manageable.

It is important to know that researchers are still studying atacicept to gather more information about its long-term safety. This is a normal part of the process to ensure any potential risks are understood and can be managed. For those considering joining a trial, this information suggests that the treatment has been relatively safe in earlier studies, although ongoing research is needed to confirm these findings.

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for IgA nephropathy, which often include corticosteroids or immunosuppressive drugs, Atacicept offers a fresh approach. Atacicept is unique because it targets and inhibits the activity of specific proteins called B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). These proteins are involved in the production of antibodies, which are believed to play a role in the progression of IgA nephropathy. Researchers are excited about Atacicept because it has the potential to more precisely modulate the immune system, potentially leading to better outcomes with fewer side effects compared to traditional therapies.

What evidence suggests that atacicept might be an effective treatment for IgA nephropathy?

Research has shown that atacicept, the investigational treatment in this trial, may help treat IgA nephropathy, a type of kidney disease. In one study, patients taking atacicept experienced a 46% decrease in protein in their urine, indicating reduced kidney damage. Another study found that atacicept reduced protein in urine by about 40% compared to a placebo. Additionally, atacicept lowered levels of a specific protein linked to disease activity in IgA nephropathy. These findings suggest that atacicept could help manage the condition by protecting the kidneys from further harm. ^{1 2 3 4 5}

Who Is on the Research Team?

Zeeshan Khawaja

Principal Investigator

Vice President, Clinical Development

Are You a Good Fit for This Trial?

This trial is for patients with IgA Nephropathy, a kidney disease, who have completed the Vera trial. It's designed to gather more information on the long-term safety and effects of Atacicept in this specific group.

Inclusion Criteria

Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study assessments

Completed the protocol-defined treatment period on treatment in a parent study of atacicept in patients with IgAN

My blood pressure is 150/90 mmHg or lower.

Exclusion Criteria

I am unable or unwilling to follow the study's procedures.

I haven't taken any experimental drugs in the last 4 weeks or longer.

Clinically significant history of alcohol or drug abuse in the 1 year prior to Day 1 as per Investigator opinion

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atacicept 150 mg once weekly, self-administered subcutaneously. Participants are grouped by whether they are restarting atacicept after a drug holiday or continuing without disruption.

156 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of adverse events, hematuria, proteinuria, eGFR, and serum Gd-IgA1 levels.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atacicept

Trial Overview The study focuses on evaluating the continued use of Atacicept at a dose of 150 mg. The goal is to understand its long-term impact on patients with IgA Nephropathy who previously participated in related research.

How Is the Trial Designed?

Group I: Atacicept 150mg once weekly subcutaneous (SC) injection Experimental Treatment 1 Intervention

Other Names: VT-001

Who Is Running the Clinical Trial?

Vera Therapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

1,200+

Published Research Related to This Trial

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 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]

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]

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 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 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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2510198

A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy In at least 50% of patients, IgA nephropathy leads to kidney failure or death within 10 to 20 years after diagnosis. Atacicept is a native human ...

2. ir.veratx.com ir.veratx.com/news-releases/news-release-details/vera-therapeutics-announces-positive-origin-phase-3-data

News Release Atacicept met the primary endpoint of reduction in proteinuria (UPCR) at week 36; participants receiving atacicept achieved a 46% reduction ...

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

A phase 2b, randomized, double-blind, placebo-controlled ... The safety profile of atacicept was like placebo. Thus, our results provide evidence to support a pivotal, phase 3 study of atacicept in IgA ...

4. journals.lww.com journals.lww.com/jasn/fulltext/2023/11001/atacicept_in_iga_nephropathy__igan___continued.3438.aspx

Atacicept in IgA Nephropathy (IgAN): Continued Protective... Atacicept treatment was associated with continued protective immunity to tetanus and diphtheria in the Ph2a JANUS study.

5. medcentral.com medcentral.com/nephrology/kidney/origin-phase-3-trial-confirms-atacicepts-efficacy-in-igan

ORIGIN Phase 3 Trial Confirms Atacicept's Efficacy in IgAN “Its ability to reduce urinary protein excretion by approximately 40% compared to the placebo, while lowering galactose-deficient IgA1 levels, ...