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

476 Participants Needed

Trial Summary

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.

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 patients with autoimmune diseases. It works by blocking factors that stimulate B cells, which are important in the development of IgA Nephropathy, suggesting it could be effective for this condition. ^{1 2 3 4 5}

Is atacicept generally safe for humans?

Atacicept has been studied in healthy volunteers and patients with conditions like lupus nephritis and systemic lupus erythematosus. These studies suggest that atacicept is generally safe, but as with any medication, there may be side effects, and its safety can vary depending on the individual and the condition being treated. ^{1 2 3 5 6}

How is the drug Atacicept unique in treating IgA Nephropathy?

Atacicept is unique because it targets B cells by blocking two specific proteins, BLyS and APRIL, which are involved in the immune system's overactivity in IgA Nephropathy. This approach is different from other treatments that may not specifically target these proteins. ^{1 2 3 4 7}

What is the purpose of this trial?

The purpose of this study is to collect long-term safety and tolerability data for atacicept in patients with IgAN that completed Vera trial investigating atacicept in IgAN population.

Research Team

Zeeshan Khawaja

Principal Investigator

Vice President, Clinical Development

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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]

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]