Long-Term Safety and Efficacy Evaluation of Atacicept in Patients with IgA Nephropathy Following Completion of Parent Study Treatment Period
- Trial ID
- 2024-516380-81-00
- Protocol
- VT-001-0051
- Sponsor
- Vera Therapeutics Inc.
Trial statistics
Objectives
The primary objective of this study is to evaluate the **long-term safety** and tolerability of atacicept in participants who have completed the protocol-defined treatment period in a parent study. This is clinically relevant as it aims to ensure the continued safety of atacicept, a therapeutic agent used in the treatment of IgA nephropathy (IgAN), a condition characterized by the deposition of IgA in the glomeruli, leading to kidney damage.
Secondary objectives include:
- To evaluate the effect of atacicept on change in **proteinuria**, which is a key indicator of kidney function and damage.
- To assess the impact of atacicept on the change in estimated **glomerular filtration rate (eGFR)** using serum creatinine and cystatin C, which are critical measures of kidney function.
- To determine the effect of atacicept on **hematuria**, another important marker of kidney health.
- To evaluate the effect of atacicept on serum **galactose-deficient IgA1 (Gd-IgA1)** levels, which are implicated in the pathogenesis of IgAN.
Participants
The clinical trial involves a total of **50 participants** who have completed the protocol-defined treatment period in a parent study for the treatment of **IgA nephropathy (IgAN)**. The study population includes both male and female subjects, with age categories ranging from adolescents to adults. Participants were selected based on their completion of the prior treatment period and their ability to provide informed consent. The trial includes individuals with a systolic blood pressure of ≤150 mmHg and diastolic blood pressure of ≤90 mmHg at screening and Day 1, specifically for the Atacicept Drug Holiday Group. Female participants are required to not be pregnant or breastfeeding and must adhere to effective contraceptive methods if of childbearing potential. The trial also considers vulnerable populations, ensuring comprehensive safety and tolerability assessments of atacicept in this diverse group.
Plans and Procedures
The clinical trial is designed to evaluate the long-term safety and efficacy of **atacicept** in participants who have completed a prior study involving the treatment of **IgA nephropathy (IgAN)**. This is a Phase 4, multicenter, rollover study that employs a randomized, double-blind, controlled methodology. The trial is expected to commence recruitment on February 1, 2025, and conclude by April 30, 2028. Participants will receive **atacicept** via subcutaneous injection, with a maximum daily dose of 150 mg and a total dose not exceeding 23,400 mg over a treatment period of up to 156 weeks.
The study involves several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as completion of the parent study and specific health parameters. Participants will undergo routine clinical and laboratory assessments to monitor safety and tolerability, as well as secondary endpoints like changes in proteinuria, estimated glomerular filtration rate, hematuria levels, and serum Gd-IgA1 levels. Follow-up visits will be scheduled at regular intervals to ensure ongoing evaluation of these parameters. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted.
Participant involvement is expected to last for the duration of the treatment period, approximately 156 weeks, unless early termination is warranted. Conditions that may lead to early withdrawal include adverse events, non-compliance with study procedures, or withdrawal of consent. The trial aims to provide comprehensive data on the long-term use of **atacicept** in the management of **IgAN**, contributing valuable insights into its safety profile and therapeutic efficacy.
Treatment
The clinical trial involves the administration of **Atacicept**, an experimental medication formulated as a **solution for injection in a pre-filled syringe**. The active substance, atacicept, is a protein-based therapeutic agent. The pharmaceutical form is specifically designed for **subcutaneous use**. The maximum daily dose of atacicept is 150 mg, with a total maximum dose of 23,400 mg over the course of the study. The treatment period extends up to 156 weeks. The atacicept solution is provided in a pre-filled syringe, utilizing a BD Hypak™ SCF™ Barrel Glass barrel with a staked needle (27G ½”) and a Rigid Needle Shield BD260, along with a BD SCF™ Stopper 1ml long W4023 Flurotec. This configuration ensures ease of administration and compliance with dosing schedules.
In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the long-term safety and efficacy of atacicept. Participant compliance with the dosing regimen is monitored throughout the trial to ensure adherence to the prescribed treatment protocol. The trial is designed to assess the safety and tolerability of atacicept in participants who have completed a protocol-defined treatment period in a parent study, thereby providing valuable data on its long-term use.
Efficacy
The efficacy of **Atacicept** in the clinical trial will be assessed through several secondary endpoints. These include evaluating changes in proteinuria, which will be measured using the urine protein-to-creatinine ratio (UPCR) and urine albumin-to-creatinine ratio (UACR) on spot urine samples. Additionally, changes in the estimated glomerular filtration rate (eGFR) will be assessed based on serum creatinine and cystatin C levels. Hematuria levels will be evaluated using a urine dipstick to detect blood in the urine. Furthermore, changes in serum Gd-IgA1 levels will be monitored as part of the efficacy assessment.
Inclusion and Exclusion Criteria
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.
- For Atacicept Drug Holiday Group only: Systolic blood pressure ≤150 mmHg and diastolic blood pressure ≤90 mmHg at screening and Day 1.
- A participant who was assigned female at birth is eligible if not pregnant (ie, after a confirmed menstrual period, a negative serum pregnancy test at screening and has a negative urine pregnancy test at Day 1), is not breastfeeding (for at least three months prior to screening), and at least one of the following conditions applies: *Is not a woman of childbearing potential (WOCBP) OR *Is a WOCBP who agrees to use a highly effective contraceptive method (ie, has a failure rate of less than 1% per year) at least 7 days prior to enrollment, through 175 days after the last dose of study drug.
- For Atacicept Drug Holiday Group only: eGFR ≥ 20 mL/min/1.73 m2 at screening, as per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
- For Atacicept Drug Holiday Group only: On a stable prescribed regimen of renin-angiotensin-aldosterone system inhibitor (ACEi or ARB) per guidance and local standard of care that is at the maximum labeled or tolerated dose at screening and from screening to study Day 1.
Exclusion Criteria
- For Group 1 Atacicept Drug Holiday: Evidence of rapidly progressive glomerulonephritis (loss of ≥50% of eGFR within 3 months of screening).
- For Group 1 Atacicept Drug Holiday: Evidence of nephrotic syndrome (serum albumin <30g/L in association with UPCR >3.5 mg/mg) within 6 months of screening.
- For Group 1 Atacicept Drug Holiday: Currently on chronic dialysis, or expected to initiate dialysis within 12 weeks of screening.
- For Group 1 Atacicept Drug Holiday: Renal or other organ transplantation prior to, or expected during, the study, with the exception of corneal transplants.
- For Group 1 Atacicept Drug Holiday: Prohibited medications: • Use of systemic corticosteroids (including oral budesonide) or immunosuppressive medications (eg, MMF, azathioprine, cyclophosphamide, hydroxychloroquine) for the treatment of IgAN within 2 months prior to Screening • For glucocorticosteroids (GCS), “Systemic” is defined as oral, rectal or injectable (intravenous or intramuscular) routes of administration. Other routes of administration are allowed, including intra-articular, inhaled, topical, ophthalmic, optic and intranasal. • Use of B-cell–directed biologic therapies including belimumab, rituximab, ocrelizumab within 12 months of screening • Use of other biologics (eg, anti-TNF, abatacept, anti-IL-6) and investigational biologics for the treatment of IgAN within 6 months of screening
- For Group 1 Atacicept Drug Holiday: Clinically significant or predefined abnormalities per central laboratory tests at screening, meeting any of the criteria below: - Clinical evidence of immunosuppression and/or hypogammaglobulinemia as determined by the Investigator. - Aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase level >2.5 × upper limit of normal (ULN) or total bilirubin >1.5 x ULN. *If the participant has a known history of Gilberts (history of isolated increase in total bilirubin without increase in liver transaminases), contact the Medical Monitor for further discussion.
- For Group 1 Atacicept Drug Holiday: Administration of live and live-attenuated vaccinations within 30 days prior to enrollment
- For Group 1 Atacicept Drug Holiday: History or current diagnosis of any demyelinating disease such as, but not restricted to, multiple sclerosis (MS) or optic neuritis (ON)
- For Group 1 Atacicept Drug Holiday: Active clinically significant viral, bacterial or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks prior to enrollment, or completion of oral anti-infectives within 2 weeks prior to enrollment, or a history of recurrent infections (ie, 3 or more of the same type of infection in a 12-month rolling period). Vaginal candidiasis, onychomycosis and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled are not exclusionary. • If the participant is undergoing current treatment for latent tuberculosis infection (LTBI), they must have received at least 4 continuous weeks of an appropriate LTBI treatment prior to screening without evidence of re-exposure to be eligible for this study. If on LTBI treatment at the Screening visit, the participant will be expected to complete an appropriate LTBI treatment regimen to remain in the trial. • Participants with current household contacts with active TB will be excluded unless prophylaxis treatment has been completed, and evidence that household contacts have completed treatment is provided. • Evidence of active TB determined by a local laboratory at the Screening Visit. Indeterminate local TB tests may be repeated once by the same test and will be considered positive if retest results are positive or indeterminate.
- For Group 1 Atacicept Drug Holiday: History of acute or chronic infection with human immunodeficiency virus, hepatitis C virus, or hepatitis B virus. • Participants who are positive hepatitis B surface antigen (HBsAg) are excluded • Participants who are HBsAg negative, hepatitis B core antibody (HBcAb) positive, hepatitis B surface antibody (HBsAb) positive with no detectable hepatitis B virus (HBV) DNA are eligible but will require monthly HBV DNA monitoring through safety follow up. • Participants with positive hepatitis C (HCV) RNA are excluded, however participants who are HCV antibody positive with no detectable HCV RNA at least 24 weeks after completion of antiviral therapy are eligible.
- For Group 1 Atacicept Drug Holiday: History of splenectomy.
- For Group 1 Atacicept Drug Holiday: History of malignancy (hematologic or solid tumor) within 5 years prior to Day 1, except adequately treated basal cell or squamous cell carcinomas of the skin (no more than 3 lesions requiring treatment in lifetime) or carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix
- For Group 1 Atacicept Drug Holiday: Known hypersensitivity to atacicept or any component of the formulated atacicept
- For Group 1 Atacicept Drug Holiday: Major surgery within 6 weeks prior to screening or planned/expected major surgery during the study period (including the safety follow-up period) - Major surgery often involves opening one of the major body cavities (abdomen or chest) and/or use of general anesthesia. Types of surgery that have the highest risk include heart or lung, liver, abdomen, or major operations on the bones and joints (eg, hip replacement). Participants with positive hepatitis C (HCV) RNA are excluded, however participants who are HCV antibody positive with no detectable HCV RNA at least 24 weeks after completion of antiviral therapy are eligible.
- For Group 1 Atacicept Drug Holiday: Clinically significant history of alcohol or drug abuse in the 1 year prior to Day 1 as per Investigator opinion
- For Group 1 Atacicept Drug Holiday: Unwillingness or lack of capacity to follow all study procedures
- For Group 1 Atacicept Drug Holiday: Treatment with other investigational agents within the last 4 weeks or 5 half-lives, whichever is longer, prior to screening
- For Group 1 Atacicept Drug Holiday: Total urine protein excretion ≥5g per 24-hour or UPCR ≥5 mg/mg based on a 24-hour urine sample during the Screening Period
- For Group 1 Atacicept Drug Holiday: Uncontrolled diabetes, defined as hemoglobin-A1c (HbA1c) >7.5% at screening
- For Group 2 Continuous Atacicept: Evidence of rapidly progressive glomerulonephritis (loss of ≥50% of eGFR within 3 months of Day 1)
- For Group 2 Continuous Atacicept: Evidence of nephrotic syndrome (serum albumin <30g/L in association with UPCR >3.5 mg/mg) within 6 months of Day 1
- For Group 2 Continuous Atacicept: Currently on chronic dialysis, or expected to initiate dialysis within 12 weeks of Day 1
- For Group 2 Continuous Atacicept: Renal or other organ transplantation prior to, or expected during, the study, with the exception of corneal transplants
- For Group 2 Continuous Atacicept: Clinically significant or predefined abnormalities per central laboratory tests on Day 1 , meeting any of the criteria below: • Clinical evidence of immunosuppression and/or hypogammaglobulinemia as determined by the Investigator
- For Group 2 Continuous Atacicept: Active clinically significant viral, bacterial or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks prior to enrollment, or completion of oral anti-infectives within 2 weeks prior to enrollment, or a history of recurrent infections (ie, 3 or more of the same type of infection in a 12-month rolling period). Vaginal candidiasis, onychomycosis and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled are not exclusionary.
- For Group 2 Continuous Atacicept: Known hypersensitivity to atacicept or any component of the formulated atacicept
- For Group 2 Continuous Atacicept: Clinically significant history of alcohol or drug abuse in the one year prior to Day 1 as per Investigator opinion
- For Group 2 Continuous Atacicept: Unwillingness or lack of capacity to follow all study procedures
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 01 Feb 2025 | 3 |
 Czechia | Recruiting | 01 Feb 2025 | 12 |
 Germany | Recruiting | 01 Feb 2025 | 4 |
 Greece | Recruiting | 01 Feb 2025 | 10 |
 Poland | Recruiting | 01 Feb 2025 | 8 |
 Spain | Recruiting | 01 Feb 2025 | 6 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Atacicept | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS USE | 150 | 156 | PRD10245858 |
Atacicept Autoinjector Combination | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 150 | 156 | PRD12540579 |