A Phase 3 clinical trial of Atacicept in Subjects with IgA Nephropathy
- Conditions
- Health Condition 1: N29- Other disorders of kidney and ureter in diseases classified elsewhere
- Registration Number
- CTRI/2023/11/059398
- Lead Sponsor
- Vera Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
1. Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study assessments.
2. Adult male or female of =18 years of age and =70 years, or as per country specific legally or nationally recognized adult age, who provide written informed consent prior to performing any study assessments.
3. Diagnosis of IgAN as demonstrated by renal biopsy conducted within 10 years of the Screening Visit.
4. Total urine protein excretion =1.0 g per 24-hour or urine protein to creatinine ratio (UPCR) =1.0 mg/mg based on a 24-hour urine sample during the Screening Period
5. eGFR =30 mL/min/1.73 m2 at screening, as per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
6. On a stable prescribed regimen of RASi (ACEi or ARB) for at least 12 weeks that is at the maximum labeled or tolerated dose at screening and from screening to study Day 1.
a.The subject is eligible if they do not tolerate RASi, provided their management of IgAN is standard of care (SoThe subject is eligible if they do not tolerate RASi, provided their management of IgAN is standard of care (SoC) per local practice. This intolerance must be documented by the Investigator and discussed with the medical monitor.
7. Systolic blood pressure =150 mmHg and diastolic blood pressure =90 mmHg at screening
8. A female is eligible if she is not pregnant (i.e., after a confirmed menstrual period, a negative serum pregnancy test at screening and negative urine pregnancy test at Day 1), not breastfeeding (for at least 3 months prior to screening), and at least one of the following conditions applies:
a. Is not a woman of childbearing potential (WOCBP)
b. Is a WOCBP who agrees to use a highly effective contraceptive method (i.e., has a failure rate of less than 1% per year), at least 7 days prior to randomization, through 175 days after the last dose of study drug.
1. Participation in the Phase 2b (Parts A and B) study or any previous treatment with atacicept
2. IgAN secondary to another condition (e.g., liver cirrhosis), or other causes of mesangial IgA deposition including IgA vasculitis (i.e., Henoch-Schonlein purpura), systemic lupus erythematosus (SLE), dermatitis herpetiformis, ankylosing spondylitis
3. Evidence of rapidly progressive glomerulonephritis (loss of = 50% of eGFR within 3 months of screening)
4. Evidence of nephrotic syndrome within 6 months of screening (serum albumin <30g/L in association with UPCR >3.5 mg/mg)
5. Renal or other organ transplantation prior to, or expected during, the study, with the exception of corneal transplants.
6. Concomitant chronic renal disease in addition to IgAN (e.g., diabetic nephropathy, primary focal segmental glomerulosclerosis (FSGS), membranous nephropathy, C3 glomerulopathy, lupus nephritis)
7. Uncontrolled diabetes, defined as hemoglobin-A1c (HbA1c) >7.5% at screening
8. History of tuberculosis (TB), untreated latent TB infection (LTBI), or evidence of active TB determined by a positive Quantiferon test at the Screening Visit.
If the subject is undergoing current treatment for LTBI, they must have received at least 4 continuous weeks of an appropriate LTBI treatment prior to the Screening Visit without evidence of re-exposure to be eligible for this study. If on LTBI treatment at the Screening Visit, the subject will be expected to complete an appropriate LTBI treatment regimen to remain in the trial.
a. Subjects 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.
b. Indeterminate Quantiferon tests may be repeated once by the same test and will be considered positive if retest results are positive or indeterminate.
9. Prohibited medications:
Use of systemic corticosteroids (including oral budesonide) for the treatment of IgAN within 6 months prior to screening, from screening to Day 1 or expected use during the study.
• 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, otic and intranasal.For non-IgAN indications (e.g., gout flare, exacerbation of asthma, severe rash, etc.):
- Within 12 weeks prior to randomization: Use of systemic corticosteroids or immunosuppressive medications for >1 week or average dose >0.5 mg/kg/day prednisolone or equivalent
• Immunosuppressive medications (e.g., MMF, azathioprine, cyclophosphamide, hydroxychloroquine) for the treatment of IgAN within 12 weeks prior to screening, from screening to Day1 or expected use during the study.
• Use of traditional Chinese medications and/or Ayurvedic medications within 12 weeks prior to screening or from screening to Day 1
• Use of B-cell–directed biologic therapies including but not limited to belimumab, rituximab, ocrelizumab for any period of time
• Use of other biologics (e.g., anti-TNF, abatacept, anti-IL-6) and investigational biologics for any period of time
• Use of endothelin receptor antagonists (ERAs) for any period of time
10. Clinically significant or predefined abnormalities per central laboratory
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Evaluate the effect of atacicept compared to placebo on change in proteinuria in adult subjects with IgANTimepoint: 36 weeks
- Secondary Outcome Measures
Name Time Method Evaluate the effect of atacicept on annualized rate of change in estimated glomerular filtration rate (eGFR)Timepoint: Through Week 104