IgA Nephropathy MedDRA version: 20.0 Level: PT Classification code 10021263 Term: IgA nephropathy System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: Atacicept
Product Code: VT-001
Pharmaceutical Form: Solution for infusion in pre-filled syringe
INN or Proposed INN: Atacicept
CAS Number: 845264-92-8
Other descriptive name: ATACICEPT
C
Sponsors
Vera Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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, 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 > 0.75g per 24-hour or UPCR > 0.75 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 RAASi for at least 12 weeks that is at the maximum labeled or tolerated dose at screening. • The subject is eligible if they do not tolerate RAASi, provided their management of IgAN is SoC according to local guidelines. This must be documented by the Investigator. 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: • Is not a woman of childbearing potential (WOCBP). OR • Is a WOCBP who agrees to use a highly effective contraceptive method (i.e., has a failure rate of less than 1% per year), as listed in Appendix 2, at least 7 days prior to randomization through 175 days after the last dose of study drug. See Appendix 2 for further details. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. IgAN secondary to another condition (e.g., liver cirrhosis), or other causes of mesangial IgA deposition including IgA vasculitis (i.e., Henoch-Schonlein purpura), SLE, dermatitis herpetiformis, ankylosing spondylitis 2. Evidence of rapidly progressive glomerulonephritis (loss of = 50% of eGFR within 3 months of screening 3. Evidence of nephrotic syndrome within 6 months of screening (serum albumin 3.5 mg/mg 4. Total urine protein excretion = 5g per 24-hour or urine protein to creatinine ratio (UPCR) = 5 mg/mg based on a 24-hour urine sample during Screening 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. 9. Prohibited medications: • Use of systemic corticosteroids or immunosuppressive medications (e.g., MMF, azathioprine, cyclophosphamide, hydroxychloroquine) for the treatment of IgAN within 3 months prior to screening or expected use during the study. • For non-IgAN indications (e.g., gout flare, exacerbation of asthma, severe rash, etc): • Within 3 months prior to randomization: Use of systemic corticosteroids or immunosuppressive medications for > 1 week or 0.5 mg/kg/day prednisolone or equivalent • Use of B-cell–directed biologic therapies including blisibimod, belimumab, rituximab, ocrelizumab for any period of time • Use of other biologics (e.g., anti-TNF, abatacept, anti-IL-6) and investigational biologics 10. Clinically significant or predefined abnormalities per central laboratory tests, at the Screening Visit, meeting any of the criteria below: • serum IgG below 7 g/L • aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase level > 2.5 × upper limit of normal (ULN) or total bilirubin >1.5 x ULN. i. If subject 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. 11. Administration of a live and live-attenuated vaccinations within 30 days prior to randomization 12. History or current diagnosis of any demyelinating disease such as, but not restricted to, multiple sclerosis (MS) or optic neuritis (ON) 13. Patients with history of unstable angina, Class III and IV congestive heart failure and/or clinically significant arrhythmia, as judged by the Investigator. 14. Any condition, including any uncontrolled disease state other than IgAN, that in the opinion of the Investigator or the Sponsor/designee constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct or evaluation 15. 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, or during the Screening Visit, or completion of oral anti-infectives within 2 weeks prior to, or during the Screening Visit or a history of recurrent infections (i.e., 3 or more of the same t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the effect of atacicept compared to placebo on change in proteinuria in adult subjects with IgAN;Secondary Objective: - Evaluate the effect of atacicept compared to placebo on change in proteinuria in adult subjects with IgAN - Evaluate the effect of atacicept on change in proteinuria in adult subjects with IgAN - Evaluate the effect of atacicept on rate of change in estimated glomerular filtration rate (eGFR) - Evaluate the effect of atacicept on change in serum immunoglobulin levels, complement levels and on serum Gd-IgA1 levels - Evaluate the safety and tolerability of atacicept - Evaluate serum PK of atacicept ;Primary end point(s): Urine protein to creatinine ratio (UPCR);Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Urine protein to creatinine ratio (UPCR) - Urine protein to creatinine ratio (UPCR) - Rate of change in eGFR - IgA, IgG, IgM levels, C3 and C4 levels. Gd-IgA1 levels - Routine clinical and laboratory tests, and AEs - Serum concentration of atacicept;Timepoint(s) of evaluation of this end point: - Week 36 - Weeks 12, 48 and 96 - Weeks 12, 24, 36, 48 and 96 - Weeks 12, 24, 36, 48, 96 and Follow Up Weeks 12 and 26 - Entire Study - Entire Study | — |
Countries
Australia, Belgium, Canada, Czechia, Czech Republic, Germany, Greece, India, Korea, Republic of, Malaysia, Poland, Turkey, United Kingdom, United States
Contacts
Public ContactRegulatory
Vera Therapeutics, Inc.
Outcome results
None listed