Atacicept in Subjects With IgA Nephropathy (ORIGIN 3)

Vera Therapeutics

Status and phase: Active, not recruiting; Phase 3

Conditions: Berger Disease; IgA Nephropathy

Treatments: Biological: Atacicept; Other: Placebo to match Atacicept

Study type: Interventional

Funder types: Industry

Identifiers

NCT04716231

VT-001-0050

Details and patient eligibility

About

A Phase 3 Study with Atacicept in Subjects With IgA Nephropathy (ORIGIN 3)

Full description

This is a multi-part study comprising of the original Phase 2b study and the addition of a separate pivotal Phase 3 study.

After the completion of the primary results for the Ph 2b dose ranging study, the pivotal study will evaluate the efficacy and safety of atacicept compared to placebo in reducing proteinuria in subjects with IgAN and persistent proteinuria despite being on a maximally tolerated dose (MTD) of a RASi. Safety, eGFR, serum immunoglobulins and Gd-IgA1 will also be clinically assessed. The clinical study is comprised of a 104wk double-blind treatment period, followed by a 52wk open-label treatment period and a 26wk safety follow-up period. The UPCR primary endpoint will be assessed after the first 200 patients are randomized.

Enrollment: 376 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Must have the ability to understand and sign a written informed consent form
• Male or female of ≥18 years of age
• 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
• Diagnosis of IgAN as demonstrated by renal biopsy conducted within 10 years
• eGFR ≥ 30 mL/min/1.73 m2, as per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
• On a stable prescribed regimen of RAASi for at least 12 weeks that is at the maximum labeled or tolerated dose at Screening
• Systolic blood pressure ≤150 mmHg and diastolic blood pressure ≤90 mmHg

Key Exclusion Criteria:

• 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
• 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 the Screening Period
• Evidence of rapidly progressive glomerulonephritis (loss of ≥ 50% of eGFR within 3 months of screening)
• Evidence of nephrotic syndrome within 6 months of screening (serum albumin <30g/L in association with UPCR >3.5 mg/mg
• Renal or other organ transplantation prior to, or expected during the study
• Concomitant chronic renal disease in addition to IgAN
• Uncontrolled diabetes, defined as hemoglobin-A1c (HbA1c) >7.5% at screening
• History of tuberculosis (TB), untreated latent TB infection (LTBI), or evidence of active TB determined by a positive Quantiferon test
• Participation in the Phase 2b (Parts A and B) study or any previous treatment with atacicept

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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376 participants in 2 patient groups, including a placebo group

Atacicept Dose 150mg

Experimental group

Description:

Atacicept 150mg once weekly subcutaneous (SC) injections

Treatment:

Biological: Atacicept

Placebo to match Atacicept (Part C/D)

Placebo Comparator group

Description:

Placebo to match Atacicept once weekly subcutaneous (SC) injection

Treatment:

Other: Placebo to match Atacicept