Atacicept in Subjects With IgA Nephropathy (ORIGIN 3)

A Phase 2b/3, Multi-part, Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Atacicept in Subjects With IgA Nephropathy (IgAN)

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

Study Overview

• Status: Recruiting
• Conditions: IgA Nephropathy; Berger Disease
• Intervention / Treatment: Biological: Atacicept; Other: Placebo to match Atacicept

Detailed Description

This is a multi-part study comprising of the original Phase 2b study (active, no longer recruiting) and the addition of a separate pivotal Phase 3 study (active, recruiting).

After the completion of the primary results for the Ph 2b dose ranging study, the pivotal study (active, recruiting) 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.

• Study Type: Interventional
• Enrollment (Estimated): 376
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Vera Therapeutics, Inc. Clinical Trials Information; Phone Number: 650-770-0077; Email: clinicaltrials@veratx.com

Study Locations

• United States
  • California
    • Brisbane, California, United States, 94005
      • Recruiting
      • ORIGIN 3 Global Site Contact Information
      • Contact: Brisbane, California; Phone Number: 650-770-0077; Email: clinicaltrials@veratx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atacicept Dose 150mg; Atacicept 150mg once weekly subcutaneous (SC) injections	Biological: Atacicept; Once weekly subcutaneous (SC) injections by prefilled syringe; Other Names: VT-001
Placebo Comparator: Placebo to match Atacicept (Part C/D); Placebo to match Atacicept once weekly subcutaneous (SC) injection	Other: Placebo to match Atacicept; Once weekly subcutaneous (SC) injections by prefilled syringe

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in urine protein to creatinine ratio (UPCR)	UPCR based on 24 hour urine collection	36 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized rate of change in estimated glomerular filtration rate (eGFR)	eGFR calculated by CKD-EPI formula	52 and 104 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in urine protein to creatinine ratio (UPCR)	UPCR based on 24 hour urine collection	12, 48, 96 Weeks and Week 26 follow up
Change from baseline in estimated glomerular filtration rage (eGFR)	eGFR calculated by CKD-EPI formula	12, 24, 36, 48, 96 Weeks and 26 Week follow up
Change from baseline in IgA, IgG, IgM, C3, C4 and Gd-IgA1 levels	Serum measurement of IgA, IgG, IgM, C3, C4 and Gd-IgA1	12, 24, 36, 48, 96 Weeks
Number of participants with adverse events during the double-blind treatment period	Safety and tolerability	Through 36 Weeks
Evaluate serum PK of atacicept	Serum concentration of atacicept	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Vera Therapeutics, Inc.
• Investigators: Study Director: Rubeen Israni, Sr. Director, Clinical Development

Publications and helpful links

Helpful Links

• Vera Therapeutics, Inc Company Website
• ORIGIN 3 Study Website

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2023
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: January 11, 2021
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Berger Disease; Berger's Disease; IGA Glomerulonephritis; IGA Nephropathy; Immunoglobulin A Nephropathy Nephritis; IGA Type Nephropathy, IGA; Iga Nephropathy 1
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis, IGA
• Other Study ID Numbers: VT-001-0050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No