A Study to Evaluate the Effectiveness and Safety of IONIS-FB-LRx, an Antisense Inhibitor of Complement Factor B, in Adult Participants With Primary IgA Nephropathy

An Open-Label Phase 2a Clinical Study to Evaluate the Effectiveness and Safety of IONIS-FB-LRx, an Antisense Inhibitor of Complement Factor B, in Adult Subjects With Primary IgA Nephropathy

The purpose of this study is to evaluate the effectiveness and safety of IONIS-FB-LRx, an antisense inhibitor of complement factor B messenger ribonucleic acid (CFB mRNA), and to evaluate the effect of IONIS-FB-LRx on plasma factor B (FB) levels and serum AH50, CH50 activity in participants with primary immunoglobulin A (IgA) nephropathy.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary IgA Nephropathy
• Intervention / Treatment: Drug: IONIS-FB-LRx

Detailed Description

This is a Phase 2, single arm open-label clinical study in up to 25 participants that will consist of a screening period, a 24-week treatment period, an optional treatment extension period of up to an additional 48 weeks, and a 12- week post-treatment follow-up evaluation period.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ionis Pharmaceuticals; Phone Number: (844) 727-6672; Email: ionisNCT04014335study@clinicaltrialmedia.com

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Ionis Investigative Site
    • St Leonards, New South Wales, Australia, 2065
      • Ionis Investigative Site
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Ionis Investigative Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Ionis Investigative Site
  • Ontario
    • Toronto, Ontario, Canada, M4G 3E8
      • Ionis Investigative Site
• New Zealand
  • Christchurch, New Zealand, 8011
    • Ionis Investigative Site
• Singapore
  • Singapore, Singapore, 168582
    • Ionis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal OR use a highly effective method of birth control
• Biopsy-proven primary immunoglobulin A (IgA) nephropathy
• Hematuria
• Proteinuria

Exclusion Criteria

• Clinically significant abnormalities in medical history (e.g., dementia, stroke, acute coronary syndrome, thrombocytopenia, or major surgery within 3 months of Screening)
• Diagnosis of primary or secondary immunodeficiencies of B-lymphocyte function, splenectomy, or history of recurrent meningococcal disease
• Active infection 30 days prior to study
• Estimated glomerular filtration rate (eGFR) ≤ 40 milliliters per minute per 1.73 square meters (mL/min/1.73m^2) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
• Presence of another renal disease including, but not limited to, diabetes and/or diabetic nephropathy, thin basement membrane disease, Alport's disease, IgA Nephritis (Henoch-Schonlein purpura), lupus nephritis, Minimal Change Disease, post-infectious glomerulonephritis or any other cause of proteinuria or secondary IgA nephropathy (including, but not limited to Celiac disease, Crohn's disease, human immunodeficiency virus (HIV), liver cirrhosis)
• History of renal transplant or another organ transplant
• Treatment with another investigational drug, biological agent, or device within 6 months of screening, or 5 half-lives of investigational agent, whichever is longer
• Administration of immunosuppressive/immunomodulatory medication 12 months prior to study drug administration, except for short-term treatments.
• Other protocol-specified inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IONIS-FB-LRx	Drug: IONIS-FB-LRx; Participants will receive IONIS-FB-LRx, by subcutaneous injection (SC) at Week 1 and every 4 weeks through Week 25. Optional 48-week Extension, with drug dosing continuing every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Reduction in 24-hour Urine Protein Excretion	Baseline to Week 29 (If participant discontinues Study Drug prior to Week 25, Baseline and 4 weeks after the last dose of Study Drug will be measured)

Secondary Outcome Measures

Outcome Measure	Time Frame
Absolute Reduction in 24-hour Urine Protein Excretion	Baseline to Week 29 (If participant discontinues Study Drug prior to Week 25, Baseline and 4 weeks after the last dose of Study Drug will be measured)
Absolute Reduction in Albuminuria (UACr Ratio)	Baseline to Week 29
Absolute Reduction in Proteinuria (UPCr Ratio)	Baseline to Week 29
Percent Change from Baseline in Plasma Factor B (FB)	Up to Week 29
Percent Change from Baseline in Plasma AH50	Up to Week 29

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2019
• Primary Completion (Actual): February 8, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (Actual): July 10, 2019

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 6, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• 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: ISIS 696844-CS4

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