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

NCT04014335 | Completed Phase 2 FDA Drug

• 1 other identifier: ISIS 696844-CS4
• Study Type: interventional
• Target: 23
• Locations: 4 countries
• Sites: 7

Brief Summary

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.

Conditions

Primary IgA Nephropathy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (1)

IONIS-FB-LRx

EXPERIMENTAL

Drug: IONIS-FB-LRx

Interventions

IONIS-FB-LRx DRUG

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.

IONIS-FB-LRx

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (7)

IONIS Investigative Site

Liverpool, New South Wales, 2170, Australia

Location

IONIS Investigative Site

St Leonards, New South Wales, 2065, Australia

Location

IONIS Investigative Site

Parkville, Victoria, 3050, Australia

Location

IONIS Investigative Site

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

IONIS Investigative Site

Toronto, Ontario, M4G 3E8, Canada

Location

IONIS Investigative Site

Christchurch, 8011, New Zealand

Location

IONIS Investigative Site

Singapore, 168582, Singapore

Location

Related Publications (2)

• Barbour SJ, Hladunewich MA, McCaleb ML, Robson R, Barrett TD, Yin L, Frazer-Abel A, Garg JP, Geary R, Schneider E, Brice GT. A single-arm phase 2 trial of an investigational RNA therapeutic to complement factor B sefaxersen for treatment of IgA nephropathy. Kidney Int. 2025 Dec 22:S0085-2538(25)01007-5. doi: 10.1016/j.kint.2025.11.017. Online ahead of print.

  PMID: 41443406 DERIVED

• Tekendo-Ngongang C, Gleeson JG, Mignon L. Treating the Untreatable: Antisense Oligonucleotides as an Individualized Therapy for Rare Genetic Kidney Diseases. J Am Soc Nephrol. 2024 Dec 1;35(12):1774-1777. doi: 10.1681/ASN.0000000532. Epub 2024 Sep 27. No abstract available.

  PMID: 39331470 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, IGA

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: July 10, 2019
• Study Start: December 4, 2019
• Primary Completion: February 8, 2024
• Study Completion: April 11, 2024
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); NZ (1); SG (1); CA (2)