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

Primary IgA Nephropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04014335
• Other study ID #: ISIS 696844-CS4
• Status: Completed
• Phase: Phase 2
• Start date: December 4, 2019
• Est. completion date: April 11, 2024

Study information

• Verified date: May 2024
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: April 11, 2024
• Est. primary completion date: February 8, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• Kidney Diseases
• Primary IgA Nephropathy

Intervention

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.

Locations

Country	Name	City	State
Australia	IONIS Investigative Site	Liverpool	New South Wales
Australia	IONIS Investigative Site	Parkville	Victoria
Australia	IONIS Investigative Site	St Leonards	New South Wales
Canada	IONIS Investigative Site	Toronto	Ontario
Canada	IONIS Investigative Site	Vancouver	British Columbia
New Zealand	IONIS Investigative Site	Christchurch
Singapore	IONIS Investigative Site	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Australia,  Canada,  New Zealand,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	Absolute Reduction in Albuminuria (UACr Ratio)		Baseline to Week 29
Secondary	Absolute Reduction in Proteinuria (UPCr Ratio)		Baseline to Week 29
Secondary	Percent Change from Baseline in Plasma Factor B (FB)		Up to Week 29
Secondary	Percent Change from Baseline in Plasma AH50		Up to Week 29