Primary IgA Nephropathy
Conditions
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.
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.
Interventions
DRUGIONIS-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.
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| 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
| 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 |
Countries
Australia, Canada, New Zealand, Singapore
Outcome results
None listed