Clinical trial NCT04014335: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary IgA Nephropathy
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-10
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent Reduction in 24-hour Urine Protein Excretion
timeFrame: 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:
measure: Absolute Reduction in 24-hour Urine Protein Excretion
timeFrame: 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)
measure: Absolute Reduction in Albuminuria (UACr Ratio)
timeFrame: Baseline to Week 29
measure: Absolute Reduction in Proteinuria (UPCr Ratio)
timeFrame: Baseline to Week 29
measure: Percent Change from Baseline in Plasma Factor B (FB)
timeFrame: Up to Week 29
measure: Percent Change from Baseline in Plasma AH50
timeFrame: Up to Week 29
Other outcomes:
Locations:
city: Liverpool
country: Australia
facility: IONIS Investigative Site
state: New South Wales
city: St Leonards
country: Australia
facility: IONIS Investigative Site
state: New South Wales
city: Parkville
country: Australia
facility: IONIS Investigative Site
state: Victoria
city: Vancouver
country: Canada
facility: IONIS Investigative Site
state: British Columbia
city: Toronto
country: Canada
facility: IONIS Investigative Site
state: Ontario
city: Christchurch
country: New Zealand
facility: IONIS Investigative Site
city: Singapore
country: Singapore
facility: IONIS Investigative Site
Study officials:
References: