Primary IgA NephropathyPhase 2NCT04014335
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
A Phase 2 study testing IONIS-FB-LRx in people with Primary IgA Nephropathy, run by Ionis Pharmaceuticals, Inc. at 7 sites in 4 countries.
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary IgA Nephropathy
- What is being tested?
- IONIS-FB-LRx
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 7 sitesin 4 countries
- Study dates
- 4 Dec 2019to 11 Apr 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
Australia3 sites
IONIS Investigative Site
Liverpool, New South Wales, 2170
IONIS Investigative Site
Parkville, Victoria, 3050
IONIS Investigative Site
St Leonards, New South Wales, 2065
Canada2 sites
IONIS Investigative Site
Toronto, Ontario, M4G 3E8
IONIS Investigative Site
Vancouver, British Columbia, V6Z 1Y6
About this study
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
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.
Read the 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.
- Conditions
- Primary IgA Nephropathy
- Being tested
- IONIS-FB-LRx
- Medical subject headings
- Glomerulonephritis, IGA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IONIS-FB-LRxDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| IONIS-FB-LRx | Experimental | Not described Receives: Drug: IONIS-FB-LRx |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Reduction in 24-hour Urine Protein Excretion
Measured: 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
Measured: 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)
Measured: Baseline to Week 29
Absolute Reduction in Proteinuria (UPCr Ratio)
Measured: Baseline to Week 29
Percent Change from Baseline in Plasma Factor B (FB)
Measured: Up to Week 29
Percent Change from Baseline in Plasma AH50
Measured: Up to Week 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2019
- Study start4 Dec 2019
- Primary completion8 Feb 2024
- Study completion11 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Primary IgA NephropathyStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04014335
- Sponsor's protocol ID
- ISIS 696844-CS4
- Status last verified
- Jan 2025
- First submitted
- 8 Jul 2019
- Last updated
- 23 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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. 2026 Mar;109(3):592-601. doi: 10.1016/j.kint.2025.11.017. Epub 2025 Dec 22.
PubMed 41443406Tekendo-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.
PubMed 39331470
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04014335
- Acronym / sponsor ID
- ISIS 696844-CS4
- Conditions
- Primary IgA Nephropathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 4 Dec 2019 (actual)
- Primary completion
- 8 Feb 2024 (actual)
- Study completion
- 11 Apr 2024 (actual)
- First posted
- 10 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IONIS-FB-LRx | Experimental | Drug: IONIS-FB-LRx |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IONIS-FB-LRxParticipants 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. | Drug | IONIS-FB-LRx |
Primary outcome
Percent Reduction in 24-hour Urine Protein Excretion
Time frame: 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)
5 secondary outcomes
Absolute Reduction in 24-hour Urine Protein Excretion
Time frame: 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)
Time frame: Baseline to Week 29
Absolute Reduction in Proteinuria (UPCr Ratio)
Time frame: Baseline to Week 29
Percent Change from Baseline in Plasma Factor B (FB)
Time frame: Up to Week 29
Percent Change from Baseline in Plasma AH50
Time frame: Up to Week 29
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2025.
- Derived from this study: PubMed 41443406Barbour 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. 2026 Mar;109(3):592-601. doi: 10.1016/j.kint.2025.11.017. Epub 2025 Dec 22.
- Derived from this study: PubMed 39331470Tekendo-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IONIS-FB-LRx in people with Primary IgA Nephropathy, run by Ionis Pharmaceuticals, Inc. at 7 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Australia, Canada, New Zealand, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Reduction in 24-hour Urine Protein Excretion (time frame: 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04014335, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2025.