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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 Purpose

Primary IgA Nephropathy

Status

Active

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

IONIS-FB-LRx

About this trial

This is an interventional treatment trial for Primary IgA Nephropathy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

IONIS Investigative Site
IONIS Investigative Site
IONIS Investigative Site
IONIS Investigative Site
IONIS Investigative Site
IONIS Investigative Site
IONIS Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IONIS-FB-LRx

Arm Description

Outcomes

Primary Outcome Measures

Percent Reduction in 24-hour Urine Protein Excretion

Secondary Outcome Measures

Absolute Reduction in 24-hour Urine Protein Excretion

Absolute Reduction in Albuminuria (UACr Ratio)

Absolute Reduction in Proteinuria (UPCr Ratio)

Percent Change from Baseline in Plasma Factor B (FB)

Percent Change from Baseline in Plasma AH50

Full Information

NCT ID

NCT04014335

First Posted

July 8, 2019

Last Updated

July 28, 2023

Sponsor

Ionis Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04014335

Brief Title

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

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 4, 2019 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ionis Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary IgA Nephropathy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

IONIS-FB-LRx

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

IONIS-FB-LRx

Intervention Description

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.

Primary Outcome Measure Information:

Title

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)

Secondary Outcome Measure Information:

Title

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)

Title

Absolute Reduction in Albuminuria (UACr Ratio)

Time Frame

Baseline to Week 29

Title

Absolute Reduction in Proteinuria (UPCr Ratio)

Time Frame

Baseline to Week 29

Title

Percent Change from Baseline in Plasma Factor B (FB)

Time Frame

Up to Week 29

Title

Percent Change from Baseline in Plasma AH50

Time Frame

Up to Week 29

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Facility Information:

Facility Name

IONIS Investigative Site

City

Liverpool

State/Province

New South Wales

ZIP/Postal Code

2170

Country

Australia

Facility Name

IONIS Investigative Site

City

St Leonards

State/Province

New South Wales

ZIP/Postal Code

2065

Country

Australia

Facility Name

IONIS Investigative Site

City

Parkville

State/Province

Victoria

ZIP/Postal Code

3050

Country

Australia

Facility Name

IONIS Investigative Site

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V6Z 1Y6

Country

Canada

Facility Name

IONIS Investigative Site

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M4G 3E8

Country

Canada

Facility Name

IONIS Investigative Site

City

Christchurch

ZIP/Postal Code

8011

Country

New Zealand

Facility Name

IONIS Investigative Site

City

Singapore

ZIP/Postal Code

168582

Country

Singapore

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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