Lupus Nephritis
Conditions
Keywords
lupus nephritis, calcineurin inhibitors, voclosporin
Brief summary
An exploratory study assessing the ability of biomarkers measured at 8 weeks to predict clinical response over 24 and 48 weeks in subjects taking voclosporin 23.7 mg twice daily (BID) in combination with standard of care in patients with active lupus nephritis
Detailed description
Voclosporin is a novel calcineurin inhibitor (CNI) intended for use in the prevention of organ graft rejection and for the treatment of autoimmune diseases. The aim of the current development program is to investigate whether voclosporin added to the standard of care treatment in active Lupus Nephritis (LN) is able to reduce disease activity, as measured by a reduction in proteinuria. The background therapy will be mycophenolate mofetil (MMF) 2 g daily, initial treatment with IV methylprednisolone followed by a reducing course of oral corticosteroids. Patients with active, flaring LN will be eligible to enter the study. They are required to have a diagnosis of LN according to established diagnostic criteria (American College of Rheumatology) and clinical and biopsy features suggestive of active nephritis. Efficacy will be assessed by the ability of the drug combination to reduce the level of proteinuria while demonstrating an acceptable safety profile.
Interventions
DRUGvoclosporin
Sponsors
Aurinia 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
Key Inclusion Criteria: * Diagnosis of systemic lupus erythematosus (SLE) according to the American College of Rheumatology criteria (1997; see Appendix 6). * Kidney biopsy within 24 months prior to screening with a histologic diagnosis of lupus nephritis International Society of Nephrology/Renal Pathology Society Classes III, IV-S or IV-G, (A) or (A/C); or Class V, alone or in combination with Class III or IV. * Laboratory evidence of active nephritis at screening, defined as: Class III, IV-S or Class IV-G (proteinuria ≥1000 mg/24 hours when assessed by 24 hour urine collection, defined by a urine protein/creatinine ratio (UPCR) of ≥1.0 mg/mg assessed in a first morning void urine specimen). Class V, alone or in combination with Class III or IV, (proteinuria ≥1,500 mg/24 hours when assessed by 24 hour urine collection, defined by a UPCR of ≥1.5 mg/mg assessed in a first morning void urine specimen). Key
Exclusion criteria
* Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation of ≤45 mL/min/1.73 m2 at screening * Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period. * A previous kidney transplant or planned transplant within study treatment period. * Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Subjects with cervical dysplasia that is cervical intraepithelial neoplasia 1, but have been treated with conization or loop electrosurgical excision procedure, and have had a normal repeat Papanicolaou smear test (PAP) are allowed. * Lymphoproliferative disease or previous total lymphoid irradiation. * Severe viral infection (such as Cytomegalovirus (CMV), Hepatitis B virus (HBV), Hepatitis C virus (HCV)) within 3 months of screening; or known human immunodeficiency virus infection. * Active tuberculosis (TB), or known history of TB/evidence of old TB if not taking prophylaxis with isoniazid. * Other known clinically significant active medical conditions, such as: * Severe cardiovascular disease including congestive heart failure, history of cardiac dysrhythmia or congenital long QT syndrome. QT interval duration corrected for heart rate using method of Fridericia (QTcF) exceeding 480 msec in the presence of a normal QRS interval (\<110 msec) at time of screening will result in exclusion. * Liver dysfunction (aspartate aminotransferase, alanine aminotransferase, or bilirubin greater than 2.5 times the upper limit of normal) at screening and confirmed before enrollment. * Chronic obstructive pulmonary disease or asthma requiring oral steroids. * Bone marrow insufficiency unrelated to active systemic lupus erythematosus (SLE) (according to Investigator judgment) with white blood cell count \<2,500/mm3; absolute neutrophil count \<1.3 × 103/μL; thrombocytopenia (platelet count \<50,000/mm3). * Active bleeding disorders. * Current infection requiring IV antibiotics.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Reduction or Normalization of Urine Protein/Creatinine Ratio (UPCR) | 24 weeks |
| Number of Participants With Reduction or Normalization of Anti ds DNA | 24 weeks |
| Number of Participants With Reduction or Normalization of C3 | 24 weeks |
| Number of Participants With Reduction or Normalization of C4 | 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Remission at Week 24 | week 24 | * Confirmed Protein/creatinine ratio of ≤0.5 mg/mg and * eGFR ≥ 60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of ≥20% |
| Number of Participants With Complete Remission at Week 48 | week 48 | * Confirmed Protein/creatinine ratio of ≤0.5 mg/mg and * eGFR ≥ 60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of ≥20% Safety Population - 2 subjects failed to provide sufficient data to ascertain week 48 response |
Countries
Malaysia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Voclosporin 23.7 mg Twice Daily (BID) in Combination With Standard of Care Voclosporin 23.7 mg Twice Daily (BID) | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Voclosporin 23.7 mg Twice Daily (BID) in Combination With Standard of Care |
|---|---|
| Age, Continuous | 28.7 years STANDARD_DEVIATION 5.14 |
| Duration of systemic lupus erythematosus, proteinuria and lupus nephritis Duration of Lupus Nephritis (LN) | 5.8 years STANDARD_DEVIATION 3.49 |
| Duration of systemic lupus erythematosus, proteinuria and lupus nephritis Duration of proteinuria | 5.9 years STANDARD_DEVIATION 3.38 |
| Duration of systemic lupus erythematosus, proteinuria and lupus nephritis Duration of systemic lupus erythematosus (SLE) | 7.3 years STANDARD_DEVIATION 3.23 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Malaysia | 10 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 3 / 10 |
Outcome results
Primary
Number of Participants With Reduction or Normalization of Anti ds DNA
Time frame: 24 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Voclosporin 23.7 mg Twice Daily (BID) in Combination With Standard of Care | Number of Participants With Reduction or Normalization of Anti ds DNA | 4 Participants |
Primary
Number of Participants With Reduction or Normalization of C3
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Voclosporin 23.7 mg Twice Daily (BID) in Combination With Standard of Care | Number of Participants With Reduction or Normalization of C3 | 2 Participants |
Primary
Number of Participants With Reduction or Normalization of C4
Time frame: 24 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Voclosporin 23.7 mg Twice Daily (BID) in Combination With Standard of Care | Number of Participants With Reduction or Normalization of C4 | 2 Participants |
Primary
Number of Participants With Reduction or Normalization of Urine Protein/Creatinine Ratio (UPCR)
Time frame: 24 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Voclosporin 23.7 mg Twice Daily (BID) in Combination With Standard of Care | Number of Participants With Reduction or Normalization of Urine Protein/Creatinine Ratio (UPCR) | 7 Participants |
Secondary
Number of Participants With Complete Remission at Week 24
* Confirmed Protein/creatinine ratio of ≤0.5 mg/mg and * eGFR ≥ 60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of ≥20%
Time frame: week 24
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Voclosporin 23.7 mg Twice Daily (BID) in Combination With Standard of Care | Number of Participants With Complete Remission at Week 24 | 7 Participants |
95% CI: [34.8, 93.3]
Secondary
Number of Participants With Complete Remission at Week 48
* Confirmed Protein/creatinine ratio of ≤0.5 mg/mg and * eGFR ≥ 60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of ≥20% Safety Population - 2 subjects failed to provide sufficient data to ascertain week 48 response
Time frame: week 48
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Voclosporin 23.7 mg Twice Daily (BID) in Combination With Standard of Care | Number of Participants With Complete Remission at Week 48 | 4 Participants |
95% CI: [15.7, 84.3]