A Randomized, Controlled Double-blind Study Comparing the Efficacy and Safety of Orelvo (voclosporin) (23.7 mg Twice Daily) with Placebo in Achieving Renal Response in Subjects with Active Lupus Nephritis - AURORA (AURinia Orelvo Renal Assessments) 1: Aurinia Renal Response in Active Lupus with Voclosporin

• Register: EUCTR
• Last refreshed on: 21 December 2021
• Main ID: EUCTR2016-004045-81-BG
• Date of registration: 06/03/2017
• Prospective Registration: Yes
• Primary sponsor: Aurinia Pharmaceuticals, Inc.
• Public title: A Randomized, Controlled Double-blind Study Comparing the Efficacy and Safety of Orelvo (voclosporin) (23.7 mg Twice Daily) with Placebo in Achieving Renal Response in Subjects with Active Lupus Nephritis - AURORA (AURinia Orelvo Renal Assessments) 1: Aurinia Renal Response in Active Lupus with Voclosporin
• Scientific title: A Randomized, Controlled Double-blind Study Comparing the Efficacy and Safety of Orelvo (voclosporin) (23.7 mg Twice Daily) with Placebo in Achieving Renal Response in Subjects with Active Lupus Nephritis - AURORA (AURinia Orelvo Renal Assessments) 1: Aurinia Renal Response in Active Lupus with Voclosporin
• Date of first enrolment: 16/05/2017
• Target sample size: 324
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004045-81
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belarus, Brazil, Bulgaria, Canada, Chile, Colombia, Costa Rica, Croatia, Dominican Republic, Guatemala, Japan, Korea, Republic of, Macedonia, the former Yugoslav Republic of, Malaysia, Mexico, Netherlands, Peru, Philippines, Poland, Russian Federation, Serbia, South Africa, Spain, Taiwan, Thailand, Turkey, Ukraine, United States, Vietnam

Contacts

• Name: Project Management
• Affiliation: Worldwide Clinical Trials Ltd

• Name: Project Management
• Affiliation: Worldwide Clinical Trials Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
• Written informed consent before any study specific procedures are performed.
• Male or female subjects with a minimum age of 18 (or legal age of consent if >18 years) to 75 years of age, inclusive, at the time of screening (Visit 1).
• Previous diagnosis of SLE according to the American College of Rheumatology criteria
• Subjects with evidence of active nephritis, defined as follows:
- Kidney biopsy result within 2 years prior to screening indicating Class III, IV S, IV-G (alone or in combination with Class V), or Class V LN (see Appendix 3) with a doubling or greater increase of urine protein creatinine ratio (UPCR) within the last 6 months to a minimum of =1.5 mg/mg for Class III/IV or to a minimum of =2 mg/mg for Class V at screening. Biopsy results over 6 months prior to screening must be reviewed with a medical monitor to confirm eligibility.
OR
- Kidney biopsy result within 6 months prior to screening indicating Class III, IV S or IV-G (alone or in combination with Class V) LN with a UPCR of =1.5 mg/mg at screening.
OR
- Kidney biopsy result within 6 months prior to screening indicating Class V LN and a UPCR of =2 mg/mg at screening.
A biopsy can be performed during screening, if not available. The above criteria must be fulfilled at baseline.
• In the opinion of the Investigator, subject requires high-dose corticosteroids and immunosuppressive therapy.
• Subject is willing to take oral MMF for the duration of the study, either by continuing current MMF therapy or by initiating it on or before the Baseline Visit.
• Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline. Two effective forms of contraception must be used simultaneously unless abstinence is the chosen method. Subjects must use effective contraception during the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 310
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion criteria:
• Subjects unable or unwilling to give written informed consent and/or to comply with study procedures.
• Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation of =45 mL/minute/1.73 m2 at screening confirmed before randomization.
• Currently taking or known need for any of the medications listed in protocol Section 7.8, Prohibited Therapy and Concomitant Treatment at screening or during the study. This includes prohibited medications prior to screening as specified in protocol Section 7.8.1, Prohibited Medications.
• 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.
• Any known hypersensitivity or contraindication to MMF, mycophenolic acid, cyclosporine, corticosteroids or any components of these drug products.
• Current or medical history of:
- Congenital or acquired immunodeficiency.
- In the opinion of the Investigator, clinically significant drug or alcohol abuse within 2 years prior to screening.
- 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 test are allowed.
- Lymphoproliferative disease or previous total lymphoid irradiation.
- Severe viral infection (e.g., cytomegalovirus, hepatitis B virus, hepatitis C virus) within 3 months of screening; or known HIV infection. Severe viral infection is defined as active disease requiring antiviral therapy.
- Active tuberculosis (TB), or known history of TB/evidence of old TB if not taking prophylaxis with isoniazid (see protocol Section 9.2.1, Screening Visit Procedures).
• 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 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 =2.5 times the upper limit of normal) at screening and, if abnormal at screening, then confirmed that the levels have returned to <2.5 times upper limit of normal before randomization.
- Chronic obstructive pulmonary disease or asthma requiring oral steroids.
- Bone marrow insufficiency unrelated to active SLE (according to Investigator judgment) with white blood cell count <2,500/mm3; absolute neutrophil count <1.3 × 10(3)/µL; thrombocytopenia (platelet count <50,000/mm3).
- Active bleeding disorders.
- Current infection requiring IV antibiotics.
• Any overlapping autoimmune condition for which the condition or the treatment of the condition may affect the study assessments or outcomes (e.g., scleroderma with significant pulmonary hypertension; any condition for which additional immunosuppression is indicated). Overlapping conditions for which the condition or treatment is not expected to affect assessments or outcomes (e.g., Sjögren’s syndrome) are not excluded.
• No vaccines using live organisms, virus or bacterial,

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Lupus Nephritis
MedDRA version: 20.1 Level: PT Classification code 10025140 Term: Lupus nephritis System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Orelvo
Product Code: Voclosporin
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Voclosporin
CAS Number: 515814-01-4
Current Sponsor code: ISA247
Other descriptive name: Orelvo
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 7.9-
Pharmaceutical form of the placebo: Capsule, soft
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Renal response at Week 52 will be adjudicated by the Clinical Endpoints Committee based on the following parameters:
• UPCR of =0.5 mg/mg, and
• eGFR =60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of >20%, and
• Received no rescue medication for LN (see protocol Section 7.8, Prohibited Therapy and Concomitant Treatment), and
• Did not receive more than 10 mg prednisone for =3 consecutive days or for =7 days in total during Weeks 44 through 52, just prior to the renal response assessment.
Subjects who withdraw from the study prior to the Week 52 assessment will be defined as non responders.

Main Objective: To assess the efficacy of Orelvo (voclosporin) compared with placebo in achieving renal response after 52 weeks of therapy in subjects with active lupus nephritis (LN)

Timepoint(s) of evaluation of this end point: week 52

Secondary Objective: To assess the safety and tolerability of Orelvo over 52 weeks compared with placebo in subjects with active LN

Secondary Outcome(s)

Secondary end point(s): • Time to UPCR of =0.5 mg/mg
• Partial renal response as defined by 50% reduction from baseline in UPCR at Weeks 24 and 52
• Time to 50% reduction in UPCR from baseline
• Renal response at Week 52 (based on definition of primary endpoint)
• Duration of UPCR <0.5 mg/mg
• Proportion of subjects experiencing a confirmed >30% decrease from
baseline in eGFR at each timepoint.
•Change from baseline in UPCR at each time point.
•Change from baseline in serum creatinine, urine protein, and eGFR.
•Change from screening in immunology parameters (complement 3 (C3), C4, and anti double-stranded DNA).
•Renal response with low-dose steroids (defined as renal response in the presence of corticosteroids of =2.5 mg between Weeks 16 to 24 and Weeks 44 to 52).
•Change from baseline in health-related quality of life at Weeks 12, 24, and 52.
•Health Resource Utilization at Weeks 24 and 52.
•Change from baseline in the Safety of Estrogens in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity (SELENA-SLEDAI) Index score at Weeks 24 and 52.

Timepoint(s) of evaluation of this end point: week 24 and 52

Secondary ID(s)

AUR-VCS-2016-01

NCT03021499

Source(s) of Monetary Support

Aurinia Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 16/05/2017
Contact:

Results

• Results available: Yes
• Date Posted: 12/05/2021
• Date Completed: 10/10/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-004045-81/results