Clinical study comparing the efficacy in the achievement of the remission (measured as reduction of proteinuria) and safety of two different doses of voclosporin and non active drug (placebo) in patients suffering from active lupus nephritis

• Register: EUCTR
• Last refreshed on: 3 October 2016
• Main ID: EUCTR2012-003364-51-ES
• Date of registration: 07/07/2014
• Prospective Registration: Yes
• Primary sponsor: Aurinia Pharmaceuticals Inc.
• Public title: Clinical study comparing the efficacy in the achievement of the remission (measured as reduction of proteinuria) and safety of two different doses of voclosporin and non active drug (placebo) in patients suffering from active lupus nephritis
• Scientific title: A Randomized, Controlled Double-blind Study Comparing the Efficacy and Safety of Voclosporin (23.7 mg BID, or 39.5 mg BID) with Placebo in Achieving Remission in Patients with Active Lupus Nephritis - AURA-LV: Aurinia Urinary protein Reduction Active ? Lupus with Voclosporin
• Date of first enrolment: 24/10/2014
• Target sample size: 222
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003364-51
• 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: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belarus, Bulgaria, Georgia, Guatemala, Mexico, Poland, Russian Federation, Serbia, Spain, Sri Lanka, Ukraine, United States

Contacts

• Name: Regulatory Deparment
• Affiliation: Pharm-Olam International (Spain) S.L.U.

• Name: Regulatory Deparment
• Affiliation: Pharm-Olam International (Spain) S.L.U.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent (by subject or legally acceptable representative) before any study-specific procedures are performed.
2. Male or female subjects aged 18 to 75 years inclusive at the time of consent.
3. Diagnosis of systemic lupus erythematosus (SLE) according to the American College of Rheumatology criteria (1997; see Appendix 7).
4. Kidney biopsy within 6 months prior to screening (Visit 1) 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; see Appendix 5.
5. Laboratory evidence of active nephritis at screening, defined as:
? Class III
Confirmed proteinuria ?2,000 mg/24 hours when assessed by 24 hour urine
collection, defined by a urine protein/creatinine ratio (UPCR) of ?2 mg/mg
assessed in a first morning void urine specimen (2 samples).
? Class IV-S or Class IV-G
Confirmed 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 (2 samples).
? Class V (alone or in combination with Class III or IV)
Confirmed proteinuria ?2,000 mg/24 hours when assessed by 24 hour urine
collection, defined by a UPCR of ?2 mg/mg assessed in a first morning
void urine specimen (2 samples).
6. In the opinion of the Investigator, subject requires high dose corticosteroids and immunosuppressive therapy.
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 222
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
1. Subjects unable or unwilling to give written informed consent and/or to comply with study procedures.
2. Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation of ?45 mL/min/1.73 m2 at screening (Visit 1)
3. Currently taking or known need for any of the medications listed in Section 7.8, Prohibited Therapy and Concomitant Treatment, page 58.
4. Serum potassium >5.5 mmol/L at screening confirmed before randomization.
5. Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period.
6. A previous kidney transplant or planned transplant within study treatment period.
7. In the opinion of the Investigator, subject does not require long-term immunosuppressive treatment (in addition to corticosteroids).
8. Any known hypersensitivity or contraindication to MMF, mycophenolic acid, cyclosporine, corticosteroids or any components of these drug products.
9. Current or medical history of:
? Pancreatitis or gastrointestinal hemorrhage within 6 months prior to screening.
? Active unhealed peptic ulcer within 3 months prior to screening. If an ulcer has healed and the subject is on adequate therapy, the subject may be randomized.
? Congenital or acquired immunodeficiency.
? In the opinion of the Investigator, clinically significant drug or alcohol abuse 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 PAP are allowed.
? Lymphoproliferative disease or previous total lymphoid irradiation.
? Severe viral infection (such as CMV, HBV, 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.
10. 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. QTcF (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 greater than 2.5 times the upper limit of normal) at screening and confirmed 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 × 103/?L; thrombocytopenia (platelet count <50,000/mm3).
? Active bleeding disorders.
? Current infection requiring IV antibiotics.
11. 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., Sjogren?s syndrome) are not excluded.
12. Other major physical or psychiatric i

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

Health Condition(s) or Problem(s) studied

Active lupus nephritis
MedDRA version: 17.0 Level: PT Classification code 10025140 Term: Lupus nephritis System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Product Name: Voclosporin
Product Code: ISA247
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Voclosporin
CAS Number: 515814-01-4
Current Sponsor code: ISA247
Other descriptive name: VOCLOSPORINA
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

Trade Name: Mycophenolate Mofetil (MMF)
Product Name: Mycophenolate Mofetil
Product Code: MMF
Pharmaceutical Form: Tablet
INN or Proposed INN: MYCOPHENOLATE MOFETIL
CAS Number: 128794-94-5
Current Sponsor code: MMF
Other descriptive name: MYCOPHENOLATE MOFETIL
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 24

Primary end point(s): The number of subjects achieving complete remission at 24 weeks. Complete remission is defined as: Complete remission as defined as:
? Confirmed protein/creatinine ratio of ?0.5 mg/mg, and
? No confirmed decrease from baseline in eGFR of ?20%.
Subjects who receive rescue medication for lupus (refer to Section 7.8, Prohibited Therapy and Concomitant Treatment, page 58) or ?10 mg prednisone after Week 16 will not be considered as achieving complete remission.

Main Objective: ? To assess the efficacy of 2 doses of voclosporin compared to placebo in achieving complete remission after 24 weeks of therapy in subjects with active Lupus Nephritis (LN).

Secondary Objective: ? To assess the safety and tolerability of 2 doses of voclosporin over 48 weeks
compared to placebo in subjects with active LN.

? To assess the efficacy of 2 doses of voclosporin versus placebo over 48 weeks in
subjects with active LN.

Secondary Outcome(s)

Secondary end point(s): ? Complete remission as per the primary endpoint analyzed at Week 48.
? Complete remission in the presence of low dose steroids at Week 24 (defined as confirmed complete remission and ?5 mg prednisone for ?8 weeks) and Week 48 (defined as confirmed complete remission and ?5 mg prednisone for ?12 weeks).
? Time to complete remission.
? Time to (and proportion achieving) early, sustained complete remission (defined as complete remission which occurs on or before Week 24 which is sustained through Week 48).
? Time to sustained complete remission (defined as the first occurrence of complete remission which is sustained through Week 48).
? Duration of complete remission (in months).
? Partial remission as defined by 50% reduction in protein/creatinine ratio from
baseline at Weeks 24 and 48.
? Time to partial remission.
? Time to (and proportion achieving) early, sustained partial remission (partial
remission which occurs on or before Week 24 which is sustained through
Week 48).
? Time to sustained partial remission (defined as the first occurrence of partial
remission which is sustained through Week 48).
? Change from baseline in UPCR at Weeks 24 and 48.
? Change from baseline in the Safety of Exogenous Estrogens in Lupus
Erythematosus National Assessment - Systemic Lupus Erythematosus Disease
Activity Index score at Weeks 24 and 48.
? Change from baseline in serum creatinine, urine protein, serum albumin, eGFR
at each visit measured.
? Proportion of subjects with active urinary sediment (defined by >10 red blood
cells (RBC) per high powered field with dysmorphic RBC and/or RBC casts on
urinalysis of a urine sample which has a minimum volume of 50 mL) at each
visit measured.
? Change from baseline in immunology parameters (C3, C4, and anti-double-stranded DNA) and biomarkers at each visit measured

Timepoint(s) of evaluation of this end point: Timepoints as specified in section E.5.1.1

Secondary ID(s)

AUR-VCS-2012-01

114577

Source(s) of Monetary Support

Aurinia Pharmaceuticals Inc.