AURA-LV: Aurinia Urinary Protein Reduction Active - Lupus With Voclosporin (AURA-LV)
Ключові слова
Анотація
Опис
Voclosporin is a next generation CNI intended for use in the prevention of organ graft rejection and for the treatment of autoimmune diseases. The aim of the current study is to investigate whether voclosporin added to the standard of care treatment in active LN is able to reduce disease activity, as measured by a reduction in proteinuria. Two doses of voclosporin will be studied and compared in a placebo controlled trial on a background of MMF and 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.
Дати
| Востаннє перевірено: | 02/28/2017 |
| Перший поданий: | 05/13/2014 |
| Орієнтовна реєстрація подана: | 05/14/2014 |
| Опубліковано вперше: | 05/18/2014 |
| Останнє оновлення надіслано: | 09/20/2017 |
| Останнє оновлення опубліковано: | 09/24/2017 |
| Фактична дата початку навчання: | 05/31/2014 |
| Розрахункова дата первинного завершення: | 06/30/2016 |
| Розрахункова дата завершення дослідження: | 12/31/2016 |
Стан або захворювання
Втручання / лікування
Drug: Voclosporin High Dose
Drug: Voclosporin Low Dose
Drug: Placebo
Фаза
Групи рук
| Рука | Втручання / лікування |
|---|---|
| Experimental: Voclosporin Low Dose Voclosporin, oral, 23.7 mg BID | Drug: Voclosporin Low Dose |
| Experimental: Voclosporin High Dose Voclosporin, oral 23.7 mg BID until Week 2, then voclosporin, oral, 39.5 mg BID | Drug: Voclosporin High Dose |
| Placebo Comparator: Placebo Low dose: Voclosporin placebo, oral, 3 capsules BID
High dose: Voclosporin placebo, oral, 3 capsules BID until Week 2 then voclosporin placebo, oral, 5 capsules BID | Drug: Placebo |
Критерії прийнятності
| Вік, придатний для навчання | 18 Years До 18 Years |
| Стать, яка підходить для вивчення | All |
| Приймає здорових добровольців | Так |
| Критерії | Inclusion Criteria: Male or female subjects aged 18 to 75 years. Diagnosis of systemic lupus erythematosus (SLE) according to the American College of Rheumatology criteria. Kidney biopsy within 6 months prior to Screening (Visit 1) with a histologic diagnosis of lupus nephritis (International Society of Nephrology/Renal Pathology Society 2003 classification of lupus nephritis) 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 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). Exclusion Criteria: Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation of ≤45 mL/min/1.73 m2. 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. In the opinion of the Investigator, subject does not require long-term immunosuppressive treatment (in addition to corticosteroids). 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. - 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. 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. - 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 x 103/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. Overlapping conditions for which the condition or treatment is not expected to affect assessments or outcomes are not excluded. Subjects who are pregnant, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions. |
Результат
Заходи первинного результату
1. The number of subjects achieving complete remission at 24 Weeks [24 weeks]
Заходи вторинного результату
1. Complete remission as per the primary endpoint analyzed at Week 48 compared to placebo in subjects with active lupus nephritis. [Week 48]
2. Complete remission in the presence of low dose steroids at Week 24 and Week 48. [Weeks 24 and 48]
3. Time to (and proportion achieving) early, sustained complete remission [24 Weeks]
4. Time to sustained partial remission [48 Weeks]
5. Duration of complete remission (in months) [48 Weeks]
6. Complete remission at 48 weeks [48 Weeks]
7. Time to complete remission [48 weeks]
8. Partial remission [Weeks 24 and 48]
9. Time to partial remission [48 Weeks]
10. Time to (and proportion achieving) early, sustained partial remission [48 Weeks]
11. Time to sustained partial remission [48 Weeks]
12. Change from baseline in UPCR at Weeks 24 and 48. [Weeks 24 and 48]
13. Change from baseline in the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) - SLEDAI score at Weeks 24 and 48. [Weeks 24 and 48]
14. Change from baseline in serum creatinine, urine protein, serum albumin, eGFR at each visit measured. [50 Weeks]
15. Proportion of subjects with active urinary sediment at each visit measured. [50 Weeks]
16. Change from baseline in immunology parameters (C3, C4, and anti-double-stranded deoxyribonucleic acid (dsDNA) and biomarkers at each visit measured. [50 Weeks]
