A prospective, randomized, active controlled, parallel group, multi-center trial to assess the efficacy and safety of mycophenolate mofetil (MMF) in inducing response and maintaining remission in subjects with lupus nephritis. - Aspreva Lupus Management Study (ALMS)
- Conditions
- upus NephritisMedDRA version: 4.1Level: LowClassification code 10025140
- Registration Number
- EUCTR2004-004917-41-DE
- Lead Sponsor
- Aspreva International Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 358
1. Provision of written informed consent by subject or guardian, (with written assent for underage subjects)
2. Subject of either sex, 12 to 75 years of age (inclusive)
3. Diagnosis of SLE according to the American College of Rheumatology criteria (1997)
4. Kidney biopsy within the 6 months prior to first randomization with a histologic diagnosis of lupus nephritis (ISN/RPS 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. For biopsies reported according to ISDKC/WHO 1982 criteria, see Protocol Appendix 4
5. Laboratory evidence of active nephritis at screening, defined as:
Class IV-S or IV-G
•proteinuria =1000 mg/24 h or
•serum creatinine above 1.3 mg/dL (115 µmol/L) or
•active urinary sediment: any of >5 WBC/hpf, >5 RBC/hpf, 2+ or more on
dipstick, or red cell casts in the absence of infection or other causes
Class III or V
•proteinuria = 2000 mg/24 h or
•serum creatinine above 1.3 mg/dL (115 µmol/L)
Maintenance Phase:
1. Response after 24 weeks of induction therapy (Visit 9) or complete (renal) remission.
Response is defined as:
•Decrease in proteinuria, defined as decrease in the urine protein/creatinine ratio to <3 in subjects with baseline nephritic range proteinuria (>/=3 urine protein/creatinine ratio) or decrease in the urine protein/creatinine ratio by >/= 50% subjects with sub-nephrotic proteinuria (<3 urine protein/creatinine ratio). This ratio is based on the 24 hour urine collection.
•and stabilization of serum creatinine ( i.e. a week 24 serum creatinine level +/- 25% of baseline), or improvement.
Complete (renal) remission is definded as:
•return to normal serum creatinine, proteinuria •and an inactive urinary sediment.
Are the trial subjects under 18? yes
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Induction Phase:
1.Inability or unwillingness to provide written informed consent (and assent by underage subjects)
2. Inability or unwillingness to comply with the requirements of the protocol as determined by the investigator
3. In the opinion of the investigator, does not require long-term immunosuppressive treatment (in addition to corticosteroids)
4. Known hypersensitivity or contraindication to MMF, mycophenolic acid (MPA), cyclophosphamide, azathioprine (including known inherited TPMT deficiency), corticosteroids or any components of these drug products (e.g., allergy to Tween-80)
5. Pregnancy, nursing (breastfeeding) or use of a non-reliable method of contraception
6. Continuous dialysis starting more than 2 weeks before randomization into the induction phase and/or continuous dialysis with an anticipated duration of more than 8 weeks
7. Previous kidney transplant or planned transplant
8. Presence or history of:
•pancreatitis or GI hemorrhage within 6 months prior to first randomization
•active unhealed peptic ulcer within 3 months prior to first randomization. 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
•malignancy within 5 years of first randomization, with the exception of basal cell carcinoma treated by complete excision
•lymphoproliferative disease or previous total lymphoid irradiation
•severe viral infection (CMV, HBV, HCV) within 3 months of first randomization; or known HIV infection
9. Other known clinically significant active medical conditions, such as:
•severe cardiovascular disease including CHF
•liver dysfunction [aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin greater than 2.5 times the upper limit of normal] measured on at least 2 separate occasions
•COPD, or asthma requiring oral steroids
•bone marrow insufficiency unrelated to active SLE (according to investigator judgment) with white blood cell count (WBC) <2500/mm3; absolute neutrophil count (ANC) <1.3 x 103/µL; thrombocytopenia (platelet count) <50,000/mm3
•active bleeding disorders
•current infection requiring IV antibiotics
10. Any overlapping autoimmune condition for which the condition or 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.
11. Other major physical or psychiatric illness or major traumatic injury within 6 months prior to first randomization
12. Other medical condition which, in the investigator’s judgment, may be associated with increased risk to the subject or may interfere with study assessments or outcomes
13.Participation in another clinical trial and/or receipt of investigational drugs within 4 weeks prior to screening visit
14. Use of medications prohibited prior to first randomization
Maintenance Phase:
1. Does not meet maintenance phase inclusion criteria.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method