Efficacy and Safety of Enteric-coated Mycophenolate Sodium in Combination With Two Corticosteroid Regimens for the Treatment of Lupus Nephritis Flare

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00423098
• Collaborator: (none)
• Enrollment: 81
• Locations: 17
• Arms: 2
• Duration (Months): 33
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study will investigate the efficacy and safety of enteric-coated mycophenolate sodium in combination with two different corticosteroid (CS) regimes for the induction of remission of a lupus nephritis flare. Patients will be randomly allocated to standard CS regimen (group I) or to a reduced dose CS regimen (group II)

Condition or Disease	Intervention/Treatment	Phase
Lupus Nephritis	Drug: Mycophenolate sodium; Drug: Prednisone; Drug: Methylprednisolone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter, Open-label, 6-month Study to Explore the Efficacy and Safety of Enteric-coated Mycophenolate Sodium in Combination With Two Corticosteroid Regimens for the Treatment of Lupus Nephritis Flare
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Standard dose Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of Prednisone was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Drug: Mycophenolate sodium; Mycophenolate sodium as administered orally for 2 weeks at 1440mg daily and then increased to 2160mg daily for 22 weeks.; Other Names: Myfortic ; Drug: Prednisone; Oral prednisone or prednisone equivalent was started on Day 4 and subsequently tapered every 2 weeks according to the patient's weight.; Drug: Methylprednisolone; All patients received bolus therapy with 0.5 g of intravenous Methylprednisolone per day for 3 consecutive days.
Active Comparator: Low dose Mycophenolate sodium was administered in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of Prednisone was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Drug: Mycophenolate sodium; Mycophenolate sodium as administered orally for 2 weeks at 1440mg daily and then increased to 2160mg daily for 22 weeks.; Other Names: Myfortic ; Drug: Prednisone; Oral prednisone or prednisone equivalent was started on Day 4 and subsequently tapered every 2 weeks according to the patient's weight.; Drug: Methylprednisolone; All patients received bolus therapy with 0.5 g of intravenous Methylprednisolone per day for 3 consecutive days.

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Complete Remission [24 Weeks]

   Complete remission was defined as urine protein/urine creatinine ratio < 0.5 gram urine protein per gram urine creatinine, urine sediment normalized (no cellular casts, < 5 red cells per high power field), and serum creatinine within 10% of normal range according to local lab.

Secondary Outcome Measures

1. Number of Patients With Complete Remission [12 Weeks]

   Complete remission was defined as urine protein/urine creatinine ratio < 0.5 gram urine protein per gram urine creatinine, urine sediment normalized (no cellular casts, < 5 red cells per high power field), and serum creatinine within 10% of normal value.

2. Number of Patients With Partial Remission [Baseline to 12 and 24 weeks]

   Partial remission was defined as urine protein/creatinine ratio reduced by at least 50% from baseline and stable serum creatinine within 10% of baseline value) or improved.

3. Cumulative Dose of Prednisone Equivalent Corticosteroids (CS) [12 Weeks and 24 Weeks]

   Corticosteroid use was measured as cumulative dose until 12 and 24 weeks of treatment as well as daily doses at baseline, 12 and 24 weeks.

4. Number of Patients With Moderate to Severe Flares [12 and 24 weeks]

   A moderate to severe flare was defined as the occurrence of increased lupus activity after partial or complete remission, based on the presence of 1 BILAG A score or >=3 BILAG B scores. British Isles Lupus Assessment Group (BILAG) index divides lupus activity in 8 organs/systems which are each given a score of A to E. A=disease sufficiently active to need disease modifying treatment; B=problems requiring symptomatic treatment; C=mild stable disease; D=previously affected but currently inactive system; E=the system or organ has never been involved. BILAG score: A=9, B=3, C=1, D/E=0; range(0-72)

5. Duration of Exposure to Study Medication [24 weeks]

   The duration of exposure was calculated as the date of the last Mycophenolate sodium dose minus the date of the last Mycophenolate sodium dose +1.

6. Number of Patients With Adverse Events and Infections [24 weeks]

   Safety assessments included collecting all adverse events (AEs), serious adverse events (SAEs), with their severity and relationship to study drug. According to FDA 21CFR 314.80, a serious adverse event (SAE) is described as any adverse event that leads to death, is life threatening ( NIH criteria Grade 4), causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.

7. Number of Patients With Treatment Failure [12 Weeks and 24 Weeks]

   Treatment failure was defined as no therapeutic response (without complete or partial remission) or premature discontinuation during the first 24 weeks from study medication or the study for any reason except complete or partial remission.

8. Change From Baseline in Overall Disease Activity With Systematic Lupus Erythematosus Disease Activity Index (SLEDAI) [From Baseline to week 4, week 12 and week 24]

   SLEDAI stands for Systemic Lupus Erythematosus Disease Activity Index and was a well established global score index based on assessment of 24 items measuring a disease activity in the 10-day period prior to the assessment. SLEDAI item weights range from 1 for fever to 8 for seizures. A maximum theoretical score is 105. Total score range from 1 to 105. A flare has been defined as a SLEDAI score increase of 3 or more to a level of 8 or higher. During flares SLEDAI scores of 25 to 30 are common.

9. Change From Baseline in Overall Disease Activity With British Isles Lupus Assessment Group (BILAG) [From Baseline to week 4, week 12 and week 24]

   BILAG (British Isles Lupus Assessment Group) index divides lupus activity into 8 organs/systems and was based on the principle of the physician's intention to treat, assessing activity in the previous one month. Each organ or system was given a score of A to E, where A = disease that is sufficiently active to require disease modifying treatment; a B = problems requiring symptomatic treatment; C = stable mild disease; D = previously affected but currently inactive system; and E = the system or organ has never been involved. [A=9, B=3, C=1, D/E=0 the score range for each patient will be 0-72].

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria

• Male or female patients with systemic lupus erythematosus (SLE)(at least 4 classification criteria)

• Aged ≥18 years,

• Proliferative lupus nephritis classified as ISN/RPS class III or IV

• Renal biopsy within the last 24-month preceding the study entry

• Proteinuria defined as >0.5 gram urine protein per gram urine creatinine at screening and baseline

• Clinical activity defined by one or more of the following changes in renal function: Serum creatinine >1.0 mg/dl (88.4 μmol/l)

• Microscopic hematuria defined as >5 red cells per high power field

• Presence of cellular casts

Exclusion criteria

• Patients with calculated creatinine clearance <30 ml/min (using the Cockcroft-Gault formula)

• Patients having received an intravenous (i.v.) corticosteroid bolus during the last 3 months,

• Patients having received oral or i.v. cyclophosphamide during the last 3 month

• Patients having received mycophenolate mofetil (MMF) within the preceding 3 months

• Use of any antibody therapy within the past 6 months

• Pregnant or nursing (lactating) women or women of child-bearing potential who are planning to become pregnant, or are not willing to use effective means of contraception throughout the study and during one month after the end of the study.

• Use of other investigational drugs within 1 month of enrollment (except for antibodies: within 6 months of enrollment

• History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures,

• History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis	Bogota		Colombia
2	Novartis	Creteil		France
3	Novartis	Nantes		France
4	Novartis Investigative Site	Paris		France
5	Novartis	Berlin		Germany
6	Novartis	Tubingen		Germany
7	Novartis	Athens		Greece
8	Novartis	Budapest		Hungary
9	Novartis	Debrecen		Hungary
10	Novartis	Brescia		Italy
11	Novartis	Ferrara		Italy
12	Novartis	Milano		Italy
13	Novartis	Padova		Italy
14	Novartis	Barcelona		Spain
15	Novartis	Madrid		Spain
16	Novartis	Taichung		Taiwan
17	Novartis	Cambridge		United Kingdom

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00423098
• Other Study ID Numbers: CERL080A2420
• First Posted: Jan 17, 2007
• Last Update Posted: Jun 28, 2011
• Last Verified: May 1, 2011

• Keywords provided by , ,: Lupus Nephritis; enteric-coated mycophenolate sodium; EC-MPS; Myfortic
• Additional relevant MeSH terms: Nephritis; Lupus Nephritis; Mycophenolic Acid; Prednisone; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Study Results

Participant Flow

Arm/Group Title	Standard Dose	Low Dose
Arm/Group Description	Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Mycophenolate sodium was administered orally in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
Period Title: Overall Study
STARTED	42	39
COMPLETED	39	35
NOT COMPLETED	3	4

Baseline Characteristics

Arm/Group Title	Standard Dose	Low Dose	Total
Arm/Group Description	Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Mycophenolate sodium was administered orally in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Total of all reporting groups
Overall Participants	42	39	81
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.2 (8.53)	34.2 (10.74)	33.1 (9.65)
Age, Customized (participants) [Number]
18-29 years	20 47.6%	18 46.2%	38 46.9%
30-39 years	16 38.1%	10 25.6%	26 32.1%
40-49 years	4 9.5%	6 15.4%	10 12.3%
50-59 years	2 4.8%	4 10.3%	6 7.4%
>=60 years	0 0%	1 2.6%	1 1.2%
Sex: Female, Male (Count of Participants)
Female	37 88.1%	29 74.4%	66 81.5%
Male	5 11.9%	10 25.6%	15 18.5%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Complete Remission
Description	Complete remission was defined as urine protein/urine creatinine ratio < 0.5 gram urine protein per gram urine creatinine, urine sediment normalized (no cellular casts, < 5 red cells per high power field), and serum creatinine within 10% of normal range according to local lab.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population: All randomized patients who received at least one dose of study drug.

Arm/Group Title	Standard Dose	Low Dose
Arm/Group Description	Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Mycophenolate sodium was administered orally in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
Measure Participants	42	39
Yes	8 19%	8 20.5%
No	34 81%	31 79.5%

2. Secondary Outcome

Title	Number of Patients With Complete Remission
Description	Complete remission was defined as urine protein/urine creatinine ratio < 0.5 gram urine protein per gram urine creatinine, urine sediment normalized (no cellular casts, < 5 red cells per high power field), and serum creatinine within 10% of normal value.
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population: All randomized patients who received at least one dose of study drug.

Arm/Group Title	Standard Dose	Low Dose
Arm/Group Description	Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Mycophenolate sodium was administered orally in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
Measure Participants	42	39
Yes	9 21.4%	5 12.8%
No	33 78.6%	34 87.2%

3. Secondary Outcome

Title	Number of Patients With Partial Remission
Description	Partial remission was defined as urine protein/creatinine ratio reduced by at least 50% from baseline and stable serum creatinine within 10% of baseline value) or improved.
Time Frame	Baseline to 12 and 24 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population: All randomized patients who received at least one dose of study drug.

Arm/Group Title	Standard Dose	Low Dose
Arm/Group Description	Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Mycophenolate sodium was administered orally in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
Measure Participants	42	39
At 12 weeks - Yes	16 38.1%	11 28.2%
At 12 weeks - No	26 61.9%	28 71.8%
At 24 weeks - Yes	20 47.6%	14 35.9%
At 24 weeks - No	22 52.4%	25 64.1%

4. Secondary Outcome

Title	Cumulative Dose of Prednisone Equivalent Corticosteroids (CS)
Description	Corticosteroid use was measured as cumulative dose until 12 and 24 weeks of treatment as well as daily doses at baseline, 12 and 24 weeks.
Time Frame	12 Weeks and 24 Weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population: All randomized patients who received at least one dose of study drug.

Arm/Group Title	Standard Dose	Low Dose
Arm/Group Description	Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Mycophenolate sodium was administered orally in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
Measure Participants	42	39
Week 12	106.1 (13.55)	68.2 (16.41)
Week 24	114.2 (15.01)	73.0 (17.76)

5. Secondary Outcome

Title	Number of Patients With Moderate to Severe Flares
Description	A moderate to severe flare was defined as the occurrence of increased lupus activity after partial or complete remission, based on the presence of 1 BILAG A score or >=3 BILAG B scores. British Isles Lupus Assessment Group (BILAG) index divides lupus activity in 8 organs/systems which are each given a score of A to E. A=disease sufficiently active to need disease modifying treatment; B=problems requiring symptomatic treatment; C=mild stable disease; D=previously affected but currently inactive system; E=the system or organ has never been involved. BILAG score: A=9, B=3, C=1, D/E=0; range(0-72)
Time Frame	12 and 24 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population: All randomized patients who received at least one dose of study drug.

Arm/Group Title	Standard Dose	Low Dose
Arm/Group Description	Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Mycophenolate sodium was administered orally in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
Measure Participants	42	39
At week 12 - Yes	0 0%	0 0%
At week 12 - No	42 100%	39 100%
At week 24 - Yes	1 2.4%	0 0%
At week 24 - No	41 97.6%	39 100%

6. Secondary Outcome

Title	Duration of Exposure to Study Medication
Description	The duration of exposure was calculated as the date of the last Mycophenolate sodium dose minus the date of the last Mycophenolate sodium dose +1.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Safety population: All patients who received at least one dose of study drug and had at least one post-baseline safety assessment.

Arm/Group Title	Standard Dose	Low Dose
Arm/Group Description	Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Mycophenolate sodium was administered orally in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
Measure Participants	42	39
Mean (Standard Deviation) [days]	164.5 (24.87)	157.7 (41.15)

7. Secondary Outcome

Title	Number of Patients With Adverse Events and Infections
Description	Safety assessments included collecting all adverse events (AEs), serious adverse events (SAEs), with their severity and relationship to study drug. According to FDA 21CFR 314.80, a serious adverse event (SAE) is described as any adverse event that leads to death, is life threatening ( NIH criteria Grade 4), causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Safety population: All patients who received at least one dose of study drug and had at least one post-baseline safety assessment.

Arm/Group Title	Standard Dose	Low Dose
Arm/Group Description	Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Mycophenolate sodium was administered orally in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
Measure Participants	42	39
At least one adverse event	35 (5.63) 83.3%	30 (6.62) 76.9%
Any severe adverse event	7 (7.08) 16.7%	3 (8.31) 7.7%
Any drug related adverse event	18 (7.32) 42.9%	16 (8.35) 41%
Any serious adverse event	8 19%	4 10.3%
Any infection	25 59.5%	17 43.6%
Any severe infection	3 7.1%	1 2.6%
Any drug related infection	10 23.8%	6 15.4%
Any serious infection	4 9.5%	1 2.6%

8. Secondary Outcome

Title	Number of Patients With Treatment Failure
Description	Treatment failure was defined as no therapeutic response (without complete or partial remission) or premature discontinuation during the first 24 weeks from study medication or the study for any reason except complete or partial remission.
Time Frame	12 Weeks and 24 Weeks

Outcome Measure Data

Analysis Population Description

Safety Population: All patients who received at least one dose of study drug and had at least one post-baseline safety assessment.

Arm/Group Title	Standard Dose	Low Dose
Arm/Group Description	Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Mycophenolate sodium was administered orally in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
Measure Participants	42	39
At 12 weeks - Yes	23 54.8%	25 64.1%
At 12 weeks - No	19 45.2%	14 35.9%
At 24 weeks - Yes	21 50%	22 56.4%
At 24 weeks - No	21 50%	17 43.6%

9. Secondary Outcome

Title	Change From Baseline in Overall Disease Activity With Systematic Lupus Erythematosus Disease Activity Index (SLEDAI)
Description	SLEDAI stands for Systemic Lupus Erythematosus Disease Activity Index and was a well established global score index based on assessment of 24 items measuring a disease activity in the 10-day period prior to the assessment. SLEDAI item weights range from 1 for fever to 8 for seizures. A maximum theoretical score is 105. Total score range from 1 to 105. A flare has been defined as a SLEDAI score increase of 3 or more to a level of 8 or higher. During flares SLEDAI scores of 25 to 30 are common.
Time Frame	From Baseline to week 4, week 12 and week 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all randomized patients who received at least one dose of study drug. Only patients with assessments at both baseline and post-baseline visits are summarized.

Arm/Group Title	Standard Dose	Low Dose
Arm/Group Description	Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Mycophenolate sodium was administered orally in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
Measure Participants	42	39
Change from Baseline to Week 4: (N= 39, 37)	-7.4 (5.63)	-7.7 (6.62)
Change from Baseline to Week 12: (N= 41, 35)	-9.7 (7.08)	-10.3 (8.31)
Change from Baseline to Week 24: (N= 39, 34)	-10.3 (7.32)	-9.8 (8.35)

10. Secondary Outcome

Title	Change From Baseline in Overall Disease Activity With British Isles Lupus Assessment Group (BILAG)
Description	BILAG (British Isles Lupus Assessment Group) index divides lupus activity into 8 organs/systems and was based on the principle of the physician's intention to treat, assessing activity in the previous one month. Each organ or system was given a score of A to E, where A = disease that is sufficiently active to require disease modifying treatment; a B = problems requiring symptomatic treatment; C = stable mild disease; D = previously affected but currently inactive system; and E = the system or organ has never been involved. [A=9, B=3, C=1, D/E=0 the score range for each patient will be 0-72].
Time Frame	From Baseline to week 4, week 12 and week 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) populationincluded all randomized patients who received at least one dose of study drug. Only patients with assessments at both baseline and post-baseline visits are summarized.

Arm/Group Title	Standard Dose	Low Dose
Arm/Group Description	Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.	Mycophenolate sodium was administered orally in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
Measure Participants	42	39
Change from baseline Week 4: (N= 40, 37)	-4.8 (5.34)	-5.5 (6.50)
Change from baseline Week 12: (N= 41, 35)	-8.6 (6.76)	-8.7 (6.19)
Change from baseline Week 24: (N= 40, 34)	-8.6 (5.79)	-9.4 (5.52)

Adverse Events

Arm/Group Title	Standard Dose		Low Dose
Arm/Group Description	Mycophenolate sodium was administered orally in combination with a standard dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 1 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.		Mycophenolate sodium was administered orally in combination with a reduced dose of corticosteroids (CS) administered as prednisone or prednisone equivalent (PRED). Mycophenolate sodium was administered in divided doses at a daily dose of 1440 mg during the first 2 weeks of the study and then at 2160 mg daily for the next 22 weeks. The dose of CS was started at 0.5 mg per kg body weight and subsequently tapered according to the patient's weight. The planned treatment duration was 24 weeks.
All Cause Mortality
	Standard Dose		Low Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard Dose		Low Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/42 (19%)		4/39 (10.3%)
Gastrointestinal disorders
Diarrhoea	1/42 (2.4%)		0/39 (0%)
Pancreatitis acute	1/42 (2.4%)		0/39 (0%)
Vomiting	1/42 (2.4%)		0/39 (0%)
General disorders
Death	1/42 (2.4%)		0/39 (0%)
Mucosal inflammation	1/42 (2.4%)		0/39 (0%)
Multi-organ failure	1/42 (2.4%)		0/39 (0%)
Oedema peripheral	1/42 (2.4%)		0/39 (0%)
Infections and infestations
Cytomegalovirus infection	1/42 (2.4%)		0/39 (0%)
Epstein-barr virus infection	1/42 (2.4%)		0/39 (0%)
Gastroenteritis	1/42 (2.4%)		1/39 (2.6%)
Herpes zoster	1/42 (2.4%)		0/39 (0%)
Sinusitis	1/42 (2.4%)		0/39 (0%)
Injury, poisoning and procedural complications
Fall	0/42 (0%)		1/39 (2.6%)
Tendon rupture	1/42 (2.4%)		1/39 (2.6%)
Nervous system disorders
Headache	0/42 (0%)		1/39 (2.6%)
Syncope	0/42 (0%)		1/39 (2.6%)
Renal and urinary disorders
Renal failure acute	1/42 (2.4%)		0/39 (0%)
Respiratory, thoracic and mediastinal disorders
Dysphonia	1/42 (2.4%)		0/39 (0%)
Vascular disorders
Hypertension	1/42 (2.4%)		1/39 (2.6%)
Other (Not Including Serious) Adverse Events
	Standard Dose		Low Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/42 (66.7%)		18/39 (46.2%)
Blood and lymphatic system disorders
Anaemia	1/42 (2.4%)		3/39 (7.7%)
Cardiac disorders
Tachycardia	1/42 (2.4%)		2/39 (5.1%)
Gastrointestinal disorders
Abdominal pain upper	1/42 (2.4%)		3/39 (7.7%)
Constipation	3/42 (7.1%)		1/39 (2.6%)
Diarrhoea	9/42 (21.4%)		8/39 (20.5%)
Gastritis	0/42 (0%)		2/39 (5.1%)
Nausea	3/42 (7.1%)		1/39 (2.6%)
Vomiting	3/42 (7.1%)		4/39 (10.3%)
General disorders
Oedema peripheral	4/42 (9.5%)		5/39 (12.8%)
Infections and infestations
Folliculitis	0/42 (0%)		2/39 (5.1%)
Herpes zoster	6/42 (14.3%)		0/39 (0%)
Nasopharyngitis	4/42 (9.5%)		1/39 (2.6%)
Upper respiratory tract infection	4/42 (9.5%)		2/39 (5.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/42 (9.5%)		5/39 (12.8%)
Muscle spasms	3/42 (7.1%)		1/39 (2.6%)
Musculoskeletal stiffness	0/42 (0%)		2/39 (5.1%)
Psychiatric disorders
Insomnia	4/42 (9.5%)		4/39 (10.3%)
Respiratory, thoracic and mediastinal disorders
Cough	3/42 (7.1%)		2/39 (5.1%)
Vascular disorders
Hypertension	2/42 (4.8%)		2/39 (5.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.