Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01499355




Trial ID
NCT01499355
Ethics application status
Date submitted
23/11/2011
Date registered
22/12/2011
Date last updated
22/11/2016

Titles & IDs
Public title
BIIB023 Proof-of-Concept Study in Participants With Lupus Nephritis
Scientific title
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of BIIB023 in Subjects With Lupus Nephritis
Secondary ID [1] 0 0
2011-002159-32
Secondary ID [2] 0 0
211LE201
Universal Trial Number (UTN)
Trial acronym
ATLAS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lupus Nephritis 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - BIIB023
Other interventions - Placebo
Treatment: Drugs - mycophenolate mofetil
Treatment: Drugs - oral corticosteroids

Placebo Comparator: Placebo - Placebo intravenous (IV) infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and mycophenolate mofetil (MMF)

Experimental: BIIB023 3 mg/kg - BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.

Experimental: BIIB023 20 mg/kg - BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.


Other interventions: BIIB023


Other interventions: Placebo


Treatment: Drugs: mycophenolate mofetil
titrated to a target daily dose of 2 g (1 g twice daily)

Treatment: Drugs: oral corticosteroids
oral corticosteroids (prednisone or equivalent) at a target prednisone dose of 10 mg/day

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Achieve a Complete or Partial Renal Response at Week 52 - Complete renal response is defined as: (1) urinary protein:creatinine ratio (uPCR) < 0.5 mg/mg with = 50% reduction of uPCR from Day 1 (Baseline; from a 24 hour urine collection); and (2) estimated glomerular filtration rate (eGFR) within normal range. Partial renal response is defined as: (1) = 50% reduction in uPCR from Day 1 (Baseline; from a 24-hour urine collection) and, (2) with one of the following: (a) uPCR of < 1.0 mg/mg if the Day 1 (Baseline) was = 3.0 mg/mg, or, (b) uPCR < 3.0 mg/mg if the Day 1 (Baseline) ratio was > 3.0 mg/mg; and stabilization of renal function (eGFR + or - 25% of Day 1 [Baseline] or serum creatinine within normal range).
Timepoint [1] 0 0
Week 52
Secondary outcome [1] 0 0
Percentage of Participants Who Achieve Complete Renal Response at Week 52 - Complete renal response is defined as uPCR < 0.5 mg/mg with = 50% reduction of uPCR from Baseline (from a 24-hour urine collection) and eGFR within normal range.
Timepoint [1] 0 0
Week 52
Secondary outcome [2] 0 0
Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 - Duration of response was calculated as the days in between the date of Week 52 visit and the date when the participant last became complete renal responder on or before Week 52 visit. Complete renal response: (1) uPCR <0.5 mg/mg with = 50% reduction of uPCR from Day 1 (Baseline) (from a 24 hour urine collection); and (2) eGFR within normal range.
Timepoint [2] 0 0
Week 52
Secondary outcome [3] 0 0
Time to Renal Response (Partial or Complete) in Participants Who Achieve Renal Response at Week 52 - Onset of renal response was calculated as weeks elapsed from baseline date to first visit where renal response was achieved. Complete renal response is defined as: (1) uPCR <0.5 mg/mg with = 50% reduction of uPCR from Day 1 (Baseline) (from a 24 hour urine collection); and (2) eGFR within normal range. Partial renal response is defined as: (1) = 50% reduction in uPCR from Day 1 (Baseline; from a 24-hour urine collection) and, (2) with one of the following: (a) uPCR of < 1.0 mg/mg if the Day 1 (Baseline) was = 3.0 mg/mg, or, (b) uPCR < 3.0 mg/mg if the Day 1 (Baseline) ratio was > 3.0 mg/mg; and stabilization of renal function (eGFR + or - 25% of Day 1 [Baseline] or serum creatinine within normal range). Estimated from the Kaplan-Meier Curve.
Timepoint [3] 0 0
Baseline to Week 52
Secondary outcome [4] 0 0
Percentage of Participants With uPCR > 3.0 mg/mg at Baseline Who Achieve uPCR <1.0 mg/mg at Week 52
Timepoint [4] 0 0
Baseline (Day 1), Week 52
Secondary outcome [5] 0 0
Percentage of Participants With Active Urinary Sediment at Baseline Who Have Inactive Urinary Sediment at Week 52 - Active urinary sediment is defined by 1 of the following (in the absence of a urinary tract infection or menses): > 5 red blood cell/high power field (RBC/HPF) or above the reference range for the laboratory, and > 5 white blood cell/high power field (WBC/HPF) or above the reference range for the laboratory, and presence of cellular casts (RBC or WBC). Inactive urinary sediment is defined as: < 5 RBC/HPF and < 5 WBC/HPF, or within the laboratory reference range, and no cellular casts (no RBC or WBC casts).
Timepoint [5] 0 0
Baseline, Week 52
Secondary outcome [6] 0 0
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period - AEs that had an onset on or after dosing of MMF on run-in Day 1 up to the first double-blind dose, or any pre-existing condition that worsened. AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above.
Timepoint [6] 0 0
Day 1 to Week 12
Secondary outcome [7] 0 0
Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period - AEs that had an onset on or after dosing of BIIB023 or placebo, or any pre-existing condition that worsened. AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above.
Timepoint [7] 0 0
Week 12 to Week 56
Secondary outcome [8] 0 0
Duration of Renal Response in Participants Who Achieve Partial or Complete Renal Response at Any Time During the Study - Number of days between first visit with response to last consecutive visit with partial or complete response. Complete renal response is defined as: (1) uPCR <0.5 mg/mg with = 50% reduction of uPCR from Day 1 (Baseline) (from a 24 hour urine collection); and (2) eGFR within normal range. Partial renal response is defined as: (1) = 50% reduction in uPCR from Day 1 (Baseline; from a 24-hour urine collection) and, (2) with one of the following: (a) uPCR of < 1.0 mg/mg if the Day 1 (Baseline) was = 3.0 mg/mg, or, (b) uPCR < 3.0 mg/mg if the Day 1 (Baseline) ratio was > 3.0 mg/mg; and stabilization of renal function (eGFR + or - 25% of Day 1 [Baseline] or serum creatinine within normal range). Estimated from the Kaplan-Meier Curve.
Timepoint [8] 0 0
up to Week 52

Eligibility
Key inclusion criteria
Key

- Documented diagnosis of systemic lupus erythematosus (SLE) according to current
American College of Rheumatology (ACR) criteria. At least 4 ACR criteria must be
documented, 1 of which must be a positive antinuclear antibody (ANA), anti Sm, or anti
dsDNA antibody.

- Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS)
2003 Class III or IV lupus nephritis with either active or active/chronic disease,
confirmed by biopsy within 3 months prior to Screening. Participants are permitted to
have co existing Class V lupus nephritis. If a renal biopsy has not been performed
within 3 months of the Screening Visit, one can be performed during the Screening
Period after all other eligibility criteria have been confirmed. The local
histological diagnosis must be confirmed by the central study pathologist.

- Must have proteinuria at Screening (from a 24 hour urine sample collection) defined as
urinary protein:creatinine ratio (uPCR) >1.0 mg/mg.

Key
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Retinitis, poorly-controlled seizure disorder, acute confusional state, myelitis,
stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and
resulting from SLE at Screening

- Estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m^2 (calculated using
the abbreviated Modification of Diet in Renal Disease equation) or the presence of
oliguria or end-stage renal disease requiring dialysis or transplantation

- Subjects requiring dialysis within 12 months prior to Screening

- History of renal transplant

- Treatment with any biologic B-cell-depleting therapy (e.g., anti-CD20 [rituximab],
anti-CD22 [epratuzumab], anti-BLyS/B-cell activating factor [e.g., briobacept,
belimumab] therapy), or TACI-Ig within 12 months prior to Run-in Day 1.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Argentina
State/province [10] 0 0
Ciudad Autonoma Buenos Aires
Country [11] 0 0
Argentina
State/province [11] 0 0
Tucuman
Country [12] 0 0
Argentina
State/province [12] 0 0
Cordoba
Country [13] 0 0
Argentina
State/province [13] 0 0
La Plata
Country [14] 0 0
Argentina
State/province [14] 0 0
San Juan
Country [15] 0 0
Belgium
State/province [15] 0 0
Leuven
Country [16] 0 0
Belgium
State/province [16] 0 0
Liege
Country [17] 0 0
Brazil
State/province [17] 0 0
Mato Grosso
Country [18] 0 0
Brazil
State/province [18] 0 0
Sao Paulo
Country [19] 0 0
Colombia
State/province [19] 0 0
Barranquilla
Country [20] 0 0
Colombia
State/province [20] 0 0
Bogota
Country [21] 0 0
Colombia
State/province [21] 0 0
Medelin
Country [22] 0 0
France
State/province [22] 0 0
Gironde
Country [23] 0 0
France
State/province [23] 0 0
Nord
Country [24] 0 0
France
State/province [24] 0 0
Paris 9
Country [25] 0 0
France
State/province [25] 0 0
Paris
Country [26] 0 0
Germany
State/province [26] 0 0
Mainz
Country [27] 0 0
Hong Kong
State/province [27] 0 0
Hong Kong
Country [28] 0 0
Hong Kong
State/province [28] 0 0
Shatin
Country [29] 0 0
Hungary
State/province [29] 0 0
Budapest
Country [30] 0 0
Hungary
State/province [30] 0 0
Debrecen
Country [31] 0 0
Italy
State/province [31] 0 0
Pisa
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Busan
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Gyeonggi-do
Country [34] 0 0
Malaysia
State/province [34] 0 0
Sarawak
Country [35] 0 0
Malaysia
State/province [35] 0 0
Ipoh
Country [36] 0 0
Malaysia
State/province [36] 0 0
Kuala Lumpur
Country [37] 0 0
Malaysia
State/province [37] 0 0
Pulau Pinang
Country [38] 0 0
Malaysia
State/province [38] 0 0
Selangor Darul Ehsan
Country [39] 0 0
Malaysia
State/province [39] 0 0
Selangor
Country [40] 0 0
Mexico
State/province [40] 0 0
Coahuila
Country [41] 0 0
Mexico
State/province [41] 0 0
Cuauhtemoc
Country [42] 0 0
Mexico
State/province [42] 0 0
Leon
Country [43] 0 0
Mexico
State/province [43] 0 0
Mexico City
Country [44] 0 0
Mexico
State/province [44] 0 0
San Luis Potosi
Country [45] 0 0
Peru
State/province [45] 0 0
Lima
Country [46] 0 0
Philippines
State/province [46] 0 0
Manila
Country [47] 0 0
Philippines
State/province [47] 0 0
Quezon City
Country [48] 0 0
Poland
State/province [48] 0 0
Lodz
Country [49] 0 0
Poland
State/province [49] 0 0
Wroclaw
Country [50] 0 0
Portugal
State/province [50] 0 0
Coimbra
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Moscow
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Saint Petersburg
Country [53] 0 0
Spain
State/province [53] 0 0
Sagunto
Country [54] 0 0
Thailand
State/province [54] 0 0
Bangkok

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the study is to assess the efficacy of BIIB023 as an add-on
treatment to background therapy compared with placebo in combination with background therapy
in the treatment of participants with active, biopsy-proven lupus nephritis. The secondary
objectives of this study are to assess the safety and tolerability of BIIB023 compared with
placebo in this study population.
Trial website
https://clinicaltrials.gov/show/NCT01499355
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries