BIIB023 Proof-of-Concept Study in Participants With Lupus Nephritis

NCT01499355 | Terminated Phase 2 Results DMC

• 2 other identifiers: 211LE2012011-002159-32
• Study Type: interventional
• Target: 276
• Locations: 21 countries
• Sites: 58

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.

Conditions

Lupus Nephritis

Outcome Measures

Primary Outcomes (1)

• 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).

  Week 52

Secondary Outcomes (8)

• Percentage of Participants Who Achieve Complete Renal Response at Week 52

  Week 52

• Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52

  Week 52

• Time to Renal Response (Partial or Complete) in Participants Who Achieve Renal Response at Week 52

  Baseline to Week 52

• Percentage of Participants With uPCR > 3.0 mg/mg at Baseline Who Achieve uPCR <1.0 mg/mg at Week 52

  Baseline (Day 1), Week 52

• Percentage of Participants With Active Urinary Sediment at Baseline Who Have Inactive Urinary Sediment at Week 52

  Baseline, Week 52

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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)

Biological: Placebo; Drug: mycophenolate mofetil; Drug: oral corticosteroids

BIIB023 3 mg/kg

EXPERIMENTAL

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.

Biological: BIIB023; Drug: mycophenolate mofetil; Drug: oral corticosteroids

BIIB023 20 mg/kg

EXPERIMENTAL

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.

Biological: BIIB023; Drug: mycophenolate mofetil; Drug: oral corticosteroids

Interventions

BIIB023 BIOLOGICAL

BIIB023 20 mg/kg; BIIB023 3 mg/kg

Placebo BIOLOGICAL

Placebo

mycophenolate mofetil DRUG

titrated to a target daily dose of 2 g (1 g twice daily)

Also known as: MMF, Cellcept

BIIB023 20 mg/kg; BIIB023 3 mg/kg; Placebo

oral corticosteroids DRUG

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

BIIB023 20 mg/kg; BIIB023 3 mg/kg; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (58)

Research Site

Torrance, California, 90509, United States

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Orlando, Florida, 32806, United States

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Boston, Massachusetts, 02118, United States

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Rochester, Minnesota, United States

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Lake Success, New York, 11020, United States

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Chapel Hill, North Carolina, 27599-7025, United States

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Columbus, Ohio, 43210, United States

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Memphis, Tennessee, 38119, United States

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El Paso, Texas, 79905, United States

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Capital Federal, Ciudad Autonoma Buenos Aires, C1015ABO, Argentina

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Córdoba, Córdoba Province, 5000, Argentina

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San Miguel de Tucumán, Tucumán Province, 4000, Argentina

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Ciudad Autonoma Buenos Aires, Argentina

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La Plata, B1902COS, Argentina

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San Juan, 5402DIL, Argentina

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San Miguel de Tucumán, Argentina

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Melbourne, Victoria, 3050, Australia

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Cuiabá, Mato Grosso, 78048-902, Brazil

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São Paulo, São Paulo, 04027-000, Brazil

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Barranquilla, Colombia

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Bogotá, Colombia

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Medellín, Colombia

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Pessac, Gironde, 33604, France

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Lille, Nord, 59037, France

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Paris, 75651, France

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Paris, 94010, France

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Mainz, 55131, Germany

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Hong Kong, Hong Kong

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Shatin, Hong Kong

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Budapest, 1097, Hungary

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Debrecen, 4032, Hungary

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Pisa, 56126, Italy

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Kuching, Sarawak, 93586, Malaysia

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Ipoh, 30990, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Kuala Selangor, 43000, Malaysia

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Pulau Pinang, 10990, Malaysia

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Selangor Darul Ehsan, 41200, Malaysia

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Saltillo, Coahuila, 25000, Mexico

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Cuauhtémoc, 06090, Mexico

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León, 37000, Mexico

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Mexico City, 14000, Mexico

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San Luis Potosí City, 78240, Mexico

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Lima, Peru

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Manila, 1015, Philippines

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Quezon City, 1102, Philippines

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Lodz, 92-153, Poland

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Wroclaw, 50-417, Poland

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Coimbra, 3000-075, Portugal

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Moscow, 123182, Russia

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Saint Petersburg, 197022, Russia

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Busan, 602-715, South Korea

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Gyeonggi-do, 443-721, South Korea

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Sagunto, 46520, Spain

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Bangkoknoi, Bangkok, 10700, Thailand

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Patumwan, Bangkok, 10330, Thailand

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MeSH Terms

Conditions

Lupus Nephritis

Interventions

BIIB023; Mycophenolic Acid; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

Study was terminated based on the review of results following the prespecified, blinded futility analysis, which did not demonstrate sufficient efficacy to warrant continuation of the study. Study was not terminated based on safety considerations.

Results Point of Contact

• Title: Biogen Study Medical Director
• Organization: Biogen

clinicaltrials@biogen.com

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2011
• First Posted: December 26, 2011
• Study Start: July 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 18, 2017
• Results First Posted: January 18, 2017

Record last verified: 2016-11

Locations

DE (1); PE (1); PL (2); US (9); BE (2); IT (1); ES (1); TH (2); BR (2); FR (4); KR (2); AR (7); PH (2); CO (3); HK (2); PT (1); RU (2); HU (2); ME (5); AU (1); MY (6)