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

Lupus Nephritis Clinical Trial

— ATLAS  

Official title:

A Multicenter, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of BIIB023 in Subjects With Lupus Nephritis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01499355
• Other study ID #: 211LE201
• Secondary ID: 2011-002159-32
• Status: Terminated
• Phase: Phase 2
• First received: November 23, 2011
• Last updated: July 28, 2016
• Start date: July 2012
• Est. completion date: December 2015

Study information

• Verified date: July 2016
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of HealthSouth Korea: Korea Food and Drug Administration (KFDA)Belgium: Federal Agency for Medicinal Products and Health ProductsBrazil: National Health Surveillance AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Malaysia: National Pharmaceutical Control BureauAustralia: Department of Health and Ageing Therapeutic Goods AdministrationHong Kong: Department of HealthColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosSerbia: Medicines and Medical Devices Agency of SerbiaThailand: Ministry of Public HealthSpain: Spanish Agency of MedicinesMexico: Federal Commission for Sanitary Risks ProtectionPortugal: National Pharmacy and Medicines InstituteColombia: National Institutes of HealthSouth Africa: Medicines Control CouncilMalaysia: Ministry of HealthThailand: Food and Drug AdministrationPeru: Instituto Nacional de SaludHungary: National Institute of PharmacyCanada: Health CanadaPhilippines: Bureau of Food and DrugsPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsUnited States: Food and Drug AdministrationPortugal: National Authority of Medicines and Health Products, IP (INFARMED)Turkey: Ministry of HealthArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaGermany: Paul-Ehrlich-InstitutRussia: Ministry of Health of the Russian FederationItaly: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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. Participants who complete this study through Week 52 will be offered the option to enter an Extension study under a separate protocol 211LE202 (NCT0193089).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 188
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

• 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. Subjects 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 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 (GFR) <30 mL/min per 1.73 m^2 (calculated using the abbreviated Modification of Diet in Renal Disease [MDRD] equation) or the presence of oliguria or end-stage renal disease [ESRD] 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/BAFF [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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Biological:
• BIIB023
Intravenous (IV) Infusion of BIIB023
• Placebo
Intravenous (IV) Infusion

Drug:
• Mycophenolate Mofetil
Mycophenolate mofetil titrated to a target daily dose of 2 g (1 g twice daily)

Locations

Country	Name	City	State
Argentina	Research Site	Capital Federal	Ciudad Autonoma Buenos Aires
Argentina	Research Site	Cipolletti
Argentina	Research Site	Ciudad Autonoma Buenos Aires
Argentina	Research Site	Ciudad Autonoma Buenos Aires
Argentina	Research Site	Cordoba
Argentina	Research Site	Cordoba
Argentina	Research Site	La Plata
Argentina	Research Site	San Juan
Argentina	Research Site	San Miguel de Tucuman	Tucuman
Argentina	Research Site	San Miguel de Tucuman	Tucuman
Argentina	Research Site	Santa Fe
Australia	Research Site	Parkville	Victoria
Belgium	Research Site	Leuven
Belgium	Research Site	Liege
Brazil	Research Site	Cuiaba	Mato Grosso
Brazil	Research Site	Porto Alegre	Rio Grande do Sul
Brazil	Research Site	Sao Paulo
Colombia	Research Site	Barranquilla
Colombia	Research Site	Bogota
Colombia	Research Site	Medelin
France	Research Site	Lillie	Nord
France	Research Site	Paris
France	Research Site	Paris 9
France	Research Site	Pessac Cedex	Gironde
Germany	Research Site	Aachen
Germany	Research Site	Mainz
Germany	Research Site	Muenchen
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	N.t.
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Italy	Research Site	Padova
Italy	Research Site	Pisa
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Gwangju
Korea, Republic of	Research Site	Gyeonggi-do
Malaysia	Research Site	Ipoh
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuantan	Pahang
Malaysia	Research Site	Kuching	Sarawak
Malaysia	Research Site	Pulau Pinang
Malaysia	Research Site	Selangor
Malaysia	Research Site	Selangor Darul Ehsan
Mexico	Research Site	Cuauhtemoc
Mexico	Research Site	Leon
Mexico	Research Site	Merida
Mexico	Research Site	Mexico	Distrito Federal
Mexico	Research Site	Saltillo	Coahuila
Mexico	Research Site	San Luis Potosi
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Philippines	Research Site	Manila
Philippines	Research Site	Quezon City
Poland	Research Site	Lodz
Poland	Research Site	Wroclaw
Portugal	Research Site	Coimbra
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Serbia	Research Site	Belgrade
Spain	Research Site	Sagunto
Spain	Research Site	Zaragoza
Thailand	Research Site	Bangkoknoi	Bangkok
Thailand	Research Site	Patumwan	Bangkok
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Columbus	Ohio
United States	Research Site	El Paso	Texas
United States	Research Site	Houston	Texas
United States	Research Site	La Jolla	California
United States	Research Site	Lake Success	New York
United States	Research Site	Memphis	Tennessee
United States	Research Site	Orlando	Florida
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Rochester	Minnesota
United States	Research site	St. Louis	Missouri
United States	Research Site	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Colombia,  France,  Germany,  Hong Kong,  Hungary,  Italy,  Korea, Republic of,  Malaysia,  Mexico,  Peru,  Philippines,  Poland,  Portugal,  Russian Federation,  Serbia,  Spain,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants who achieve a complete or partial renal response at Week 52	Complete renal response is defined as urinary protein:creatinine ratio (uPCR) <0.5 mg/mg with =50% reduction of uPCR from Baseline (from a 24-hour urine collection) and estimated glomerular filtration rate (eGFR) within normal range. Partial renal response is defined as =50% reduction in uPCR from Baseline with one of the following: a) uPCR of <1.0 mg/mg if the Baseline was = 3.0 mg/mg, or b) uPCR <3.0 mg/mg if the Baseline ratio was >3.0 mg/mg; and stabilization of renal function (eGFR ± 25% of Baseline or serum creatinine within normal range).	Baseline and Week 52	No
Secondary	Percentage of participants who achieve complete renal response at Week 52	Complete renal response is defined as urinary protein:creatinine ratio (uPCR) <0.5 mg/mg with = 50% reduction of uPCR from Baseline (from a 24-hour urine collection) and estimated glomerular filtration rate (eGFR) within normal range.	Baseline and Week 52	No
Secondary	Duration of response in participants who achieve complete renal response at week 52		Up to Week 64	No
Secondary	Percentage of participants uPCR >3.0 mg/mg at Baseline who achieve uPCR <1.0 mg/mg		Week 52	No
Secondary	Time to renal response (partial or complete) in participants who achieve renal response		Baseline to Week 52	No
Secondary	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 • Presence of cellular casts (RBC or WBC) Inactive urinary sediment defined as: • < 5 RBC/HPF and < 5 WBC/HPF, or within the laboratory reference range, and • no cellular casts (no RBC or WBC casts)	Week 52	No
Secondary	Number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs leading to study discontinuation		Up to Week 56	Yes
Secondary	Duration of renal response		Up to week 64	No