A Study to Evaluate the Efficacy and Safety of Sifalimumab in Adults With Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

Official title:

A Phase 2b, Dose-ranging Study to Evaluate the Efficacy and Safety of Sifalimumab in Adults With Systemic Lupus Erythematosus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01283139
• Other study ID #: CD-IA-MEDI-545-1067
• Secondary ID: 2010-024069-30
• Status: Completed
• Phase: Phase 2
• First received: January 20, 2011
• Last updated: March 23, 2018
• Start date: March 31, 2011
• Est. completion date: April 17, 2014

Study information

• Verified date: March 2018
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the efficacy and safety of sifalimumab compared to placebo in subjects with moderately to severely active Systemic Lupus Erythematosus (SLE).

Description:

This is a Phase 2b, multinational, multicenter, randomized, double-blind, placebo controlled, parallel group study to evaluate the efficacy and safety of three intravenous (IV) treatment regimens of sifalimumab (200, 600, or 1,200 mg) in adult subjects with chronic moderately-to-severely active SLE with an inadequate response to standard of care (SOC) for SLE.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 834
• Est. completion date: April 17, 2014
• Est. primary completion date: November 14, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria: - Fulfills at least 4 of American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) including a positive antinuclear antibody (ANA) or elevated ds-deoxyribonucleic acid (DNA) or Sm antibody at screening - Disease history of SLE greater than or equal to (>=) 24 weeks at screening - Weight more than (>) 40 kilogram (kg) - Currently receiving stable dose of oral prednisone and/or antimalarials/immunosuppressives - Active moderate to severe SLE disease based on SLE disease activity score (SLEDAI) and British Isles Lupus Assessment Group Index (BILAG) and Physicians Global Assessment - No evidence of cervical malignancy on PAP within 6 months of randomization - Female subjects must be willing to avoid pregnancy - Negative TB test or newly positive TB test due to latent TB for which treatment must be initiated at or before randomization. Exclusion Criteria: - Active severe SLE-driven renal disease or unstable renal disease prior to screening - Active severe or unstable neuropsychiatric SLE - Clinically significant active infection including ongoing and chronic infections - History of human immunodeficiency virus (HIV) - Confirmed Positive tests for Hepatitis B or positive test for hepatitis C - History of severe herpes infection such as herpes encephalitis, ophthalmic herpes, disseminated herpes - Herpes Zoster within 3 months of screening - History of cancer other than basal cancer or cervical cancer treated with apparent success >=1 year prior to randomization - Receipt of a biologic agent within 5 half-lives or prior to loss of pharmacodynamic and/or clinical effect (whichever is longer) prior to screening - Live or attenuated vaccine within 4 weeks prior to screening - Subjects with substance abuse - Subjects with significant hematologic abnormalities.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Biological:
• Sifalimumab 200 mg
Sifalimumab 200 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.
• Sifalimumab 600 mg
Sifalimumab 600 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.
• Sifalimumab 1,200 mg
Sifalimumab 1,200 mg intravenously every 2 weeks for 4 weeks and then monthly for 44 weeks for a total of 14 doses.

Other:
• Placebo
IV Placebo every 2 weeks for 4 weeks and then monthly for 44 weeks

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Ciudad Autonoma de Buenos Aire
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	La Plata
Argentina	Research Site	Quilmes
Argentina	Research Site	San Miguel de Tucuman
Argentina	Research Site	Tucuman
Brazil	Research Site	Curitiba
Brazil	Research Site	Goiania
Brazil	Research Site	Juiz de Fora
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Salvador
Brazil	Research Site	Sao Paulo
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Canada	Research Site	Quebec City	Quebec
Canada	Research Site	Sherbrooke	Quebec
Chile	Research Site	Osorno
Chile	Research Site	Santiago
Chile	Research Site	Viña del Mar
France	Research Site	Bordeaux Cedex
France	Research Site	LE KREMLIN-BICETRE Cedex
France	Research Site	Paris Cedex 13
France	Research Site	Strasbourg Cedex
Germany	Research Site	Berlin
Germany	Research Site	Dresden
Germany	Research Site	Frankfurt
Germany	Research Site	Kiel
Germany	Research Site	Köln
Germany	Research Site	Leipzig
Germany	Research Site	Mainz
Germany	Research Site	Münster
Germany	Research Site	Regensburg
Germany	Research Site	Würzburg
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Miskolc
Hungary	Research Site	Zalaegerszeg
India	Research Site	Bangalore
India	Research Site	Secunderabad
Italy	Research Site	Brescia
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Padova
Italy	Research Site	Pisa
Italy	Research Site	Roma
Jamaica	Research Site	Kingston
Mexico	Research Site	Chihuahua
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico
Mexico	Research Site	México
Mexico	Research Site	San Luis Potosi
Netherlands	Research Site	Amsterdam
Peru	Research Site	Lima
Peru	Research Site	San Borja
Philippines	Research Site	Cebu City
Philippines	Research Site	Iloilo City
Philippines	Research Site	Manila
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Katowice
Poland	Research Site	Kraków
Poland	Research Site	Lublin
Poland	Research Site	Olsztyn
Poland	Research Site	Poznan
Poland	Research Site	Warszawa
Romania	Research Site	Brasov
Romania	Research Site	Bucharest
Romania	Research Site	Bucuresti
Romania	Research Site	Cluj Napoca
Romania	Research Site	Tg Mures
South Africa	Research Site	Cape Town
South Africa	Research Site	Durban
South Africa	Research Site	Johannesburg
South Africa	Research Site	Pinelands
South Africa	Research Site	Soweto
Spain	Research Site	Barcelona
Spain	Research Site	Guadalajara
Spain	Research Site	La Laguna (Tenerife)
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Malaga
Spain	Research Site	Mérida
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Sevilla
Thailand	Research Site	Bangkok
United Kingdom	Research Site	Brighton
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Cannock
United Kingdom	Research Site	Guildford
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United States	Research Site	Baltimore	Maryland
United States	Research Site	Brooklyn	New York
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Dallas	Texas
United States	Research Site	Fort Lauderdale	Florida
United States	Research Site	Idaho Falls	Idaho
United States	Research Site	La Jolla	California
United States	Research Site	Lansing	Michigan
United States	Research Site	Manhasset	New York
United States	Research Site	New York	New York
United States	Research Site	Orlando	Florida
United States	Research Site	Palm Desert	California
United States	Research Site	Raleigh	North Carolina
United States	Research Site	San Leandro	California
United States	Research Site	Seattle	Washington
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Stockbridge	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Canada,  Chile,  France,  Germany,  Hungary,  India,  Italy,  Jamaica,  Mexico,  Netherlands,  Peru,  Philippines,  Poland,  Romania,  South Africa,  Spain,  Thailand,  United Kingdom, 

References & Publications (1)

Khamashta M, Merrill JT, Werth VP, Furie R, Kalunian K, Illei GG, Drappa J, Wang L, Greth W; CD1067 study investigators. Sifalimumab, an anti-interferon-a monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2016 Nov;75(11):1909-1916. doi: 10.1136/annrheumdis-2015-208562. Epub 2016 Mar 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving a Response in Systemic Lupus Erythematosus Responder Index 4 (SRI [4])	SRI (4) responder is defined as: 1) a reduction in baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity score of greater than or equal to (>=) 4 points (with increased deoxyribonucleic acid [DNA] binding item of SLEDAI-2K score based on the ANA Multi-Lyte® ANA-II Plus Test System); 2) no worsening in Physician Global Assessment (MDGA) (worsening is defined as an increase of >=0.3 from baseline on a 0-3 visual analogue scale) and 3) no worsening in British Isles Lupus Assessment Group (BILAG-2004) (worsening is defined as at least 1 new 'A' score or 2 new 'B' scores on the BILAG-2004 compared with baseline).	Day 365
Primary	Percentage of Participants Achieving a Positive Response in SRI (4) in 4-Gene Interferon Test High Participants	SRI (4) responder is defined as: 1) a reduction in baseline SLEDAI-2K disease activity score of >=4 points (with increased DNA binding item of SLEDAI-2K score based on the ANA Multi-Lyte® ANA-II Plus Test System); 2) no worsening in Physician Global Assessment (MDGA) (worsening is defined as an increase of >=0.3 from baseline on a 0-3 visual analogue scale) and 3) no worsening in BILAG-2004 (worsening is defined as at least 1 new 'A' score or 2 new 'B' scores on the BILAG-2004 compared with baseline).	Day 365
Secondary	Percentage of Participants on Greater Than or Equal to 10 mg/Day Oral Prednisone (or Equivalent) at Baseline Who Were Able to Reduce to Less Than or Equal to (<=) 7.5 mg/Day	Percentage of participants on >=10 mg/day oral corticosteroids (OCS) at baseline who were able to taper it to <=7.5 mg/day by Day 365 were recorded.	Day 365
Secondary	Percentage of Participants With a Cutaneous Lupus Erythematosus Disease Activity and Severity Index (CLASI) Activity Score Greater Than or Equal to (>=) 10 at Baseline Who Achieved a >= 4-point Reduction	The CLASI consists of two scores, the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. Damage is scored in terms of dyspigmentation and scarring, including scarring alopecia. The percentage of participants with a CLASI activity score >=10 at baseline who achieved a clinically significant (>=4-point) reduction at Day 365 were reported.	Day 365
Secondary	Percentage of Participants Who Achieved a Greater Than 3-Point Improvement in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale	FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).	Day 365
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent defined as events present at baseline that worsened in intensity after administration of investigational product or events absent at baseline that emerged after administration of investigational product, for the period extending until the end of participant participation in the study.	Day 1 up to Week 74
Secondary	Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)	Laboratory investigations included hematology, serum chemistries and urinalysis parameters. Participants with clinically significant abnormalities in these laboratory investigations recorded as TEAEs were reported.	Day 1 up to Week 61
Secondary	Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)	Vital sign assessments included blood pressure, pulse rate, temperature, weight and respiratory rate. Vital signs abnormalities recorded as TEAEs were reported.	Day 1 up to Week 61
Secondary	Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as TEAEs	The 12-lead ECG data were summarized and evaluated. Number of participants with clinically significant abnormal ECG findings as assessed by cardiologist were recorded and reported as TEAEs.	Day 1 up to Week 56

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