Clinical trial NCT02437890: A Phase II Study to Evaluate Safety and Efficacy of ALX-0061 in Subjects With Systemic Lupus Erythematosus
Official title: A Phase II Multicenter, Randomized, Double-blind, Placebo Controlled, Dose-range Finding Study to Evaluate the Safety and Efficacy of ALX-0061 Administered Subcutaneously in Subjects With Moderate to Severe Active Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lupus Erythematosus, Systemic
Lead sponsor: Ablynx, a Sanofi company
Sponsor class: INDUSTRY
First posted: 2015-05-08
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary objective:

To assess the efficacy and safety of different dose regimens of ALX-0061 administered subcutaneously (s.c.) to subjects with moderate to severe active, seropositive systemic lupus erythematosus (SLE) compared to placebo.

Secondary objectives:

To assess the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, flare rate, steroid reduction and health-related quality of life, with different dose regimens of ALX-0061.


Eligibility criteria: Inclusion Criteria:

1. Man or woman ≥ 18 years and \< 65 years of age
2. Have a diagnosis of SLE for at least 6 months prior to screening and fulfill the 1997 American College of Rheumatology (ACR) or 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria
3. Have moderate to severe active SLE
4. Have seropositive disease at screening
5. Subject must be at least on one or more of the treatments for SLE as listed in the protocol
6. Others as defined in the protocol

Exclusion Criteria:

1. Have an A score on the revised BILAG-2004 other than in the mucocutaneous and/or musculoskeletal system at screening and at baseline for the organ systems that can be clinically assessed
2. Have a systemic inflammatory disease other than SLE
3. Clinically significant infection treated or needing treatment
4. Any active or recurrent viral infection that based on the Investigator´s clinical assessment makes the subject unsuitable for the study
5. Have received prior therapy blocking the interleukin-6 (IL-6) pathway
6. Others as defined in the protocol

Primary outcomes:
measure: Number and Percentage of Subjects Who Achieved a Response at Week 24 According to the Modified British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (mBICLA) Score
timeFrame: At Week 24 visit
Secondary outcomes:
measure: Number and Percentage of Subjects With mBICLA Response at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Number and Percentage of Subjects With Modified Systemic Lupus Erythematosus Responder Index (mSRI-4) Response at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Number and Percentage of Subjects With mSRI-5 Response at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Number and Percentage of Subjects With mSRI-6 Response at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Number and Percentage of Subjects With mSRI-7 Response at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Number and Percentage of Subjects With mSRI-8 Response at Week 24 and Week 48.
timeFrame: At Week 24 and Week 48
measure: Change From Baseline in Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (mSLEDAI-2K) Score at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Number and Percentage of Subjects With BILAG-2004 Normal Improvement at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Number and Percentage of Subjects With BILAG-2004 Enhanced Improvement at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: BILAG-2004 Total Score at Baseline, Week 24 and Week 48
timeFrame: At Baseline, Week 24 and Week 48
measure: Number and Percentage of Subjects With BILAG-2004 Normal Improvement in Mucocutaneous System at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Number and Percentage of Subjects With BILAG-2004 Normal Improvement in Musculoskeletal System at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Number and Percentage of Subjects With Persistent Minimal or no Activity in 9 Organ Systems According to BILAG-2004 Systems Tally at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Change From Baseline in Physician's Global Assessment (PGA) at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Change From Baseline in Patient's Global Assessment at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Change From Baseline in Proteinuria at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Number of Subjects Who Were Treatment-emergent Urine Sediment Positive at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Change From Baseline in Serum Creatinine at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Change From Baseline in Creatinine Clearance Estimation (eGFR) at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Number of and Percentage Treatment Failures From Baseline to Week 24 and Week 48
timeFrame: From Baseline to Week 24 and Week 48
measure: Number and Percentage of Subjects Experiencing Severe Flares According to BILAG-2004 Flare Index From Baseline to Week 24 and Week 48
timeFrame: From Baseline to Week 24 and Week 48
measure: Number and Percentage of Subjects Experiencing Severe Flares According to mSLEDAI-2K Flare Index (mSFI) From Baseline to Week 24 and Week 48
timeFrame: From Baseline to Week 24 and Week 48
measure: Percent Change From Baseline in Daily Dose of Steroids at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Number and Percentage of Subjects Whose Daily Dose of Steroids Was Reduced Without Severe Flares During Weeks 40-48
timeFrame: Between Week 40 and Week 48
measure: Number and Percentage of Subjects Who Discontinued Prednisone (or Equivalent) by Week 48 Without Experiencing a Severe Flare
timeFrame: Up to and including Week 48
measure: Change From Baseline in Physical Component Scores of Short Form (36) Health Survey (SF-36) at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Change From Baseline in Mental Component Scores of SF-36 at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Change From Baseline in 28 Joint Count Swollenness (SJC28) Score at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Change From Baseline in 28 Joint Count Tenderness (TJC28) Score at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12, Week 24 and Week 48
timeFrame: At Week 12, Week 24 and Week 48
measure: Change From Baseline in CLASI Damage Score at Week 12, Week 24 and Week 48
timeFrame: At Week 12, Week 24 and Week 48
measure: ALX-0061 Serum Concentrations at Week 24 and Week 48
timeFrame: At Week 24 and Week 48
measure: Actual Values of Soluble Interleukin 6 Receptor (sIL-6R) Concentrations at Baseline, Week 24, and Week 48
timeFrame: At Baseline, Week 24, and Week 48
measure: Actual Values of C-reactive Protein (CRP) Concentrations at Baseline, Week 24, and Week 48
timeFrame: At Baseline, Week 24, and Week 48
measure: Actual Values of Fibrinogen Concentrations at Baseline, Week 24, and Week 48
timeFrame: At Baseline, Week 24, and Week 48
measure: Actual Values of Anti-double-stranded (ds) DNA Concentrations at Baseline, Week 24, and Week 48
timeFrame: at Baseline, Week 24, and Week 48
measure: Actual Values of Complement C3 Concentrations at Baseline, Week 24, and Week 48
timeFrame: At Baseline, Week 24, and Week 48
measure: Actual Values of Complement C4 Concentrations at Baseline, Week 24, and Week 48
timeFrame: At Baseline, Week 24, and Week 48
measure: Actual Values for Hemolytic Complement Component 50 (CH50) at Baseline, Week 24, and Week 48
timeFrame: At Baseline, Week 24, and Week 48
measure: Number and Percentage of Subjects Who Were Treatment-emergent (TE) Anti-drug Antibody (ADA) Positive
timeFrame: From first administration of ALX-0061 up to and including follow-up
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigator Site
state: Alabama
city: Glendale
country: United States
facility: Investigator Site
state: Arizona
city: Phoenix
country: United States
facility: Investigator Site
state: Arizona
city: Tucson
country: United States
facility: Investigator Site
state: Arizona
city: Artesia
country: United States
facility: Investigator Site
state: California
city: La Jolla
country: United States
facility: Investigator Site
state: California
city: La Palma
country: United States
facility: Investigator Site
state: California
city: Los Angeles
country: United States
facility: Investigator Site
state: California
city: Upland
country: United States
facility: Investigator Site
state: California
city: Aventura
country: United States
facility: Investigator Site
state: Florida
city: Clearwater
country: United States
facility: Investigator Site
state: Florida
city: Orlando
country: United States
facility: Investigator Site
state: Florida
city: Pinellas Park
country: United States
facility: Investigator Site
state: Florida
city: Atlanta
country: United States
facility: Investigator Site
state: Georgia
city: Stockbridge
country: United States
facility: Investigator Site
state: Georgia
city: Louisville
country: United States
facility: Investigator Site
state: Kentucky
city: Cumberland
country: United States
facility: Investigator Site
state: Maryland
city: Lansing
country: United States
facility: Investigator Site
state: Michigan
city: New York
country: United States
facility: Investigator Site
state: New York
city: New York
country: United States
facility: Investigator Site
state: New York
city: Smithtown
country: United States
facility: Investigator Site
state: New York
city: Syracuse
country: United States
facility: Investigator Site
state: New York
city: Charlotte
country: United States
facility: Investigator Site
state: North Carolina
city: Raleigh
country: United States
facility: Investigator Site
state: North Carolina
city: Pittsburgh
country: United States
facility: Investigator Site
state: Pennsylvania
city: Jackson
country: United States
facility: Investigator Site
state: Tennessee
city: Austin
country: United States
facility: Investigator Site
state: Texas
city: Houston
country: United States
facility: Investigator Site
state: Texas
city: Caba
country: Argentina
facility: Investigator Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigator Site
city: Ciudad Autónoma de Buenos Aire
country: Argentina
facility: Investigator Site
city: Córdoba
country: Argentina
facility: Investigator Site
city: San Juan
country: Argentina
facility: Investigator Site
city: Tucuman
country: Argentina
facility: Investigator Site
city: Santiago
country: Chile
facility: Investigator Site 1
city: Santiago
country: Chile
facility: Investigator Site 2
city: Prague
country: Czechia
facility: Investigator Site
city: Berlin
country: Germany
facility: Investigator Site
city: Dresden
country: Germany
facility: Investigator Site
city: Mainz
country: Germany
facility: Investigator Site
city: Mannheim
country: Germany
facility: Investigator Site
city: Budapest
country: Hungary
facility: Investigator Site 1
city: Budapest
country: Hungary
facility: Investigator Site 2
city: Debrecen
country: Hungary
facility: Investigator Site
city: Gyula
country: Hungary
facility: Investigator Site
city: Zalaegerszeg
country: Hungary
facility: Investigator Site
city: Daegu
country: Korea, Republic of
facility: Investigator Site
city: Gwangju
country: Korea, Republic of
facility: Investigator Site
city: Seoul
country: Korea, Republic of
facility: Investigator Site 1
city: Seoul
country: Korea, Republic of
facility: Investigator Site 2
city: Guadalajara
country: Mexico
facility: Investigator Site 1
city: Guadalajara
country: Mexico
facility: Investigator Site 2
city: Guadalajara
country: Mexico
facility: Investigator Site 3
city: Merida
country: Mexico
facility: Investigator Site
city: Mexicali
country: Mexico
facility: Investigator Site
city: Mexico City
country: Mexico
facility: Investigator Site
city: San Luis Potosi
country: Mexico
facility: Investigator Site
city: Lima
country: Peru
facility: Investigator Site 1
city: Lima
country: Peru
facility: Investigator Site 2
city: Lima
country: Peru
facility: Investigator Site 3
city: Lima
country: Peru
facility: Investigator Site 4
city: Cebu City
country: Philippines
facility: Investigator Site 1
city: Cebu City
country: Philippines
facility: Investigator Site 2
city: Lipa City
country: Philippines
facility: Investigator Site
city: Makati City
country: Philippines
facility: Investigator Site
city: Manila
country: Philippines
facility: Investigator Site
city: Quezon City
country: Philippines
facility: Investigator Site
city: Bydgoszcz
country: Poland
facility: Investigator Site
city: Katowice
country: Poland
facility: Investigator Site
city: Poznan
country: Poland
facility: Investigator Site 1
city: Poznan
country: Poland
facility: Investigator Site 2
city: Szczecin
country: Poland
facility: Investigator Site
city: Łódź
country: Poland
facility: Investigator Site 1
city: Łódź
country: Poland
facility: Investigator Site 2
city: Almada
country: Portugal
facility: Investigator Site
city: Amadora
country: Portugal
facility: Investigator Site
city: Lisboa
country: Portugal
facility: Investigator Site
city: Ponte de Lima
country: Portugal
facility: Investigator Site
city: Porto
country: Portugal
facility: Investigator Site
city: Kazan
country: Russian Federation
facility: Investigator Site
city: Kemerovo
country: Russian Federation
facility: Investigator Site
city: Orenburg
country: Russian Federation
facility: Investigator Site
city: Ryazan
country: Russian Federation
facility: Investigator Site
city: Saint-Petersburg
country: Russian Federation
facility: Investigator Site 1
city: Saint-Petersburg
country: Russian Federation
facility: Investigator Site 2
city: Smolensk
country: Russian Federation
facility: Investigator Site
city: Vladimir
country: Russian Federation
facility: Investigator Site
city: Voronezh
country: Russian Federation
facility: Investigator Site
city: Belgrade
country: Serbia
facility: Investigator Site 1
city: Belgrade
country: Serbia
facility: Investigator Site 2
city: Belgrade
country: Serbia
facility: Investigator Site 3
city: Belgrade
country: Serbia
facility: Investigator Site 4
city: Belgrade
country: Serbia
facility: Investigator Site 5
city: Niska Banja
country: Serbia
facility: Investigator Site
city: A Coruna
country: Spain
facility: Investigator Site
city: Barcelona
country: Spain
facility: Investigator Site 1
city: Barcelona
country: Spain
facility: Investigator Site 2
city: Barcelona
country: Spain
facility: Investigator Site 3
city: Bilbao
country: Spain
facility: Investigator Site
city: Madrid
country: Spain
facility: Investigator Site 1
city: Madrid
country: Spain
facility: Investigator Site 2
city: Sant Joan Despi
country: Spain
facility: Investigator Site
city: Kaohsiung
country: Taiwan
facility: Investigator Site
city: Taichung
country: Taiwan
facility: Investigator Site 1
city: Taichung
country: Taiwan
facility: Investigator Site 2
city: Taipei
country: Taiwan
facility: Investigator Site
city: Taoyuan
country: Taiwan
facility: Investigator Site
city: Ivano-Frankivs'k
country: Ukraine
facility: Investigator Site
city: Kharkiv
country: Ukraine
facility: Investigator Site
city: Kryvyi Rih
country: Ukraine
facility: Investigator Site
city: Kyiv
country: Ukraine
facility: Investigator Site 1
city: Kyiv
country: Ukraine
facility: Investigator Site 2
city: Kyiv
country: Ukraine
facility: Investigator Site 3
city: Lviv
country: Ukraine
facility: Investigator Site
city: Poltava
country: Ukraine
facility: Investigator Site 1
city: Poltava
country: Ukraine
facility: Investigator Site 2
city: Vinnytsia
country: Ukraine
facility: Investigator Site 1
city: Vinnytsia
country: Ukraine
facility: Investigator Site 2
Study officials:
affiliation: Ablynx NV
name: Medical Lead
role: STUDY_DIRECTOR
References:
citation: Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.