Clinical trial NCT02309359: A Dose-Range Finding Study for ALX-0061 Combination Therapy in Subjects With Rheumatoid Arthritis
Official title: A Phase IIb Multicenter, Randomized, Double-blind, Placebo-Controlled Dose-Range Finding Study of ALX-0061 Administered Subcutaneously in Combination With Methotrexate, in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Ablynx, a Sanofi company
Sponsor class: INDUSTRY
First posted: 2014-12-05
Enrollment: 345
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy and safety of dose regimens of ALX-0061 administered subcutaneously (s.c.) in combination with methotrexate (MTX) to subjects with active rheumatoid arthritis (RA) despite MTX therapy, compared with placebo.

To assess the effects of ALX-0061 on quality of life, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ALX-0061, and to define the optimal dose regimen for ALX-0061, based on safety and efficacy, for further clinical development.

Detailed description: Subjects who completed the 24-week assessment period and achieved at least 20% improvement in swollen joint count (SJC) and/or tender joint count (TJC) at Week 24 of study ALX0061-C201 were invited to participate in an open-label extension (OLE) study ALX0061-C203 (NCT02518620), if the study was approved in their country and selection criteria were met.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of RA for at least 6 months prior to screening, and American College of Rheumatology (ACR) functional class I-III
* Subjects treated with and tolerating MTX
* Active RA
* Others as defined in the protocol

Exclusion Criteria:

* Have been treated with disease-modifying antirheumatic drugs (DMARDs)/systemic immunosuppressives other than MTX.
* Have received approved or investigational biological or targeted synthetic DMARD therapies for RA less than 6 months prior to screening.
* Have a history of toxicity, non-tolerance, primary non-response or inadequate response to a biological therapy, or targeted synthetic DMARDs, for RA.
* Have received prior therapy blocking the interleukin-6 (IL-6) pathway, at any time.
* Others as defined in the protocol

Primary outcomes:
measure: Number and Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Response at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Number and Percentage of Subjects With ACR20 Response at Week 24
timeFrame: 24 weeks
measure: Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24
timeFrame: 24 weeks
measure: Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24
timeFrame: 24 weeks
measure: Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24
timeFrame: 24 weeks
measure: Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24
timeFrame: 24 weeks
measure: Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24
timeFrame: 24 weeks
measure: Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24
timeFrame: 24 weeks
measure: Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24
timeFrame: 24 weeks
measure: Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24
timeFrame: 24 weeks
measure: Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24
timeFrame: 24 weeks
measure: Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24
timeFrame: 24 weeks
measure: Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24
timeFrame: 24 weeks
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24
timeFrame: from baseline till Week 24
measure: Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24
timeFrame: from baseline till Week 24
measure: Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24
timeFrame: from baseline till Week 24
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24
timeFrame: from baseline till Week 24
measure: Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24
timeFrame: at Week 12 and Week 24 visits
measure: Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24
timeFrame: from baseline till Week 24
measure: Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response
timeFrame: from baseline till follow-up (FU) (i.e., 12 weeks after last study drug dosing at Week 22 or after early treatment discontinuation)
measure: Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity
timeFrame: From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit
measure: Number of Treatment-emergent Adverse Events by Severity
timeFrame: From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit
measure: Number and Percentage of Subjects With Treatment-related Treatment-emergent Adverse Events
timeFrame: From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit
measure: Number of Treatment-related Treatment-emergent Adverse Events
timeFrame: From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigator Site
state: Alabama
city: Hemet
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: Los Angeles
country: United States
facility: Investigator site
state: California
city: Ventura
country: United States
facility: Investigator Site
state: California
city: Hialeah
country: United States
facility: Investigator Sites
state: Florida
city: Homestead
country: United States
facility: Investigator Site
state: Florida
city: Miami Lakes
country: United States
facility: Investigator Site
state: Florida
city: Miami
country: United States
facility: Investigator Site
state: Florida
city: Orlando
country: United States
facility: Investigator Site
state: Florida
city: Stockbridge
country: United States
facility: Investigator Site
state: Georgia
city: Overland Park
country: United States
facility: Investigator Site
state: Kansas
city: Monroe
country: United States
facility: Investigator Site
state: Louisiana
city: Worcester
country: United States
facility: Investigator Site
state: Massachusetts
city: Albuquerque
country: United States
facility: Investigator Site
state: New Mexico
city: Brooklyn
country: United States
facility: Investigator Site
state: New York
city: New York
country: United States
facility: Investigator Site
state: New York
city: Charleston
country: United States
facility: Investigator Sie
state: South Carolina
city: Myrtle Beach
country: United States
facility: Investigator Site
state: South Carolina
city: Memphis
country: United States
facility: Investigator Site
state: Tennessee
city: Mesquite
country: United States
facility: Investigator Site
state: Texas
city: Brussels
country: Belgium
facility: Investigator Site
city: Brussels
country: Belgium
facility: Investigator Site
city: Ghent
country: Belgium
facility: Investigator Site
city: Liège
country: Belgium
facility: Investigator Site
city: Pleven
country: Bulgaria
facility: Investigator Site
city: Plovdiv
country: Bulgaria
facility: Investigator Site
city: Ruse
country: Bulgaria
facility: Investigator Site 1
city: Ruse
country: Bulgaria
facility: Investigator Site 2
city: Sofia
country: Bulgaria
facility: Investigator Site
city: Sofia
country: Bulgaria
facility: Investigator Site
city: Varna
country: Bulgaria
facility: Investigator Site
city: Brno
country: Czechia
facility: Investigator Site
city: Olomouc
country: Czechia
facility: Investigator Site
city: Prague
country: Czechia
facility: Investigator Site
city: Prague
country: Czechia
facility: Investigator Site
city: Zlin
country: Czechia
facility: Investigator Site
city: Tbilisi
country: Georgia
facility: Investigator Site
city: Tbilisi
country: Georgia
facility: Investigator Site 1
city: Tbilisi
country: Georgia
facility: Investigator Site 2
city: Tbilisi
country: Georgia
facility: Investigator Site
city: Tbilisi
country: Georgia
facility: Investigator Site
city: Bad Nauheim
country: Germany
facility: Investigator Site
city: Berlin
country: Germany
facility: Investigator Site
city: Berlin
country: Germany
facility: Investigator Site
city: Cologne
country: Germany
facility: Investigator Site
city: Frankfurt
country: Germany
facility: Investigator Site
city: Hamburg
country: Germany
facility: Investigator Site
city: Baja
country: Hungary
facility: Investigator Site
city: Balatonfüred
country: Hungary
facility: Investigator Site
city: Budapest
country: Hungary
facility: Investigator Site
city: Békéscsaba
country: Hungary
facility: Investigator Site
city: Gyula
country: Hungary
facility: Investigator Site
city: Szikszó
country: Hungary
facility: Investigator Site
city: Székesfehérvar
country: Hungary
facility: Investigator Site
city: Veszprém
country: Hungary
facility: Investigator Site
city: Culiacan
country: Mexico
facility: Investigator Site
city: Leon
country: Mexico
facility: Investigator Site
city: Merida
country: Mexico
facility: Investigator Site
city: Mexico City
country: Mexico
facility: Investigator Site 1
city: Mexico City
country: Mexico
facility: Investigator Site 2
city: Monclova
country: Mexico
facility: Investigator Site
city: Monterey
country: Mexico
facility: Investigator Site
city: Monterey
country: Mexico
facility: Investigator Site
city: Chisinau
country: Moldova, Republic of
facility: Investigator Site
city: Skopje
country: North Macedonia
facility: Investigator Site 1
city: Skopje
country: North Macedonia
facility: Investigator Site 2
city: Bydgoszcz
country: Poland
facility: Investigator Site
city: Elblag
country: Poland
facility: Investigator Site
city: Elblag
country: Poland
facility: Investigator Site
city: Gdynia
country: Poland
facility: Investigator Site
city: Grodzisk Mazowiecki
country: Poland
facility: Investigator Site
city: Katowice
country: Poland
facility: Investigator Site
city: Lublin
country: Poland
facility: Investigator Site
city: Poznan
country: Poland
facility: Investigator Site
city: Sochaczew
country: Poland
facility: Investigator Site
city: Torun
country: Poland
facility: Investigator Site
city: Warszawa
country: Poland
facility: Investigator Site
city: Braila
country: Romania
facility: Investigator Site
city: Bucharest
country: Romania
facility: Investigator Site
city: Bucharest
country: Romania
facility: Investigator Site
city: Oradea
country: Romania
facility: Investigator Site
city: Targu Mures
country: Romania
facility: Investigator Site
city: Timisoara
country: Romania
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: Niska Banja
country: Serbia
facility: Investigator Site
city: Novi Sad
country: Serbia
facility: Investigator Site
city: Madrid
country: Spain
facility: Investigator Site
city: Madrid
country: Spain
facility: Investigator Site
city: Salamanca
country: Spain
facility: Investigator Site
city: Santiago de Compostela
country: Spain
facility: Investigator Site
Study officials:
affiliation: Ablynx, a Sanofi company
name: Ablynx Clinical Department
role: STUDY_DIRECTOR
References: