Clinical trial NCT02287922: A Phase IIb Study for ALX-0061 Monotherapy in Subjects With Rheumatoid Arthritis
Official title: A Phase IIb Multicenter, Randomized, Double-blind Study of ALX-0061 Administered Subcutaneously as Monotherapy, in Subjects With Moderate to Severe Rheumatoid Arthritis Who Are Intolerant to Methotrexate or for Whom Continued Methotrexate Treatment is Inappropriate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Ablynx, a Sanofi company
Sponsor class: INDUSTRY
First posted: 2014-11-11
Enrollment: 251
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 primary objective of this study is:

- To assess the efficacy and safety of dose regimens of ALX-0061 monotherapy administered subcutaneously (s.c.) to subjects with active rheumatoid arthritis (RA).

The secondary objectives of this study are:

* To assess the effects of ALX-0061 on quality of life, the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ALX-0061 and to explore potential dose regimens for ALX-0061 monotherapy, based on safety and efficacy, for further clinical development.
* To obtain parallel descriptive information concerning the efficacy and safety of tocilizumab (TCZ) s.c. in the same clinical trial RA population.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of RA (according to the 2010 EULAR/American College of Rheumatology (ACR) classification criteria) for at least 6 months prior to screening, and ACR functional class I-III.
* Received previous or current treatment with methotrexate (MTX), and is considered intolerant to MTX, or for whom continued treatment with MTX is inappropriate or has contraindications for MTX use.
* Subjects must not have received MTX for at least 4 weeks before first administration of the study drug.
* Have active RA with at least 6 swollen and 6 tender joints(66/68 joint count) at the time of screening and baseline
* Others as defined in the protocol

Exclusion Criteria:

* Have been treated with DMARDs (Disease Modifying Antirheumatic Drugs)/systemic immunosuppressive drugs during the 4 weeks, or 12 weeks for hydroxychloroquine, chloroquine, or leflunomide (except when an adequate wash-out procedure for leflunomide was completed), prior to first administration of study drug.
* Have received approved or investigational biological or targeted synthetic DMARD therapies for RA (including tumor necrosis factor alpha-inhibitors, abatacept, rituximab, or Janus kinase \[JAK\]-inhibitors) 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 (including JAK inhibitors), 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 With American College of Rheumatology 20 (ACR20) at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12
timeFrame: Week 12
measure: Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score Using 28 Joint Counts (DAS28) Using C-reactive Protein (CRP) at Week 12
timeFrame: Week 12
measure: Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Week 12
timeFrame: Week 12
measure: Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Week 12
timeFrame: Week 12
measure: Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Week 12
timeFrame: Week 12
measure: Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Week 12
timeFrame: Week 12
measure: Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Week 12
timeFrame: Week 12
measure: Number and Percentage of Subjects in Remission Using SDAI at Week 12
timeFrame: Week 12
measure: Number and Percentage of Subjects in Remission Using CDAI at Week 12
timeFrame: Week 12
measure: Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Week 12
timeFrame: Week 12
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12
timeFrame: From baseline until Week 12
measure: Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12
timeFrame: From baseline until week 12
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Week 12
timeFrame: From baseline until Week 12
measure: Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R)
timeFrame: From baseline until Week 12
measure: Pharmacokinetics: ALX-0061 Concentration in Serum at Week 12
timeFrame: From baseline until Week 12
measure: Number and Percentage of Subjects With Development of a Treatment-emergent Antidrug Antibody Response
timeFrame: From first study drug intake up to and including follow-up (FU), i.e., maximum of 22 weeks (10 weeks of treatment + 12 weeks of FU)
measure: Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity
timeFrame: From baseline until Week 12
measure: Number of Treatment-emergent Adverse Event by Severity
timeFrame: From baseline until Week 12
measure: Number and Percentage of Subjects With a Treatment-related Treatment-emergent Adverse Event
timeFrame: From baseline until Week 12
measure: Number of Treatment-related Treatment-emergent Adverse Event
timeFrame: From baseline until Week 12
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 site
state: Florida
city: Homestead
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: Worcester
country: United States
facility: Investigator Site
state: Massachusetts
city: Albuquerque
country: United States
facility: Investigator Site
state: New Mexico
city: New York
country: United States
facility: Investigator Site
state: New York
city: Charleston
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: Ghent
country: Belgium
facility: Investigator Site
city: Liège
country: Belgium
facility: Investigator Site
city: Burgas
country: Bulgaria
facility: Investigator Site
city: Pleven
country: Bulgaria
facility: Investigator Site
city: Plovdiv
country: Bulgaria
facility: Investigator Site 1
city: Plovdiv
country: Bulgaria
facility: Investigator Site 2
city: Ruse
country: Bulgaria
facility: Investigator Site 1
city: Ruse
country: Bulgaria
facility: Investigator Site 2
city: Sofia
country: Bulgaria
facility: Investigator Site
city: Brno
country: Czechia
facility: Investigator Site
city: Olomouc
country: Czechia
facility: Investigator Site
city: Ostrava
country: Czechia
facility: Investigator Site
city: Prague
country: Czechia
facility: Investigator Site 1
city: Prague
country: Czechia
facility: Investigator Site 2
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: Berlin
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: Budapest
country: Hungary
facility: Investigator Site
city: Esztergom
country: Hungary
facility: Investigator Site
city: Gyula
country: Hungary
facility: Investigator site
city: Szikszo
country: Hungary
facility: Investigator Site
city: Szombathely
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: Mexico City 1
country: Mexico
facility: Investigator Site
city: Mexico City
country: Mexico
facility: Investigator Site 1
city: Mexico City
country: Mexico
facility: Investigator Site 2
city: Monterrey
country: Mexico
facility: Investigator Site 1
city: Monterrey
country: Mexico
facility: Investigator Site 2
city: Chisinau
country: Moldova, Republic of
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 2
city: Elblag
country: Poland
facility: Investigator Site
city: Gdynia
country: Poland
facility: Investigator Site
city: Grodzisk Mazowiecki
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: Bucharest
country: Romania
facility: Investigator Site
city: Oradea
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: Cordoba
country: Spain
facility: Investigator Site
city: Madrid
country: Spain
facility: Investigator Site
city: Santander
country: Spain
facility: Investigator Site
city: Santander
country: Spain
facility: Investigator Site 2
city: Santiago de Compostela
country: Spain
facility: Investigator Site 1
city: Santiago de Compostela
country: Spain
facility: Investigator Site 2
Study officials:
affiliation: Ablynx, a Sanofi company
name: Medical Monitor, MD
role: STUDY_DIRECTOR
References: