Clinical trial NCT01426789: A Biomarker Study of Secukinumab in Rheumatoid Arthritis (RA) Patients
Official title: A Multicenter, 12 Week, Randomized, Double-blind, Placebo-controlled Biomarker Study of Secukinumab (AIN457) in Rheumatoid Arthritis Patients Followed by an Open Label Extension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
IgG1K monoclonal antibody
Interleukin-17A neutralizing
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-08-31
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to confirm if patients with a specific biomarker might have a better response to secukinumab treatment. To meet this purpose, exploratory biomarker studies will be done. The goals of these exploratory studies are to (1) find biomarkers that will identify persons with rheumatoid arthritis who will have the best possible response to secukinumab and (2) to identify persons who will have fewer side effects in order to maximize their benefit from secukinumab.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of rheumatoid arthritis
* Patients must be either DMARD naive or have failed at least one DMARD agent (e.g. MTX, leflunamide or sulfasalazine)
* Patients are allowed up to 3 DMARDs at study entry (e.g. MTX, sulfasalazine or hydroxychloroquine) as long as their dose was stable for 4 weeks prior to initiating study treatment
* Disease activity at screening defined by ≥6 out of 28 tender joints and ≥6 out of 28 swollen joints and hsCRP \>10mg/L

Exclusion Criteria:

* Patients with severe rheumatoid arthritis (functional status class IV according to the ACR 1991 revised criteria)
* Previous exposure to secukinumab or any other biologic, including TNF inhibitors.
* Use of high potency opioid analgesics
* Pregnant or nursing (lactating) women
* Use of any investigational drug other than RA therapy and/or devices at the time of randomization or within 30 days or 5 half-lives of randomization, whichever is longer.

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20 ) in Association With the Presence or Absence of the HLA-DRB1 *4 Allelic Group
timeFrame: 12 weeks
measure: Change From Baseline in Disease Activity Score 28 (DAS28) in Association With the Presence or Absence of HLA-DRB1 04
timeFrame: baseline, 12 weeks
Secondary outcomes:
measure: Percentage of Participants Who Achieve ACR50 and ACR70 With the Presence/Absence of the HLA-DRB1*04 Allelic Group
timeFrame: 12 weeks
measure: Change From Baseline in DAS28 in Association With the Presence or Absence of HLA-DRB1 *SE (Positive), HLA-DRB1 *401 (Carrier) and HLA-DRB1 Position 11 V/L and in Association With Other Biomarkers
timeFrame: baseline, 12 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Tuscon
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Anahiem
country: United States
facility: Novartis Investigative Site
state: California
city: Clearwater
country: United States
facility: Novartis Investigative Site
state: Florida
city: Coral Gables
country: United States
facility: Novartis Investigative Site
state: Florida
city: Fleming Island
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Pinellas Park
country: United States
facility: Novartis Investigative Site
state: Florida
city: Venice
country: United States
facility: Novartis Investigative Site
state: Florida
city: Marietta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: South Bend
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Springfield
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Albuquerque
country: United States
facility: Novartis Investigative Site
state: New Mexico
city: Statesville
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Kortrijk
country: Belgium
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Herne
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Smolensk
country: Russian Federation
facility: Novartis Investigative Site
state: Russia
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Nizhny Novgorod
country: Russian Federation
facility: Novartis Investigative Site
city: Petrozavodsk
country: Russian Federation
facility: Novartis Investigative Site
city: St.Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Tver
country: Russian Federation
facility: Novartis Investigative Site
city: Yaroslavl
country: Russian Federation
facility: Novartis Investigative Site
city: Yaroslavl
country: Russian Federation
facility: Novartis Investigative Site
city: Belfast
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Burmester GR, Durez P, Shestakova G, Genovese MC, Schulze-Koops H, Li Y, Wang YA, Lewitzky S, Koroleva I, Berneis AA, Lee DM, Hueber W. Association of HLA-DRB1 alleles with clinical responses to the anti-interleukin-17A monoclonal antibody secukinumab in active rheumatoid arthritis. Rheumatology (Oxford). 2016 Jan;55(1):49-55. doi: 10.1093/rheumatology/kev258. Epub 2015 Aug 12.