A Biomarker Study of Secukinumab in Rheumatoid Arthritis (RA) Patients

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01426789
• Other study ID #: CAIN457F2208
• Status: Completed
• Phase: Phase 2
• First received: August 12, 2011
• Last updated: August 6, 2015
• Start date: August 2011
• Est. completion date: February 2014

Study information

• Verified date: August 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Placebo
Matching placebo to secukinumab I.V.
• Secukinumab
In part 1 (blinded period), participants randomized to secukinumab received 10 mg/kg I.V.. Participants, enrolled in part 2 (open label), received secukinumab 300 mg subcutaneous.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Kortrijk
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Frankfurt am Main
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Herne
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Muenchen
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Nizhny Novgorod
Russian Federation	Novartis Investigative Site	Petrozavodsk
Russian Federation	Novartis Investigative Site	Smolensk	Russia
Russian Federation	Novartis Investigative Site	St.Petersburg
Russian Federation	Novartis Investigative Site	Tver
Russian Federation	Novartis Investigative Site	Yaroslavl
Russian Federation	Novartis Investigative Site	Yaroslavl
United Kingdom	Novartis Investigative Site	Belfast
United Kingdom	Novartis Investigative Site	Manchester
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Anahiem	California
United States	Novartis Investigative Site	Clearwater	Florida
United States	Novartis Investigative Site	Coral Gables	Florida
United States	Novartis Investigative Site	Fleming Island	Florida
United States	Novartis Investigative Site	Marietta	Georgia
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Pinellas Park	Florida
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	South Bend	Indiana
United States	Novartis Investigative Site	Springfield	Missouri
United States	Novartis Investigative Site	Statesville	North Carolina
United States	Novartis Investigative Site	Tuscon	Arizona
United States	Novartis Investigative Site	Venice	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	A participant was considered to be a responder according to the ACR20 criteria if the participant had at least 20% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR).	12 weeks	No
Primary	Change From Baseline in Disease Activity Score 28 (DAS28) in Association With the Presence or Absence of HLA-DRB1 04	The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the tender joint count(TJC) and swollen joint count (SJC) out of a total of 28 joints, the high-sensitivity C-reactive protein (hsCRP), and the subject's 'global assessment' of disease activity/general health (GH). The subject's global assessment/GH was indicated by a visual analogue scale of 100 mm where the participant marked a point on a 100 mm line between 0 and 100 (0 indicated very good and 100 indicated very bad). The following formula was used to calculate DAS28: DAS-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) = 0.36*ln(CRP+1) + 0.014*GH = 0.96. A DAS28-CRP score > 5.1 implies active disease, <3.2 implies controlled disease and <2.6 implied remission. A negative change from baseline indicates improvement.	baseline, 12 weeks	No
Secondary	Percentage of Participants Who Achieve ACR50 and ACR70 With the Presence/Absence of the HLA-DRB1*04 Allelic Group	A participant was considered to be a responder according to the ACR50 or ACR70 criteria if the participant had at least 50% or 70% improvement, respectively, in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR).	12 weeks	No
Secondary	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	The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the tender joint count(TJC) and swollen joint count (SJC) out of a total of 28 joints, the high-sensitivity C-reactive protein (hsCRP), and the subject's 'global assessment' of disease activity/general health (GH). The subject's global assessment/GH was indicated by a visual analogue scale of 100 mm where the participant marked a point on a 100 mm line between 0 and 100 (0 indicated very good and 100 indicated very bad). The following formula was used to calculate DAS28: DAS-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) = 0.36*ln(CRP+1) + 0.014*GH = 0.96. A DAS28-CRP score > 5.1 implies active disease, <3.2 implies controlled disease and <2.6 implied remission. A negative change from baseline indicates improvement.	baseline, 12 weeks	No