Efficacy of Secukinumab Compared to Adalimumab in Patients With Psoriatic Arthritis

Phase 3

Completed

Conditions: Psoriatic Arthritis

Interventions: Biological: Secukinumab
Biological: Adalimumab

Registration Number: NCT02745080

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This was a randomized, double-blind, active controlled, multicenter, parallel-group study evaluating secukinumab monotherapy and adalimumab monotherapy in approximately 850 patients with active psoriatic arthritis (PsA) who are naïve to biologic therapy and are intolerant or having inadequate response to conventional disease modifying anti-rheumatic drugs (also known as non-biologic DMARDs).

Detailed Description: The total maximum study duration, including the screening period was up to 76 weeks.

At Baseline, patients whose eligibility was confirmed were randomized to 1 of 2 groups (1:1): Group 1 (secukinumab 300 mg) or Group 2 (adalimumab 40 mg).

In order to maintain the blind, both groups received 1 or 2 placebo s.c. injections to keep consistency in the number of injections at each dosing visit. Secukinumab (300 mg) was available in 2 x 1.0 mL pre-filled syringes (PFS) and adalimumab was available in 1 x 0.4 mL PFS. Placebo (1.0 and 0.5 mL PFS) was also available.

Secukinumab 300 mg s.c injection (2 x 1 mL PFS) was administered at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks to Week 48.

Adalimumab 40 mg (1 x 0.4 mL PFS) was administered at Baseline followed by dosing every 2 weeks until Week 50.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 853

Inclusion Criteria

Diagnosis of PsA classified by CASPAR
Rheumatoid factor and anti-CCP antibodies negative
Diagnosis of active plaque psoriasis, with at least one psoriatic plaque of >= 2cm diameter or nail changes consistent with psoriasis or documented history of plaque psoriasis
Inadequate control of symptoms with NSAIDs
Inadequate control of symptoms with a conventional DMARD.

Key

Exclusion Criteria

Pregnant or nursing women
Evidence of ongoing infectious or malignant process
Previous exposure to any biologic drug for Psoriatic Arthritis or Psoriasis
Subjects taking high potency opioid analgesics
Ongoing use of prohibited psoriasis treatments/medications
Previous treatment with any cell-depleting therapies including but not limited to anti-CD20 investigational agents.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Secukinumab 300 mg s.c.	Secukinumab	Secukinumab 300 mg administered at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 48.
Adalimumab 40 mg s.c.	Adalimumab	Adalimumab 40 mg administered at Baseline followed by dosing every 2 weeks until Week 50.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Week 52	Week 52	Clinical response, failure to permanently discontinue study medication prematurely, and lack of need for rescue medication was required for a patient to achieve treatment success. The primary endpoint is the proportion of patients with monotherapy ACR20 response at Week 52 where monotherapy ACR20 response is defined as meeting the following 3 conditions: 1. achieving American College of Rheumatology 20 (ACR20) response 2. no permanent study treatment (secukinumab or adalimumab) discontinuation before or at Week 50 (the last dosing visit) 3. no use of conventional disease modifying anti-rheumatic drugs (also known as non-biologic DMARDs) cDMARDs (including Methotrexate (MTX)) after Week 36 (regardless of the starting time of taking cDMARDs)

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI)-90 Response at Week 52	Week 52	The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents participants who achieved at least a 90 percent improvement from baseline in the PASI score.
Percentage of Participants Who Achieved an American College of Rheumatology 50% (ACR50) Response at Week 52	Week 52	Clinical response, failure to permanently discontinue study medication prematurely, and lack of need for rescue medication was required for a patient to achieve treatment success. The secondary endpoint is the proportion of patients with monotherapy ACR50 response at Week 52 where monotherapy ACR50 response is defined as meeting the following 3 conditions: 1. achieving American College of Rheumatology 50 (ACR50) response 2. no permanent study treatment (secukinumab or adalimumab) discontinuation before or at Week 52 3. no use of conventional disease modifying anti-rheumatic drugs (also known as non-biologic DMARDs) cDMARDs (including Methotrexate (MTX)) after Week 36 (regardless of the starting time of taking cDMARDs)
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI Score) at Week 52	Baseline, Week 52	The HAQ-DI assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, "are you able to..." perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement.
Percentage of Participants Who Achieved Resolution of Enthesitis at Week 52	Week 52	Enthesitis refers to inflammation of entheses, the site where ligaments or tendons insert into the bones. Resolution was defined as the absence of recorded enthesitis; conducted by the study assessor.