Efficacy of Secukinumab Compared to Adalimumab in Patients With Psoriatic Arthritis (EXCEED 1)

A Randomized, Double-blind, Active Control, Multicenter Study to Evaluate the Efficacy at Week 52 of Secukinumab Monotherapy Compared With Adalimumab Monotherapy in Patients With Active Psoriatic Arthritis

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).

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Biological: Secukinumab; Biological: Adalimumab

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.

• Study Type: Interventional
• Enrollment (Actual): 853
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Novartis Investigative Site
  • Queensland
    • Maroochydore, Queensland, Australia, 4558
      • Novartis Investigative Site
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Novartis Investigative Site
  • Victoria
    • Malvern East, Victoria, Australia, 3145
      • Novartis Investigative Site
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Novartis Investigative Site
  • Plovdiv, Bulgaria, 4002
    • Novartis Investigative Site
  • Plovdiv, Bulgaria, 4000
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1413
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1606
    • Novartis Investigative Site
• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 3M9
      • Novartis Investigative Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M1
      • Novartis Investigative Site
  • Quebec
    • Trois-Rivieres, Quebec, Canada, G8Z 1Y2
      • Novartis Investigative Site
• Czechia
  • Bruntal, Czechia, 792 01
    • Novartis Investigative Site
  • Praha 2, Czechia, 128 50
    • Novartis Investigative Site
  • Praha 5, Czechia, 150 06
    • Novartis Investigative Site
  • Uherske Hradiste, Czechia, 686 01
    • Novartis Investigative Site
  • Zlin, Czechia, 760 01
    • Novartis Investigative Site
• Denmark
  • Frederiksberg, Denmark, DK-2000
    • Novartis Investigative Site
• Estonia
  • Tallinn, Estonia, 13419
    • Novartis Investigative Site
  • Tallinn, Estonia, 10138
    • Novartis Investigative Site
  • Tartu, Estonia, 50406
    • Novartis Investigative Site
• Finland
  • Hyvinkaa, Finland, 05800
    • Novartis Investigative Site
  • Kuopio, Finland, 70100
    • Novartis Investigative Site
• France
  • Brive-la-Gaillarde, France, 19100
    • Novartis Investigative Site
  • Cahors, France, 46000
    • Novartis Investigative Site
  • Chambray les Tours, France, 37170
    • Novartis Investigative Site
  • Le Mans, France, 72037
    • Novartis Investigative Site
  • Orleans, France, 45100
    • Novartis Investigative Site
  • Paris, France, 75010
    • Novartis Investigative Site
  • Poitiers, France, 86021
    • Novartis Investigative Site
• Germany
  • Bad Doberan, Germany, 18209
    • Novartis Investigative Site
  • Berlin, Germany, 10117
    • Novartis Investigative Site
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Berlin, Germany, 14059
    • Novartis Investigative Site
  • Berlin, Germany, 12161
    • Novartis Investigative Site
  • Bochum, Germany, 44791
    • Novartis Investigative Site
  • Erlangen, Germany, 91056
    • Novartis Investigative Site
  • Hamburg, Germany, 22415
    • Novartis Investigative Site
  • Herne, Germany, 44649
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Magdeburg, Germany, 39110
    • Novartis Investigative Site
  • Osnabruck, Germany, 49074
    • Novartis Investigative Site
  • Schwerin, Germany, 19055
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 115 27
    • Novartis Investigative Site
  • Athens, Greece, 12462
    • Novartis Investigative Site
  • Thessaloniki, Greece, 54642
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1023
    • Novartis Investigative Site
  • Budapest, Hungary, 1062
    • Novartis Investigative Site
  • Budapest, Hungary, 1027
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Gyor, Hungary, 9023
    • Novartis Investigative Site
  • Kistarcsa, Hungary, 2143
    • Novartis Investigative Site
  • Veszprem, Hungary, 8200
    • Novartis Investigative Site
• Iceland
  • Reykjavik, Iceland, 108
    • Novartis Investigative Site
• India
  • New Delhi, India, 110029
    • Novartis Investigative Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400 053
      • Novartis Investigative Site
    • Nashik, Maharashtra, India, 422 101
      • Novartis Investigative Site
  • Telangana
    • Secunderabad, Telangana, India, 500003
      • Novartis Investigative Site
• Israel
  • Haifa, Israel, 3525408
    • Novartis Investigative Site
  • Haifa, Israel, 3339419
    • Novartis Investigative Site
  • Haifa, Israel, 343621
    • Novartis Investigative Site
  • Kfar Saba, Israel, 4428164
    • Novartis Investigative Site
  • Petach Tikva, Israel, 49100
    • Novartis Investigative Site
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • Bologna, Italy, 40138
    • Novartis Investigative Site
  • Pisa, Italy, 56126
    • Novartis Investigative Site
  • Torino, Italy, 10126
    • Novartis Investigative Site
  • GE
    • Arenzano, GE, Italy, 16011
      • Novartis Investigative Site
  • MI
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37126
      • Novartis Investigative Site
• Korea, Republic of
  • Seocho Gu
    • Seoul, Seocho Gu, Korea, Republic of, 06591
      • Novartis Investigative Site
• Latvia
  • Riga, Latvia, LV-1005
    • Novartis Investigative Site
  • Valmiera, Latvia, LV-4201
    • Novartis Investigative Site
• Lithuania
  • Klaipeda, Lithuania, LT-92288
    • Novartis Investigative Site
  • Siauliai, Lithuania, LT-76231
    • Novartis Investigative Site
  • LTU
    • Kaunas, LTU, Lithuania, LT 50161
      • Novartis Investigative Site
• Netherlands
  • Enschede, Netherlands, 7513 ER
    • Novartis Investigative Site
  • Sneek, Netherlands, 8601 ZK
    • Novartis Investigative Site
• Poland
  • Dopiewo, Poland, 62 069
    • Novartis Investigative Site
  • Szczecin, Poland, 71-252
    • Novartis Investigative Site
  • Warszawa, Poland, 02 637
    • Novartis Investigative Site
  • Warszawa, Poland, 04141
    • Novartis Investigative Site
• Portugal
  • Lisboa, Portugal, 1050-034
    • Novartis Investigative Site
  • Lisboa, Portugal, 1649-035
    • Novartis Investigative Site
  • Ponte de Lima, Portugal, 4990 041
    • Novartis Investigative Site
  • Porto, Portugal, 4200 319
    • Novartis Investigative Site
  • Porto, Portugal, 4099 001
    • Novartis Investigative Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620028
    • Novartis Investigative Site
  • Kemerovo, Russian Federation, 650029
    • Novartis Investigative Site
  • Kemerovo, Russian Federation, 650056
    • Novartis Investigative Site
  • Moscow, Russian Federation, 115522
    • Novartis Investigative Site
  • Moscow, Russian Federation, 119049
    • Novartis Investigative Site
  • Nizhny Novgorod, Russian Federation, 603018
    • Novartis Investigative Site
  • Petrozavodsk, Russian Federation, 185019
    • Novartis Investigative Site
  • Rostov on Don, Russian Federation, 344022
    • Novartis Investigative Site
  • Smolensk, Russian Federation, 214019
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150003
    • Novartis Investigative Site
• Slovakia
  • Bratislava, Slovakia, 81369
    • Novartis Investigative Site
  • Kosice, Slovakia, 04011
    • Novartis Investigative Site
  • Partizanske, Slovakia, 95801
    • Novartis Investigative Site
  • Topolcany, Slovakia, 95501
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08025
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28942
    • Novartis Investigative Site
  • Sevilla, Spain, 41014
    • Novartis Investigative Site
  • Valencia, Spain, 46026
    • Novartis Investigative Site
  • Andalucia
    • Cordoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
    • Malaga, Andalucia, Spain, 29009
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Novartis Investigative Site
    • L Hospitalet De Llobregat, Barcelona, Spain, 08907
      • Novartis Investigative Site
    • Sabadell, Barcelona, Spain, 08208
      • Novartis Investigative Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46017
      • Novartis Investigative Site
  • Extremadura
    • Merida, Extremadura, Spain, 06800
      • Novartis Investigative Site
  • Galicia
    • La Coruna, Galicia, Spain, 15006
      • Novartis Investigative Site
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
  • Pais Vasco
    • Bilbao, Pais Vasco, Spain, 48013
      • Novartis Investigative Site
  • Santa Cruz De Tenerife
    • La Laguna, Santa Cruz De Tenerife, Spain, 38320
      • Novartis Investigative Site
  • Vizcaya
    • Baracaldo, Vizcaya, Spain, 48903
      • Novartis Investigative Site
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Novartis Investigative Site
  • Glasgow, United Kingdom, G31 2ER
    • Novartis Investigative Site
  • Hull, United Kingdom, HU3 2JZ
    • Novartis Investigative Site
  • London, United Kingdom, SE1 9RT
    • Novartis Investigative Site
  • London, United Kingdom, NW3 2QG
    • Novartis Investigative Site
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Novartis Investigative Site
  • Plymouth, United Kingdom, PL6 8DH
    • Novartis Investigative Site
  • Solihull, United Kingdom, B91 2JL
    • Novartis Investigative Site
  • Wigan, United Kingdom, WN6 9EP
    • Novartis Investigative Site
  • Wolverhampton, United Kingdom, WV10 0QP
    • Novartis Investigative Site
  • Devon
    • Torquay, Devon, United Kingdom, TQ2 7AA
      • Novartis Investigative Site
  • London
    • Leytonstone, London, United Kingdom, E11 1NR
      • Novartis Investigative Site
  • Manchester
    • Salford, Manchester, United Kingdom, M6 8HD
      • Novartis Investigative Site
  • Staffordshire
    • Cannock, Staffordshire, United Kingdom, WS11 5XY
      • Novartis Investigative Site
    • Stoke on Trent, Staffordshire, United Kingdom, ST6 7AG
      • Novartis Investigative Site
• United States
  • California
    • Fountain Valley, California, United States, 92708
      • Novartis Investigative Site
    • Fullerton, California, United States, 92835
      • Novartis Investigative Site
    • La Mesa, California, United States, 91942
      • Novartis Investigative Site
    • Upland, California, United States, 91786
      • Novartis Investigative Site
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Novartis Investigative Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Novartis Investigative Site
    • Omaha, Nebraska, United States, 68114
      • Novartis Investigative Site
  • New York
    • Rochester, New York, United States, 14623
      • Novartis Investigative Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • Novartis Investigative Site
    • Duncansville, Pennsylvania, United States, 16635
      • Novartis Investigative Site
  • Texas
    • Arlington, Texas, United States, 76011
      • Novartis Investigative Site
    • Austin, Texas, United States, 78731
      • Novartis Investigative Site
    • Dallas, Texas, United States, 75231
      • Novartis Investigative Site
    • Mesquite, Texas, United States, 75150
      • Novartis Investigative Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Novartis Investigative Site
  • Washington
    • Seattle, Washington, United States, 98122
      • Novartis Investigative Site
    • Spokane, Washington, United States, 99204
      • Novartis Investigative Site
  • Wisconsin
    • Glendale, Wisconsin, United States, 53217
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Secukinumab 300 mg s.c.; Secukinumab 300 mg administered at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 48.	Biological: Secukinumab; Eligible subjects are randomized to one of two treatment arms in a 1:1 ratio; Other Names: AIN457
ACTIVE_COMPARATOR: Adalimumab 40 mg s.c.; Adalimumab 40 mg administered at Baseline followed by dosing every 2 weeks until Week 50.	Biological: Adalimumab; Eligible subjects are randomized to one of two treatment arms in a 1:1 ratio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at 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: achieving American College of Rheumatology 20 (ACR20) response; no permanent study treatment (secukinumab or adalimumab) discontinuation before or at Week 50 (the last dosing visit); 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)	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI)-90 Response at 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.	Week 52
Percentage of Participants Who Achieved an American College of Rheumatology 50% (ACR50) Response at 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: achieving American College of Rheumatology 50 (ACR50) response; no permanent study treatment (secukinumab or adalimumab) discontinuation before or at Week 52; 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)	Week 52
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI Score) at 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.	Baseline, Week 52
Percentage of Participants Who Achieved Resolution of Enthesitis at 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.	Week 52

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• McInnes IB, Behrens F, Mease PJ, Kavanaugh A, Ritchlin C, Nash P, Masmitja JG, Goupille P, Korotaeva T, Gottlieb AB, Martin R, Ding K, Pellet P, Mpofu S, Pricop L; EXCEED Study Group. Secukinumab versus adalimumab for treatment of active psoriatic arthritis (EXCEED): a double-blind, parallel-group, randomised, active-controlled, phase 3b trial. Lancet. 2020 May 9;395(10235):1496-1505. doi: 10.1016/S0140-6736(20)30564-X. Erratum In: Lancet. 2020 May 30;395(10238):1694.

Helpful Links

• Secukinumab versus adalimumab for treatment of active psoriatic arthritis (EXCEED): a double-blind, parallel-group, randomised, active-controlled, phase 3b trial

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 3, 2017
• Primary Completion (ACTUAL): December 30, 2019
• Study Completion (ACTUAL): December 30, 2019

Study Registration Dates

• First Submitted: April 1, 2016
• First Submitted That Met QC Criteria: April 19, 2016
• First Posted (ESTIMATE): April 20, 2016

Study Record Updates

• Last Update Posted (ACTUAL): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Psoriatic Arthritis; monoclonal antibody; adalimumab; secukinumab; CASPAR
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: CAIN457F2366; 2015-004477-32 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No