Study to Demonstrate the Efficacy, Safety and Tolerability of Intravenous Secukinumab up to 52 Weeks in Subjects With Active Psoriatic Arthritis (INVIGORATE 2)

A Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase III Multicenter Study of Intravenous Secukinumab to Compare Efficacy at 16 Weeks With Placebo and to Assess Safety and Tolerability up to 52 Weeks in Subjects With Active Psoriatic Arthritis

The purpose of this study was to provide up to 52 weeks of efficacy, safety and tolerability data to support registration of intravenous (i.v.) secukinumab (Initial dose of 6 mg/kg at Baseline (BSL) followed thereafter with 3 mg/kg administered every four weeks) in patients with active psoriatic arthritis (PsA) despite current or previous Non-steroidal anti-inflammatory drugs (NSAIDs), Disease-modifying antirheumatic drugs (DMARDs) and/or anti-tumor necrosis factor (TNF) therapy.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Drug: AIN457 6 mg/kg i.v.; Drug: AIN457 3 mg/kg; Drug: Placebo

Detailed Description

This multicenter study used a randomized, double-blind, placebo-controlled, parallel-group design. A screening (SCR) period running up to 10 weeks before randomization was used to assess subject eligibility followed by a treatment period of 52 weeks.

At baseline, 381 patients with active psoriatic arthritis were randomized to one of the two treatment groups in a 1:1 randomization:

Group 1: Approximately 190 patients with active psoriatic arthritis; These patients received secukinumab 6 mg/kg i.v. at BSL, followed by the administration of secukinumab 3 mg/kg i.v. every four weeks starting at Week 4.

Group 2: Approximately 190 patients with active psoriatic arthritis; These patients received i.v. placebo at BSL and at Weeks 4, 8, and 12, followed by the administration of secukinumab 3 mg/kg i.v. every four weeks starting at Week 16.

Study consisted of 4 periods: a screening period (up to 10 weeks), treatment period 1 (total duration of 16 weeks) and treatment period 2 (total duration of 36 weeks) followed by a safety follow up period of 8 weeks after the end of treatment visit (i.e., Week 52).

Primary endpoint analysis will be performed with Week 16 data (last patient completing Treatment period 1 (Week 16). Long-term efficacy and safety assessments will be performed up to Week 52.

• Study Type: Interventional
• Enrollment (Actual): 381
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • BA
    • Salvador, BA, Brazil, 40150 150
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 04266 010
      • Novartis Investigative Site
• Bulgaria
  • Burgas, Bulgaria, 8000
    • Novartis Investigative Site
  • Plovdiv, Bulgaria, 4002
    • Novartis Investigative Site
  • Plovdiv, Bulgaria, 4000
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1413
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1431
    • Novartis Investigative Site
• Colombia
  • Bogota, Colombia, 110221
    • Novartis Investigative Site
  • Cundinamarca, Colombia, 111121
    • Novartis Investigative Site
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 080002
      • Novartis Investigative Site
  • Santander
    • Bucaramanga, Santander, Colombia, 0001
      • Novartis Investigative Site
• Czechia
  • Prague 2, Czechia, 128 50
    • Novartis Investigative Site
  • Praha 4, Czechia, 140 59
    • Novartis Investigative Site
  • Praha 5, Czechia, 150 06
    • Novartis Investigative Site
  • Uherske Hradiste, Czechia, 686 01
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 12462
    • Novartis Investigative Site
  • Thessaloniki, Greece, 54622
    • Novartis Investigative Site
• Guatemala
  • Guatemala, Guatemala, 01010
    • Novartis Investigative Site
  • Guatemala, Guatemala, 01001
    • Novartis Investigative Site
  • Guatemala City, Guatemala, 01010
    • Novartis Investigative Site
• India
  • New Delhi, India, 110029
    • Novartis Investigative Site
  • Gujarat
    • Surat, Gujarat, India, 395009
      • Novartis Investigative Site
  • Karnataka
    • Bangalore, Karnataka, India, 560 079
      • Novartis Investigative Site
  • Maharashtra
    • Nashik, Maharashtra, India, 422 101
      • Novartis Investigative Site
• Malaysia
  • Selangor Darul Ehsan, Malaysia, 68100
    • Novartis Investigative Site
  • Negeri Sembilan
    • Seremban, Negeri Sembilan, Malaysia, 70300
      • Novartis Investigative Site
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Novartis Investigative Site
• Philippines
  • Manila, Philippines, 1008
    • Novartis Investigative Site
  • Quezon City, Philippines, 1102
    • Novartis Investigative Site
  • Batangas
    • Lipa City, Batangas, Philippines, 4217
      • Novartis Investigative Site
  • Cavite
    • Dasmarinas, Cavite, Philippines, 4114
      • Novartis Investigative Site
• Poland
  • Karwiany, Poland, 52-200
    • Novartis Investigative Site
  • Krakow, Poland, 30 002
    • Novartis Investigative Site
  • Sochaczew, Poland, 96-500
    • Novartis Investigative Site
  • Warszawa, Poland, 02-962
    • Novartis Investigative Site
  • Malopolskie
    • Krakow, Malopolskie, Poland, 30-510
      • Novartis Investigative Site
• Russian Federation
  • Kemerovo, Russian Federation, 650029
    • Novartis Investigative Site
  • Nizhny Novgorod, Russian Federation, 603018
    • Novartis Investigative Site
  • Rostov On Don, Russian Federation, 344022
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 197022
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 190068
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150003
    • Novartis Investigative Site
  • Yekaterinburg, Russian Federation, 620109
    • Novartis Investigative Site
• South Africa
  • Stellenbosch, South Africa, 7600
    • Novartis Investigative Site
  • Western Cape
    • Panorama, Western Cape, South Africa, 7500
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
  • Bangkok
    • Bangkoknoi, Bangkok, Thailand, 10700
      • Novartis Investigative Site
  • Hat Yai
    • Songkhla, Hat Yai, Thailand, 90110
      • Novartis Investigative Site
  • THA
    • Khon Kaen, THA, Thailand, 40002
      • Novartis Investigative Site
• Turkey
  • Gorukle
    • Bursa, Gorukle, Turkey, 16059
      • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Novartis Investigative Site
  • 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
    • Santa Monica, California, United States, 90404
      • Novartis Investigative Site
    • Upland, California, United States, 91786
      • Novartis Investigative Site
    • Van Nuys, California, United States, 91405
      • Novartis Investigative Site
    • West Hills, California, United States, 91307
      • Novartis Investigative Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Novartis Investigative Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Novartis Investigative Site
    • Miami, Florida, United States, 33032
      • Novartis Investigative Site
    • Ocoee, Florida, United States, 34761
      • Novartis Investigative Site
    • Plantation, Florida, United States, 33324
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33624
      • Novartis Investigative Site
    • Winter Park, Florida, United States, 32789
      • Novartis Investigative Site
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • 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
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Novartis Investigative Site
  • New York
    • Rochester, New York, United States, 14642
      • Novartis Investigative Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Novartis Investigative Site
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Novartis Investigative Site
    • Tulsa, Oklahoma, United States, 74136
      • Novartis Investigative Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Novartis Investigative Site
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Novartis Investigative Site
  • Texas
    • Austin, Texas, United States, 78731
      • Novartis Investigative Site
    • Mesquite, Texas, United States, 75150
      • Novartis Investigative Site
  • Virginia
    • Newport News, Virginia, United States, 23608
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Patients eligible for inclusion in this study had to fulfill all of the following criteria:

• Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months with moderate to severe PsA who must have at Baseline ≥3 tender joints out of 78 and ≥3 swollen out of 76 (dactylitis of a digit counts as one joint each)
• Rheumatoid factor and anti-CCP antibodies negative at screening
• Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or documented history of plaque psoriasis
• Subjects with PsA should have taken NSAIDs for at least 4 weeks prior to randomization with inadequate control of symptoms or at least one dose if stopped due to intolerance to NSAIDs
• Subjects taking corticosteroids must be on a stable dose of ≤10 mg/day prednisone or equivalent for at least 2 weeks before randomization and should remain on a stable dose up to Week 16
• Subjects taking MTX (≤ 25 mg/week) are allowed to continue their medication if the dose is stable for at least 4 weeks before randomization and should remain on a stable dose up to Week 52.

Patients fulfilling any of the following criteria are not eligible for inclusion in this study:

• Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process, obtained within 3 months prior to screening and evaluated by a qualified physician
• Subjects taking high potency opioid analgesics (e.g. methadone, hydromorphone, morphine)
• Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor
• Ongoing use of prohibited psoriasis treatments / medications (e.g., topical corticosteroids, UV therapy) at randomization. The following wash-out periods need to be observed:
• Oral or topical retinoids- 4 weeks
• Photochemotherapy (e.g. PUVA)- 4 weeks
• Phototherapy (UVA or UVB)- 2 weeks
• Topical skin treatments (except in face, eyes, scalp and genital area during screening, only corticosteroids with mild to moderate potency)- 2 weeks
• Any intramuscular or intravenous corticosteroid treatment within 4 weeks before randomization.
• Any therapy by intra-articular injections (e.g. corticosteroid) within 4 weeks before randomization.
• Subjects who have previously been treated with more than 3 different TNF inhibitors (investigational or approved).
• Subjects who have ever received biologic immunomodulating agents, investigational or approved except for those targeting TNFα.
• Previous treatment with any cell-depleting therapies including but not limited to anti-CD20 or investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AIN457 6 mg/kg - 3 mg/kg i.v.; AIN457 6 mg/kg i.v. infusion at baseline, followed by AIN457 3 mg/kg i.v. infusion every 4 weeks starting at Week 4 through Week 48 (exposure through Week 52).	Drug: AIN457 6 mg/kg i.v.; AIN457 6 mg/kg delivered by i.v. infusion; Other Names: secukinumab; Drug: AIN457 3 mg/kg; AIN457 3 mg/kg delivered by i.v. infusion; Other Names: secukinumab
Placebo Comparator: Placebo; Matching placebo from baseline to Week 16 and switch to AIN457 3mg/kg i.v. infusion every 4 weeks through Week 48 (exposure through Week 52).	Drug: Placebo; Matching placebo to AIN457 i.v. infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With American College of Rheumatology 50 (ACR50) Response Comparison Between Treatment Groups Using Non-responder Imputation at Week 16 (Full Analysis Set)	Percentage of participants with active psoriatic arthritis (PsA) who achieved an American College of Rheumatology 50 (ACR50) response The ACR50 is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP)	Baseline up to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With American College of Rheumatology 20 (ACR20) Response Comparison Between Treatment Groups Using On-responder Imputation at Week 16 (Full Analysis Set)	Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein.	Baseline up to Week 16
Percentage of Participants With Minimal Disease Activity (MDA 5/7) Comparison Between Treatment Groups Using On-responder Imputation at Week 16 (Full Analysis Set)	MDA is assessed as 5 of the 7 following: ≤ 1 tender and swollen joint; entheseal count, PASI ≤ 1 or BSA ≤3%, PsA ≤ 15 and disease activity ≤ 20 (VAS) and HAQ-DI© ≤ 0.5	Baseline up to Week 16
Percentage of Participants With Psoriasis Area and Severity Index 90 (PASi90) Score for Patients With a >= 3% Body Surface Area Psoriasis at Baseline Using On-responder Imputation at Week 16 (Full Analysis Set)	Change from baseline of a 90% reduction in the PASI score for patients with a >= 3% body surface area psoriasis at baseline. Four body surface areas are evaluated (head, trunk and upper and lower limbs) for plaque, erythema, scaling and thickness. The degree of severity of each sign in each of the 4 body areas was assigned a score of 0 to 4. Scores ranged from 0 to 72 and higher scores represent worsening severity.	Baseline up to Week 16
Psoriatic Arthritis Disease Activity Score (PASDAS) Change From Baseline Using Mixed Model Repeated Measures (MMRM) at Week 16 (Full Analysis Set)	PASDAS is a composite measure developed to assess disease activity in Psoriatic arthritis. It is calculated by utilizing seven measures: Patient reported measures (excluding mental component) (SF-36-PCS), skin, peripheral joint counts (tender and swollen joint counts), dactylitis (LDI), enthesitis (LEI), acute phase response (CRP), and patient and physician global VAS scores. The typical score range is between 0 and 10. Smaller values on PASDAS indicate a better condition; a negative change from baseline indicates improvement.	Baseline up to Week 16
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score Change From Baseline Using Mixed Model Repeated Measures (MMRM) at Week 16 (Full Analysis Set)	The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.	Baseline up to Week 16
Short Form 36-Physical Component Summary (SF36-PCS) Score Change From Baseline Using Mixed Model Repeated Measures (MMRM) at Week 16 (Full Analysis Set)	The SF-36 is used to measure health-related quality of life with acute and chronic conditions. It consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Range of scoring is 0 -100, with higher scores indicating better health status.	Baseline up to Week 16
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Change From Baseline Using Mixed Model Repeated Measures (MMRM) at Week 16 (Full Analysis Set)	The FACIT-Fatigue is a 13 item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Response scale ranges from 0-4 and the total score range is 0 - 52. Higher scores indicate better quality of life	Baseline up to Week 16
Modified Nail Psoriasis Severity Index (mNAPSI) Score Change From Baseline Using Mixed Model Repeated Measures (MMRM) at Week 16 (Full Analysis Set)	The mNAPSI is an instrument to assess psoriatic nail involvement. Three groups of features (onycholysis and oil-drop dyshromia, pitting and crumbling) were graded on a scale from 0 to 3 for a total subscale of 0 to 9. The next 4 abnormalities (leukonychia, splinter hemorrhages, hyperkeratosis and red spots in the lunula) were graded as absent (0) or present (1) for a total subscale of 0 to 4. The total score was from 0-13 where higher scores represent worse nail disease.	Baseline up to Week 16
Percentage of Participants With Complete Resolution of Dactylitis at Week 16 Using Non-responder Imputation (Dactylitis Subset)	Dactylitis is characterized by swelling of the entire finger or toe. The Leeds Dactylitis Index (LDI) measures the ratio of the circumference of the affected (swollen) digit. The ratio of circumference is multiplied by a tenderness score, using a modification of LDI that is a binary score (1 for tender, 0 for non-tender). The LDI requires a finger circumference gauge or a dactylometer to measure digital circumference. Scores range from 0 - 20 and lower score indicates better outcome.	Baseline up to Week 16
Percentage of Participants With Complete Resolution of Enthesitis at Week 16 Using Non-responder Imputation (Enthesitis Subset (LEI))	Enthesitis is inflammation of the enthesis which is where a a tendon or ligament attaches to the bone. The Leeds enthesitis index (LEI) is a validated index that uses 6 sites for evaluation of enthesitis: lateral epicondyle humerus L + R, proximal achilles L + R and medial condyle femur L+R. If enthesitis is present at any of the 6 sites, the subject is counted as a subject with enthesitis.	Baseline up to Week 16

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2020
• Primary Completion (Actual): May 17, 2022
• Study Completion (Actual): May 17, 2022

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: December 19, 2019
• First Posted (Actual): December 24, 2019

Study Record Updates

• Last Update Posted (Actual): May 16, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: PsA; Active Psoriatic Arthritis; Intravenous secukinumab
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Joint Diseases; Spinal Diseases; Spondylarthropathies; Skin Diseases, Papulosquamous; Skin Diseases; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Immunologic Factors; Physiological Effects of Drugs; Antibodies, Monoclonal
• Other Study ID Numbers: CAIN457P12302

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