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

Psoriatic Arthritis Clinical Trial

— INVIGORATE 2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04209205
• Other study ID #: CAIN457P12302
• Status: Completed
• Phase: Phase 3
• Start date: January 29, 2020
• Est. completion date: May 17, 2022

Study information

• Verified date: August 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 381
• Est. completion date: May 17, 2022
• Est. primary completion date: May 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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 TNFa.

• 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)

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Drug:
• AIN457 6 mg/kg i.v.
AIN457 6 mg/kg delivered by i.v. infusion
• Placebo
Matching placebo to AIN457 i.v. infusion
• AIN457 3 mg/kg
AIN457 3 mg/kg delivered by i.v. infusion

Locations

Country	Name	City	State
Brazil	Novartis Investigative Site	Salvador	BA
Brazil	Novartis Investigative Site	Sao Paulo	SP
Bulgaria	Novartis Investigative Site	Burgas
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Colombia	Novartis Investigative Site	Barranquilla	Atlantico
Colombia	Novartis Investigative Site	Bogota
Colombia	Novartis Investigative Site	Bucaramanga	Santander
Colombia	Novartis Investigative Site	Cundinamarca
Czechia	Novartis Investigative Site	Prague 2
Czechia	Novartis Investigative Site	Praha 4
Czechia	Novartis Investigative Site	Praha 5
Czechia	Novartis Investigative Site	Uherske Hradiste
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Thessaloniki
Guatemala	Novartis Investigative Site	Guatemala
Guatemala	Novartis Investigative Site	Guatemala
Guatemala	Novartis Investigative Site	Guatemala City
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	Surat	Gujarat
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Malaysia	Novartis Investigative Site	Selangor Darul Ehsan
Malaysia	Novartis Investigative Site	Seremban	Negeri Sembilan
Philippines	Novartis Investigative Site	Dasmarinas	Cavite
Philippines	Novartis Investigative Site	Lipa City	Batangas
Philippines	Novartis Investigative Site	Manila
Philippines	Novartis Investigative Site	Quezon City
Poland	Novartis Investigative Site	Karwiany
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Krakow	Malopolskie
Poland	Novartis Investigative Site	Sochaczew
Poland	Novartis Investigative Site	Warszawa
Russian Federation	Novartis Investigative Site	Kemerovo
Russian Federation	Novartis Investigative Site	Nizhny Novgorod
Russian Federation	Novartis Investigative Site	Rostov On Don
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	Yaroslavl
Russian Federation	Novartis Investigative Site	Yekaterinburg
South Africa	Novartis Investigative Site	Panorama	Western Cape
South Africa	Novartis Investigative Site	Stellenbosch
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkoknoi	Bangkok
Thailand	Novartis Investigative Site	Khon Kaen	THA
Thailand	Novartis Investigative Site	Songkhla	Hat Yai
Turkey	Novartis Investigative Site	Bursa	Gorukle
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Bowling Green	Kentucky
United States	Novartis Investigative Site	Clearwater	Florida
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Duncansville	Pennsylvania
United States	Novartis Investigative Site	Fountain Valley	California
United States	Novartis Investigative Site	Fullerton	California
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Jackson	Tennessee
United States	Novartis Investigative Site	La Mesa	California
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Marietta	Georgia
United States	Novartis Investigative Site	Mesquite	Texas
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Middleburg Heights	Ohio
United States	Novartis Investigative Site	Newport News	Virginia
United States	Novartis Investigative Site	Ocoee	Florida
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Plantation	Florida
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	Santa Monica	California
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Tulsa	Oklahoma
United States	Novartis Investigative Site	Upland	California
United States	Novartis Investigative Site	Van Nuys	California
United States	Novartis Investigative Site	Voorhees	New Jersey
United States	Novartis Investigative Site	West Hills	California
United States	Novartis Investigative Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Brazil,  Bulgaria,  Colombia,  Czechia,  Greece,  Guatemala,  India,  Malaysia,  Philippines,  Poland,  Russian Federation,  South Africa,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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