Clinical trial NCT04209205: Study to Demonstrate the Efficacy, Safety and Tolerability of Intravenous Secukinumab up to 52 Weeks in Subjects With Active Psoriatic Arthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriatic Arthritis
Keywords: Active Psoriatic Arthritis
Intravenous secukinumab
PsA
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-12-24
Enrollment: 381
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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)
timeFrame: Baseline up to Week 16
Secondary outcomes:
measure: 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)
timeFrame: Baseline up to Week 16
measure: Percentage of Participants With Minimal Disease Activity (MDA 5/7) Comparison Between Treatment Groups Using On-responder Imputation at Week 16 (Full Analysis Set)
timeFrame: Baseline up to Week 16
measure: 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)
timeFrame: Baseline up to Week 16
measure: Psoriatic Arthritis Disease Activity Score (PASDAS) Change From Baseline Using Mixed Model Repeated Measures (MMRM) at Week 16 (Full Analysis Set)
timeFrame: Baseline up to Week 16
measure: Health Assessment Questionnaire - Disability Index (HAQ-DI) Score Change From Baseline Using Mixed Model Repeated Measures (MMRM) at Week 16 (Full Analysis Set)
timeFrame: Baseline up to Week 16
measure: Short Form 36-Physical Component Summary (SF36-PCS) Score Change From Baseline Using Mixed Model Repeated Measures (MMRM) at Week 16 (Full Analysis Set)
timeFrame: Baseline up to Week 16
measure: 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)
timeFrame: Baseline up to Week 16
measure: Modified Nail Psoriasis Severity Index (mNAPSI) Score Change From Baseline Using Mixed Model Repeated Measures (MMRM) at Week 16 (Full Analysis Set)
timeFrame: Baseline up to Week 16
measure: Percentage of Participants With Complete Resolution of Dactylitis at Week 16 Using Non-responder Imputation (Dactylitis Subset)
timeFrame: Baseline up to Week 16
measure: Percentage of Participants With Complete Resolution of Enthesitis at Week 16 Using Non-responder Imputation (Enthesitis Subset (LEI))
timeFrame: Baseline up to Week 16
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Fountain Valley
country: United States
facility: Novartis Investigative Site
state: California
city: Fullerton
country: United States
facility: Novartis Investigative Site
state: California
city: La Mesa
country: United States
facility: Novartis Investigative Site
state: California
city: Santa Monica
country: United States
facility: Novartis Investigative Site
state: California
city: Upland
country: United States
facility: Novartis Investigative Site
state: California
city: Van Nuys
country: United States
facility: Novartis Investigative Site
state: California
city: West Hills
country: United States
facility: Novartis Investigative Site
state: California
city: Denver
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Clearwater
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Ocoee
country: United States
facility: Novartis Investigative Site
state: Florida
city: Plantation
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tampa
country: United States
facility: Novartis Investigative Site
state: Florida
city: Winter Park
country: United States
facility: Novartis Investigative Site
state: Florida
city: Marietta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Indianapolis
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Bowling Green
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Lincoln
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Voorhees
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Rochester
country: United States
facility: Novartis Investigative Site
state: New York
city: Greensboro
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Middleburg Heights
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Tulsa
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Duncansville
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Jackson
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Mesquite
country: United States
facility: Novartis Investigative Site
state: Texas
city: Newport News
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Salvador
country: Brazil
facility: Novartis Investigative Site
state: BA
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Burgas
country: Bulgaria
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
state: Atlantico
city: Bucaramanga
country: Colombia
facility: Novartis Investigative Site
state: Santander
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Cundinamarca
country: Colombia
facility: Novartis Investigative Site
city: Prague 2
country: Czechia
facility: Novartis Investigative Site
city: Praha 4
country: Czechia
facility: Novartis Investigative Site
city: Praha 5
country: Czechia
facility: Novartis Investigative Site
city: Uherske Hradiste
country: Czechia
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala
country: Guatemala
facility: Novartis Investigative Site
city: Surat
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Nashik
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Seremban
country: Malaysia
facility: Novartis Investigative Site
state: Negeri Sembilan
city: Kuching
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Selangor Darul Ehsan
country: Malaysia
facility: Novartis Investigative Site
city: Lipa City
country: Philippines
facility: Novartis Investigative Site
state: Batangas
city: Dasmarinas
country: Philippines
facility: Novartis Investigative Site
state: Cavite
city: Manila
country: Philippines
facility: Novartis Investigative Site
city: Quezon City
country: Philippines
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
state: Malopolskie
city: Karwiany
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Sochaczew
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Kemerovo
country: Russian Federation
facility: Novartis Investigative Site
city: Nizhny Novgorod
country: Russian Federation
facility: Novartis Investigative Site
city: Rostov On Don
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Yaroslavl
country: Russian Federation
facility: Novartis Investigative Site
city: Yekaterinburg
country: Russian Federation
facility: Novartis Investigative Site
city: Panorama
country: South Africa
facility: Novartis Investigative Site
state: Western Cape
city: Stellenbosch
country: South Africa
facility: Novartis Investigative Site
city: Bangkoknoi
country: Thailand
facility: Novartis Investigative Site
state: Bangkok
city: Songkhla
country: Thailand
facility: Novartis Investigative Site
state: Hat Yai
city: Khon Kaen
country: Thailand
facility: Novartis Investigative Site
state: THA
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bursa
country: Turkey
facility: Novartis Investigative Site
state: Gorukle
Study officials:
References: