Clinical trial NCT02798211: Study to Evaluate the Safety and Efficacy of Secukinumab 300 mg and 150 mg in Adult Patients With Active Psoriatic Arthritis (PsA) After 16 Weeks of Treatment Compared to Placebo
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Secukinumab 300 mg and 150 mg in Adult Patients With Active Psoriatic Arthritis After 16 Weeks of Treatment Compared to Placebo and to Assess the Safety, Tolerability and Efficacy up to 52 Weeks
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Psoriatic Arthritis
Keywords: PsA
ACR
CASPAR
inflammatory arthritis
spondylitis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-06-14
Enrollment: 258
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study design displays results combined as two or more Arms/Groups. Patients assigned to Placebo arm in Treatment Period 1 (TP1) may have switched to Secukinumab 300mg in Treatment Period 2 (TP2). Summaries by group were performed cumulatively by actual treatment received (as follows) for every visit until Week 16 groups in Treatment Period 1: · Secukinumab 300mg (Group 1) · Secukinumab 150mg (Group 2) · Placebo (Group 3) For entire treatment period, summaries by treatment group were performed cumulatively by the actual treatment received (as follows) for every visit til Week 52, including patients who switched at Weeks 16, 28, 40. For safety variables · Any Secukinumab 150 mg (Group 2) · Any Secukinumab 300mg (Group 1) · Any Secukinumab (Group 3) Hence, participants who received "Placebo" in TP1 were combined with participants who received "Any Secukinumab" in "Group 3" and "Any Secukinumab 300mg" in "Group 1" in TP2. Safety is presented for the ENTIRE period, including TP1 and TP2
Primary purpose: TREATMENT

Brief summary: To demonstrate that the efficacy of secukinumab 300 mg at Week 16 was superior to placebo in adult patients with active PsA based on the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response.

Detailed description: Treatment Period 1 was defined as the period from Randomization through Week 16 (prior to the Week 16 dose). At the start of placebo-controlled Treatment Period 1, patients were randomized via Interactive Response Technology (IRT) in a 2:2:1 ratio to 1 of 3 treatment groups.

Group 1- Secukinumab 300 mg: secukinumab 300 mg (2 s.c. injections of the 150-mg dose) once weekly for 5 weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing every 4 weeks.

Group 2- Secukinumab 150 mg: secukinumab 150 mg (1 s.c. injection of the 150-mg dose and 1 s.c. injection of placebo) once weekly for 5 weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing every 4 weeks.

Group 3- Placebo: placebo (2 s.c. injections of 150 mg secukinumab placebo per dose) once per week for 5 weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing every 4 weeks.

At each study treatment visit 2 s.c. injections in the form of prefilled syringes (PFS) were administered. This was necessary to maintain the blind, as secukinumab in PFS is available in either 1.0 mL (150 mg) or 2 x 1.0 mL (300 mg). Placebo to secukinumab was also available in 1.0 mL to match the active drug.

Rescue medication was not allowed before completion of Week 16 assessments.

Treatment Period 2 patients receiving secukinumab 300 mg (Group 1) continued to receive the same dose up to Week 48.

At Weeks 16, 28, and 40 patients on secukinumab 150 mg (Group 2) were classified as responders (≥20% improvement from BL in both tender and swollen joint counts) or nonresponders.

* At Weeks 16, 28, and 40 patients on secukinumab 150 mg (Group 2) who were responders continued to receive secukinumab 150 mg (1.0 mL) plus placebo (1.0 mL) every 4 weeks until next evaluation of responder status at Weeks 28 or 40.
* Patients who did not meet the responder criteria at Week 16, 28, or 40 started receiving secukinumab 300 mg s.c. every 4 weeks and continued this dose up to Week 48.
* Patients on placebo (Group 3) regardless of their responder status started receiving secukinumab 300 mg s.c. every 4 weeks from Week 16 up to Week 48.

Eligibility criteria: Inclusion Criteria:

* Male or non-pregnant, non-lactating female patients at least 18 years of age
* 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/or anti-CCP antibodies negative at screening
* A target skin psoriatic lesion and a PASI score of 1 or greater

Exclusion Criteria:

* Chest X-ray with evidence of ongoing infectious or malignant process
* Patients who ever received biologic immunomodulating agents including those targeting TNFα, IL-6 and IL-12/23 investigational or approved

Primary outcomes:
measure: Percent of Patients Achieving American College of Rheumatology Score of at Least 20% (ACR20) Response Criteria on Secukinumab 300 mg and 150 mg vs. Placebo at Week 16
timeFrame: 16 Weeks
Secondary outcomes:
measure: Percentage of Patients With Dactylitis in the Subset of Subjects Who Have Dactylitis at Week 16
timeFrame: Week 16
measure: Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Baseline (SPARCC) at Week 16
timeFrame: 16 Weeks
measure: Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Week 16 (LEI)
timeFrame: 16 Weeks
measure: Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Week 16 (Combined SPARCC and LEI)
timeFrame: 16 Weeks
measure: Percentage of Patients Achieving ACR50 Response Criteria on Secukinumab 300 or 150 mg vs. Placebo at Week 16
timeFrame: 16 Weeks
measure: Percentage of Patients Achieving ACR70 Response Criteria on Secukinumab 300 or 150 mg vs. Placebo at Week 16
timeFrame: 16 Weeks
measure: Percentage of Patients Achieving a PASI75 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Week 16
timeFrame: 16 Weeks
measure: Percentage of Patients Achieving a PASI90 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Week 16
timeFrame: 16 Weeks
measure: Percentage of Patients Achieving a PASI100 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Week 16
timeFrame: 16 Weeks
measure: Change From Baseline to Week 16 in DAS28-CRP
timeFrame: baseline, 16 weeks
measure: Change From Baseline to Week 16 in HAQ-DI
timeFrame: 16 Weeks
Other outcomes:
measure: Number and Percentage of Patients With ACR20 Response by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)
timeFrame: up to 52 weeks
measure: Number and Percentage of Patients With ACR50, ACR70 Response by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)
timeFrame: up to 52 weeks
measure: Number and Percentage of Patients With Presence of Dactylitis by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)
timeFrame: up to 52 weeks
measure: Number and Percentage of Patients With Presence of Enthesitis by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)
timeFrame: up to 52 weeks
measure: Number and Percentage of Patients With Minimal Disease Activity Response by Visit in Entire Treatment Period (up to Week 52) (Non-responder Imputation)
timeFrame: up to 52 weeks
measure: Number and Percentage of Patients With PASI75, PASI90 and PASI100 Response by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)
timeFrame: up to 52 weeks
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Little Rock
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: El Cajon
country: United States
facility: Novartis Investigative Site
state: California
city: Fountain Valley
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facility: Novartis Investigative Site
state: California
city: La Jolla
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facility: Novartis Investigative Site
state: California
city: La Mesa
country: United States
facility: Novartis Investigative Site
state: California
city: Upland
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facility: Novartis Investigative Site
state: California
city: Aventura
country: United States
facility: Novartis Investigative Site
state: Florida
city: Clearwater
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facility: Novartis Investigative Site
state: Florida
city: DeBary
country: United States
facility: Novartis Investigative Site
state: Florida
city: Jacksonville
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facility: Novartis Investigative Site
state: Florida
city: North Naples
country: United States
facility: Novartis Investigative Site
state: Florida
city: Palm Harbor
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facility: Novartis Investigative Site
state: Florida
city: Pensacola
country: United States
facility: Novartis Investigative Site
state: Florida
city: Plantation
country: United States
facility: Novartis Investigative Site
state: Florida
city: Sarasota
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tampa
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tampa
country: United States
facility: Novartis Investigative Site
state: Florida
city: Duluth
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facility: Novartis Investigative Site
state: Georgia
city: Baltimore
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facility: Novartis Investigative Site
state: Maryland
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Worcester
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Battle Creek
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Kalamazoo
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Eagan
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Lincoln
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facility: Novartis Investigative Site
state: Nebraska
city: Las Vegas
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facility: Novartis Investigative Site
state: Nevada
city: Ridgewood
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facility: Novartis Investigative Site
state: New Jersey
city: Summit
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facility: Novartis Investigative Site
state: New Jersey
city: Albany
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facility: Novartis Investigative Site
state: New York
city: Brooklyn
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facility: Novartis Investigative Site
state: New York
city: Lake Success
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facility: Novartis Investigative Site
state: New York
city: Orchard Park
country: United States
facility: Novartis Investigative Site
state: New York
city: Potsdam
country: United States
facility: Novartis Investigative Site
state: New York
city: Saranac Lake
country: United States
facility: Novartis Investigative Site
state: New York
city: Charlotte
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facility: Novartis Investigative Site
state: North Carolina
city: Greensboro
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facility: Novartis Investigative Site
state: North Carolina
city: New Bern
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facility: Novartis Investigative Site
state: North Carolina
city: Marion
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state: Ohio
city: Perrysburg
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facility: Novartis Investigative Site
state: Ohio
city: Duncansville
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facility: Novartis Investigative Site
state: Pennsylvania
city: Philadelphia
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facility: Novartis Investigative Site
state: Pennsylvania
city: Charleston
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facility: Novartis Investigative Site
state: South Carolina
city: Greenville
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state: South Carolina
city: Orangeburg
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facility: Novartis Investigative Site
state: South Carolina
city: Jackson
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Arlington
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facility: Novartis Investigative Site
state: Texas
city: Arlington
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facility: Novartis Investigative Site
state: Texas
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Mesquite
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
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facility: Novartis Investigative Site
state: Texas
city: Salt Lake City
country: United States
facility: Novartis Investigative Site
state: Utah
city: Seattle
country: United States
facility: Novartis Investigative Site
state: Washington
city: Spokane
country: United States
facility: Novartis Investigative Site
state: Washington
city: Santurce
country: Puerto Rico
facility: Novartis Investigative Site
Study officials:
References:
citation: Nguyen T, Churchill M, Levin R, Valenzuela G, Merola JF, Ogdie A, Orbai AM, Scher JU, Kavanaugh A, Kianifard F, Rollins C, Calheiros R, Chambenoit O. Secukinumab in United States Biologic-Naive Patients With Psoriatic Arthritis: Results From the Randomized, Placebo-Controlled CHOICE Study. J Rheumatol. 2022 Aug;49(8):894-902. doi: 10.3899/jrheum.210912. Epub 2022 Apr 15.