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

Phase 3

Completed

• Conditions: Psoriatic Arthritis
• Interventions: Drug: AIN457 6 mg/kg i.v.; Drug: Placebo; Drug: AIN457 3 mg/kg

• Registration Number: NCT04209205
• Lead Sponsor: Novartis Pharmaceuticals

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.

Study Timeline

• Study First Submitted: 2019-10-30
• Study First Submitted QC: 2019-12-19
• Study First Posted: 2019-12-24
• Study Start: 2020-01-29
• Primary Completion: 2022-05-17
• Study Completion: 2022-05-17
• Disposition First Submitted: 2022-10-04
• Results First Submitted: 2023-05-08
• Status Verified: 2023-08
• Results First Submitted QC: 2024-04-23
• Last Update Submitted: 2024-04-23
• Results First Posted: 2024-04-26
• Disposition First Posted: 2024-04-26
• Last Update Posted: 2024-04-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 381

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AIN457 6 mg/kg - 3 mg/kg i.v.	AIN457 6 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).
Placebo	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).
AIN457 6 mg/kg - 3 mg/kg i.v.	AIN457 3 mg/kg	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).

Primary Outcome Measures

Name	Time	Method
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)	Baseline up to Week 16	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)

Secondary Outcome Measures

Name	Time	Method
Short Form 36-Physical Component Summary (SF36-PCS) Score Change From Baseline Using Mixed Model Repeated Measures (MMRM) at Week 16 (Full Analysis Set)	Baseline up to Week 16	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.
Modified Nail Psoriasis Severity Index (mNAPSI) Score Change From Baseline Using Mixed Model Repeated Measures (MMRM) at Week 16 (Full Analysis Set)	Baseline up to Week 16	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.
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)	Baseline up to Week 16	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
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)	Baseline up to Week 16	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.
Percentage of Participants With Minimal Disease Activity (MDA 5/7) Comparison Between Treatment Groups Using On-responder Imputation at Week 16 (Full Analysis Set)	Baseline up to Week 16	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
Psoriatic Arthritis Disease Activity Score (PASDAS) Change From Baseline Using Mixed Model Repeated Measures (MMRM) at Week 16 (Full Analysis Set)	Baseline up to Week 16	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.
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score Change From Baseline Using Mixed Model Repeated Measures (MMRM) at Week 16 (Full Analysis Set)	Baseline up to Week 16	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.
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)	Baseline up to Week 16	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.
Percentage of Participants With Complete Resolution of Dactylitis at Week 16 Using Non-responder Imputation (Dactylitis Subset)	Baseline up to Week 16	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.
Percentage of Participants With Complete Resolution of Enthesitis at Week 16 Using Non-responder Imputation (Enthesitis Subset (LEI))	Baseline up to Week 16	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.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇹🇷 Bursa, Gorukle, Turkey