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

• ClinicalTrials.gov Identifier: NCT04209205
• Recruitment Status: Recruiting
• First Posted: December 24, 2019
• Last Update Posted: May 11, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: October 30, 2019
• First Posted Date: December 24, 2019
• Last Update Posted Date: May 11, 2021
• Actual Study Start Date: January 29, 2020
• Estimated Primary Completion Date: July 14, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 19, 2019)

Proportion of subjects achieving American College of Rheumatology 50 (ACR50) response criteria [ Time Frame: Week 16 ]

To demonstrate that the efficacy of i.v. secukinumab at Week 16 is superior to placebo in subjects with active psoriatic arthritis (PsA) based on the proportion of patients achieving 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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 19, 2019)

• Proportion of subjects achieving American College of Rheumatology 20 (ACR20) response [ Time Frame: Week 16 ]
  Improvement of ≥ 20% in tender and swollen joint count and ≥3 units in at least 3 of 5 domains as described in ACR50. The ACR20 is a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% 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)
• Proportion of patients achieving Minimal Disease Activity (MDA) 5/7 [ Time Frame: 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
• Proportion of subjects achieving a Psoriasis Area and Severity Index 90 (PASI90) response [ Time Frame: Week 16 ]
  Change from baseline for PASI90, 4 items measured in 4 body areas to reflect psoriasis lesional burden (Range 0-72). Higher scores represent worsening severity
• Change from baseline for the PsA Disease Activity Score (PASDAS) [ Time Frame: Week 16 ]
  Change from baseline for PASDAS (Range: 0-10), with higher scores indicating worse disease activity
• Change from baseline for the Health Assessment Questionnaire - Disability Index (HAQ-DI) [ Time Frame: Week 16 ]
  Change from baseline for HAQ-DI (Range: 0-3). Higher scores indicate severe disability
• Change from baseline for the Short Form 36-Physical Component Summary (SF36-PCS) [ Time Frame: Week 16 ]
  Change from baseline for SF36-PCS (Range: 0-100), with higher scores indicating better health status.
• Change from baseline for the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: Week 16 ]
  Change from baseline for FACIT-F on 0-4 response scale. Range: 0-52. Higher scores indicate better quality of life
• Change from baseline for the Modified Nail Psoriasis Severity Index (mNAPSI) [ Time Frame: Week 16 ]
  7 groups of features for each fingernail (Score: 0-130). Higher scores represent worse nail disease
• Proportion of subjects with dactylitis in the subset of subjects who have dactylitis at baseline [ Time Frame: Week 16 ]
  Finger size and tenderness (Range 0-20). A higher score implies worse dactylitis
• Proportion of subjects with enthesitis in the subset of subjects who have enthesitis at baseline [ Time Frame: Week 16 ]
  6 enthesial sites and tenderness (Range: 0 -6). Higher count implies greater enthesitis burden
• Assessment of safety and tolerability of i.v. secukinumab compared to placebo [ Time Frame: Week 16 ]
  The incidence of clinically significant abnormal laboratory values/test results and adverse, serious adverse events (by review of values outside clinically notable ranges, significant changes from Baseline or the previous visit, or values, which are considered to be non-typical in participants with underlying disease)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Brief Summary: This study 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 NSAID, DMARD and/or anti-TNF therapy.

Detailed Description

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

At baseline, approximately 380 patients with active psoriatic arthritis will be randomized to one of the two treatment groups in a 1:1 randomization:

Group 1: Approximately 190 patients with active psoriatic arthritis; These patients will receive 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 will receive 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 will consist 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
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

This is a double-blind, randomized treatment trial.

Subjects, investigator staff, persons performing the assessments will remain blinded to the identity of the treatment from the time of randomization until Week 60 database lock, using the following methods:

1. Randomization data are kept strictly confidential until the time of unblinding and will not be accessible by anyone else involved in the study with the exception of the bioanalyst.
2. The identity of the treatments will be concealed by the use of study treatments in the form of i.v. injection, filled with secukinumab or placebo that are identical in appearance.

Primary Purpose: Treatment

• Condition: Psoriatic Arthritis

Intervention

• Drug: Secukinumab
  Subjects will receive secukinumab i.v. (6 mg/kg) at BSL, followed by secukinumab 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through week 52).
  Other Name: AIN457
• Drug: Placebo
  Subjects will receive placebo i.v. at BSL, Week 4, 8 and 12 followed by secukinumab 3 mg/kg i.v. every four weeks starting at Week 16 through Week 48 (exposure through week 52).

Study Arms

• Experimental: Secukinumab
  Secukinumab intravenous (i.v.) regimen
  Intervention: Drug: Secukinumab
• Placebo Comparator: Placebo
  Placebo intravenous (i.v.) regimen
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 19, 2019): 380
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 18, 2022
• Estimated Primary Completion Date: July 14, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Patients eligible for inclusion in this study have 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

• Listed Location Countries: Brazil, Bulgaria, Colombia, Czechia, Greece, Guatemala, India, Malaysia, Philippines, Poland, Russian Federation, South Africa, Thailand, Turkey, United States

Administrative Information

• NCT Number: NCT04209205
• Other Study ID Numbers: CAIN457P12302
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

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

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Study Sponsor: Novartis Pharmaceuticals
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: May 2021