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History of Changes for Study: NCT04209205
Study to Demonstrate the Efficacy, Safety and Tolerability of Intravenous Secukinumab up to 52 Weeks in Subjects With Active Psoriatic Arthritis (INVIGORATE 2)
Latest version (submitted July 19, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 December 19, 2019 None (earliest Version on record)
2 January 8, 2020 Study Status
3 March 10, 2020 Recruitment Status, Study Status, Contacts/Locations and Oversight
4 July 22, 2020 Study Status and Contacts/Locations
5 September 29, 2020 Study Status and Contacts/Locations
6 March 29, 2021 Study Status
7 April 28, 2021 Contacts/Locations and Study Status
8 May 10, 2021 Study Status and Contacts/Locations
9 December 2, 2021 Study Status
10 July 19, 2022 Recruitment Status, Study Status, Contacts/Locations, Study Design and Eligibility
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Study NCT04209205
Submitted Date:  December 19, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: CAIN457P12302
Brief Title: Study to Demonstrate the Efficacy, Safety and Tolerability of Intravenous Secukinumab up to 52 Weeks in Subjects With Active Psoriatic Arthritis (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
Secondary IDs:
Open or close this module Study Status
Record Verification: December 2019
Overall Status: Not yet recruiting
Study Start: December 23, 2019
Primary Completion: April 23, 2021 [Anticipated]
Study Completion: May 2, 2022 [Anticipated]
First Submitted: October 30, 2019
First Submitted that
Met QC Criteria:
December 19, 2019
First Posted: December 24, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
December 19, 2019
Last Update Posted: December 24, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Novartis Pharmaceuticals
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
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.

Open or close this module Conditions
Conditions: Psoriatic Arthritis
Keywords: Active Psoriatic Arthritis
Intravenous secukinumab
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 380 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Secukinumab
Secukinumab intravenous (i.v.) regimen
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 Names:
  • AIN457
Placebo Comparator: Placebo
Placebo intravenous (i.v.) regimen
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).
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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)

Secondary Outcome Measures:
1. 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)

2. 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
3. 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
4. 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
5. 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
6. 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.
7. 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
8. 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
9. 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
10. 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
11. 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)
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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)
Open or close this module Contacts/Locations
Central Contact Person: Novartis Pharmaceuticals
Telephone: 1-888-669-6682
Email: novartis.email@novartis.com
Central Contact Backup: Novartis Pharmaceuticals
Telephone: +41613241111
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Undecided

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

Open or close this module References
Citations:
Links:
Available IPD/Information:

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U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services