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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04209205
• Collaborator: (none)
• Enrollment: 381
• Locations: 81
• Arms: 2
• Actual Duration (Months): 28.1
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Psoriatic Arthritis	Drug: Secukinumab; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 381 participants
• 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: 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. 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
• 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
• Actual Study Start Date: Jan 12, 2020
• Actual Primary Completion Date: May 17, 2022
• Actual Study Completion Date: May 17, 2022

Arms and Interventions

Arm	Intervention/Treatment
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).

Outcome Measures

Primary Outcome Measures

1. Proportion of subjects achieving American College of Rheumatology 50 (ACR50) response criteria [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 [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 [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 [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) [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) [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) [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) [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) [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 [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 [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 [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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Birmingham	Alabama	United States	35205
2	Novartis Investigative Site	Fountain Valley	California	United States	92708
3	Novartis Investigative Site	Fullerton	California	United States	92835
4	Novartis Investigative Site	La Mesa	California	United States	91942
5	Novartis Investigative Site	Santa Monica	California	United States	90404
6	Novartis Investigative Site	Upland	California	United States	91786
7	Novartis Investigative Site	Van Nuys	California	United States	91405
8	Novartis Investigative Site	West Hills	California	United States	91307
9	Novartis Investigative Site	Denver	Colorado	United States	80230
10	Novartis Investigative Site	Clearwater	Florida	United States	33765
11	Novartis Investigative Site	Miami	Florida	United States	33032
12	Novartis Investigative Site	Ocoee	Florida	United States	34761
13	Novartis Investigative Site	Plantation	Florida	United States	33324
14	Novartis Investigative Site	Tampa	Florida	United States	33624
15	Novartis Investigative Site	Winter Park	Florida	United States	32789
16	Novartis Investigative Site	Marietta	Georgia	United States	30060
17	Novartis Investigative Site	Indianapolis	Indiana	United States	46256
18	Novartis Investigative Site	Bowling Green	Kentucky	United States	42101
19	Novartis Investigative Site	Saint Louis	Missouri	United States	63117
20	Novartis Investigative Site	Lincoln	Nebraska	United States	68516
21	Novartis Investigative Site	Voorhees	New Jersey	United States	08043
22	Novartis Investigative Site	Rochester	New York	United States	14642
23	Novartis Investigative Site	Greensboro	North Carolina	United States	27408
24	Novartis Investigative Site	Middleburg Heights	Ohio	United States	44130
25	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73103
26	Novartis Investigative Site	Tulsa	Oklahoma	United States	74136
27	Novartis Investigative Site	Duncansville	Pennsylvania	United States	16635
28	Novartis Investigative Site	Jackson	Tennessee	United States	38305
29	Novartis Investigative Site	Austin	Texas	United States	78731
30	Novartis Investigative Site	Mesquite	Texas	United States	75150
31	Novartis Investigative Site	Newport News	Virginia	United States	23608
32	Novartis Investigative Site	Salvador	BA	Brazil	40150 150
33	Novartis Investigative Site	Sao Paulo	SP	Brazil	04266 010
34	Novartis Investigative Site	Burgas		Bulgaria	8000
35	Novartis Investigative Site	Plovdiv		Bulgaria	4000
36	Novartis Investigative Site	Plovdiv		Bulgaria	4002
37	Novartis Investigative Site	Sofia		Bulgaria	1413
38	Novartis Investigative Site	Sofia		Bulgaria	1431
39	Novartis Investigative Site	Barranquilla	Atlantico	Colombia	080002
40	Novartis Investigative Site	Bucaramanga	Santander	Colombia	0001
41	Novartis Investigative Site	Bogota		Colombia	110221
42	Novartis Investigative Site	Cundinamarca		Colombia	111121
43	Novartis Investigative Site	Prague 2		Czechia	128 50
44	Novartis Investigative Site	Praha 4		Czechia	140 59
45	Novartis Investigative Site	Praha 5		Czechia	150 06
46	Novartis Investigative Site	Uherske Hradiste		Czechia	686 01
47	Novartis Investigative Site	Athens		Greece	12462
48	Novartis Investigative Site	Thessaloniki		Greece	54622
49	Novartis Investigative Site	Guatemala City		Guatemala	01010
50	Novartis Investigative Site	Guatemala		Guatemala	01001
51	Novartis Investigative Site	Guatemala		Guatemala	01010
52	Novartis Investigative Site	Surat	Gujarat	India	395009
53	Novartis Investigative Site	Bangalore	Karnataka	India	560 079
54	Novartis Investigative Site	Nashik	Maharashtra	India	422 101
55	Novartis Investigative Site	New Delhi		India	110029
56	Novartis Investigative Site	Seremban	Negeri Sembilan	Malaysia	70300
57	Novartis Investigative Site	Kuching	Sarawak	Malaysia	93586
58	Novartis Investigative Site	Selangor Darul Ehsan		Malaysia	68100
59	Novartis Investigative Site	Lipa City	Batangas	Philippines	4217
60	Novartis Investigative Site	Dasmarinas	Cavite	Philippines	4114
61	Novartis Investigative Site	Manila		Philippines	1008
62	Novartis Investigative Site	Quezon City		Philippines	1102
63	Novartis Investigative Site	Krakow	Malopolskie	Poland	30-510
64	Novartis Investigative Site	Karwiany		Poland	52-200
65	Novartis Investigative Site	Krakow		Poland	30 002
66	Novartis Investigative Site	Sochaczew		Poland	96-500
67	Novartis Investigative Site	Warszawa		Poland	02-962
68	Novartis Investigative Site	Kemerovo		Russian Federation	650029
69	Novartis Investigative Site	Nizhny Novgorod		Russian Federation	603018
70	Novartis Investigative Site	Rostov on Don		Russian Federation	344022
71	Novartis Investigative Site	Saint Petersburg		Russian Federation	197022
72	Novartis Investigative Site	St Petersburg		Russian Federation	190068
73	Novartis Investigative Site	Yaroslavl		Russian Federation	150003
74	Novartis Investigative Site	Yekaterinburg		Russian Federation	620109
75	Novartis Investigative Site	Panorama	Western Cape	South Africa	7500
76	Novartis Investigative Site	Stellenbosch		South Africa	7600
77	Novartis Investigative Site	Bangkoknoi	Bangkok	Thailand	10700
78	Novartis Investigative Site	Songkhla	Hat Yai	Thailand	90110
79	Novartis Investigative Site	Khon Kaen	THA	Thailand	40002
80	Novartis Investigative Site	Bangkok		Thailand	10400
81	Novartis Investigative Site	Bursa	Gorukle	Turkey	16059

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04209205
• Other Study ID Numbers: CAIN457P12302
• First Posted: Dec 24, 2019
• Last Update Posted: Jul 20, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Active Psoriatic Arthritis; Intravenous secukinumab
• Additional relevant MeSH terms: Arthritis; Arthritis, Psoriatic

Study Results

No Results Posted as of Jul 20, 2022