EVOLUTION: Guselkumab vs Golimumab in PsA TNF Inadequate Responder Patients
Study Details
Study Description
Brief Summary
The trial is a double-blinded randomized study that will examine whether switching to a selective IL23 inhibitor (guselkumab) is more effective than switching to a second TNFi (golimumab) among patients with PsA who have an inadequate response to a TNFi.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The primary aim of the trial will be to determine, among psoriatic arthritis (PsA) patients with an inadequate response (IR) to a tumor necrosis factor inhibitor (TNFi), whether switching to a new mechanism of action (MOA), specifically guselkumab (GUS), a selective interleukin 23 inhibitor (IL23i) targeting the p19 subunit, is more effective than switching to another TNFi. The primary hypothesis of this study is that switching to a new MOA may be more effective than switching to a second TNFi. This will be the first trial to test such a switch in PsA patients. Additionally, the proposed study will address the effectiveness of a new therapy, GUS, in a clinical practice setting among patients who are TNF IR.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: GUS Guselkumab (GUS) |
Drug: Guselkumab
Guselkumab (GUS) subcutaneous injection
Other Names:
|
| Experimental: GUS and Placebo Guselkumab (GUS) and Matching Placebo |
Drug: Guselkumab
Guselkumab (GUS) subcutaneous injection
Other Names:
Drug: Placebo
Guselkumab (GUS) matching placebo subcutaneous injection
|
| Active Comparator: GOL Golimumab (GOL) |
Drug: Golimumab
Golimumab (GOL) subcutaneous injection
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Achievement of cDAPSA low disease activity [12 Months]
Clinical Disease Activity in Psoriatic Arthritis (cDAPSA): a combination score of tender joint count, swollen joint count, patient assessment of pain, and patient global assessment of disease activity. Scale from 0-154 where higher figures indicate worse status. Remission is considered ≤4 and low disease activity >4 to ≤13.
- Investigator Global Assessment of Psoriasis of Clear or Almost Clear [12 Months]
Investigator global assessment (IGA) of psoriasis. A scale of 0-4 where higher figures indicate worse status. (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe).
Secondary Outcome Measures
- Minimal Disease Activity (MDA) using PSAID-12 [6 and 12 months]
Minimal Disease Activity (MDA) defines a satisfactory state of disease activity that includes 5 domains of PsA. 5/7 of the following criteria must be satisfied for MDA: patient global ≤ 2 (0-10), patient pain ≤ 2 (0-10), PSAID-12 <4 (0-10), TJC (Tender Joint Count) ≤ 1, SJC (Swollen Joint Count) ≤ 1, BSA (Body Surface Area) ≤ 3, and Leeds Enthesitis Index ≤ 1.
- Minimal Disease Activity (MDA) using HAQ-DI [6 and 12 months]
(MDA) Minimal Disease Activity defines a satisfactory state of disease activity that includes 5 domains of PsA. Participant would need to achieve 5/7 of the following criteria: patient global ≤ 2 (0-10), patient pain ≤ 2 (0-10), HAQ-DI (Health Assessment Questionnaire Disability Index) < 0.5 (0-3), TJC (Tender Joint Count) ≤ 1, SJC (Swollen Joint Count) ≤ 1, BSA (Body Surface Area) ≤ 3, and Leeds Enthesitis Index ≤ 1.
- Change in PSAID-12 [6 and 12 months]
Psoriatic Arthritis Impact of Disease Questionnaire 12-item questionnaire (PSAID-12) Survey. The range of the final PsAID-12 value is 0-10 where higher figures indicate worse status. Negative changes from baseline indicate improvement in disease activity.
- PSAID-12 < 4 [6 and 12 months]
Psoriatic Arthritis Impact of Disease Questionnaire 12-item questionnaire (PSAID-12) Survey. The range of the final PsAID-12 value is 0-10 where higher figures indicate worse status.
- Change in DLQI [6 and 12 months]
Dermatology Life Quality Index (DLQI) is a measure of skin disease activity. Calculated score of 0-30 where higher figures indicate worse status.Negative changes from baseline indicate improvement in disease activity.
- IGA Among Patients with BSA > 3% at Baseline [6 and 12 months]
Investigator global assessment (IGA) of psoriasis among patients with BSA (Body Surface Area) >3% at baseline. A scale of 0-4 where higher figures indicate worse status. (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe).
- IGA Among Patients with IGA ≥ 2 at Baseline [6 and 12 months]
Investigator global assessment (IGA) of psoriasis among patients with IGA of 2 or more (≥ 2) at baseline. A scale of 0-4 where higher figures indicate worse status. (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe).
- Change in Promis Fatigue [6 and 12 Months]
Promis Fatigue is a measure of fatigue with a score from 8-40 where higher figures indicate worse status. A negative change indicates less overall fatigue.
- Resolution of Dactylitis [6 and 12 Months]
Dactylitis is assessed using a scoring system from 0 to 3 (0-no dactylitis, 1-mild dactylitis, 2-moderate dactylitis, and 3-severe dactylitis) for each digit. These results are summed to produce a final score ranging from 0 to 20. A higher score indicates more severe dactylitis. Resolution of dactylitis is defined as a dactylitis score of 0 with a baseline dactylitis score >0.
- Resolution of Enthesitis [6 and 12 Months]
Enthesitis is assessed using the Leeds Enthesitis Index (LEI). This measure includes the following entheses: left and right lateral epicondyle humerus, left and right medial femoral condyle, and left and right achilles tendon insertion. The total LEI score of 0-6 is based on evaluating each of these six sites as 0 or 1 based on the absence or presence of pain/tenderness. Resolution of enthesitis is defined as a enthesitis score of 0 with a baseline enthesitis score >0.
- Change in BASDAI [6 and 12 Months]
Change in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) among patients with axial disease. The BASDAI sum score ranges from 0 to 10 and higher values indicate more active disease. Negative changes from baseline indicate improvement in disease activity.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Psoriatic arthritis meeting CASPAR criteria;
-
Active psoriatic arthritis defined by the presence of at least 2 swollen joints OR 1 swollen joint and 1 site of active enthesitis OR active dactylitis involving 2 joints
-
At least one active psoriasis plaque;
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Using a TNFi or previously used a single TNFi historically and either never responded or lost response (TNF IR) and planning to switch to a new biologic therapy;
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If using a single oral small molecule/csDMARD (i.e., methotrexate, leflunomide, hydroxycloroquine, sulfasalazine, or apremilast), must be on a stable dose for 4 weeks and remain on a stable dose during the study; Only use of a single OSM/csDMARD is allowed.
-
If using NSAIDs, glucocorticoids (<10 mg daily) or topical medications for psoriasis, must be on a stable dose for 4 weeks and remain on a stable dose during the study;
-
age 18-80
Exclusion Criteria:
-
Prior exposure to golimumab or another non-TNFi biologic (IL12/23i, JAKi, an IL17i, or an IL23i);
-
An adverse event that precludes use of another TNFi (development of drug-induced SLE, allergic reaction, serious infection, heart failure symptoms, demyelination at any point during use of therapy) or any other contraindication or substantial intolerance to a TNFi;
-
Use of moderate to high dose glucocorticoids (>10 mg).
-
Already meet the primary outcome at screening or baseline
-
Currently pregnant or actively trying to conceive
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital at the University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- University of Pennsylvania
- Janssen Scientific Affairs, LLC
Investigators
- Principal Investigator: Alexis Ogdie-Beatty, MD, MSCE, University of Pennsylvania
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CNTO1959PSA3006