A Phase 3 Study of Guselkumab in Subjects with Active Psoriatic Arthritis

• Register: EUCTR
• Last refreshed on: 25 May 2020
• Main ID: EUCTR2016-001224-63-CZ
• Date of registration: 30/05/2017
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: A Phase 3 Study of Guselkumab in Subjects with Active Psoriatic Arthritis
• Scientific title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Subjects with Active Psoriatic Arthritis - Discover 2
• Date of first enrolment: 01/08/2017
• Target sample size: 684
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001224-63
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Czech Republic, Estonia, Germany, Greece, Latvia, Lithuania, Malaysia, Poland, Portugal, Romania, Russian Federation, South Africa, Spain, Taiwan, Ukraine, United States

Contacts

• Name: Clinical Registry group
• Affiliation: Janssen Biologics B.V.

• Name: Clinical Registry group
• Affiliation: Janssen Biologics B.V.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Be a man or a woman at least 18 years of age
2. Have a diagnosis of PsA for at least 6 months before the first administration of study agent and meet ClASsification criteria for Psoriatic ARthritis (CASPAR) at screening
3. Have active PsA as defined by:
a. At least 5 swollen joints and at least 5 tender joints at screening and at baseline
-AND-
b. CRP =0.6 mg/dL at screening from the central laboratory.
4. Have at least 1 of the PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis
5. Have active plaque psoriasis, with at least one psoriatic plaque of =2cm diameter or nail changes consistent with psoriasis or documented history of plaque psoriasis.
6. Have active PsA despite previous non-biologic DMARD, apremilast, and/or NSAID therapy.
- Non-biologic DMARD therapy is defined as taking a non-biologic DMARD for at least 3 months or evidence of intolerance.
- Apremilast therapy is defined as taking apremilast at the marketed dose approved in the country where the study is being conducted for at least 4 months or evidence of intolerance.
- NSAID therapy is defined as taking an NSAID for at least 4 weeks or evidence of intolerance.
7. If currently using non-biologic DMARDs , subjects should have started treatment at least 3 months and the dose must be stable for at least 4 weeks before first administration of study agent and should have no serious toxic side effects attributable to the non-biologic DMARD. If currently not using MTX, SSZ, or HCQ, must not have received for at least 4 weeks before first administration of study agent. If currently not using LEF, must not have received for at least 12 weeks before first administration of study agent.
a. If using MTX, the route of administration and dose must be stable and the dose must be =25 mg/week.
b. If receiving SSZ, the dose must be = 3g/day.
c. If receiving HCQ, the dose must be =400 mg/day.
d. If receiving LEF, the dose must be =20 mg/day.
8. If currently using NSAIDs or other analgesics for PsA, subjects must be on a stable dose for at least 2 weeks before first administration of study agent. If currently not using NSAIDs or other analgesics for PsA, must not have received NSAIDs or other analgesics for PsA within 2 weeks before first administration of study agent.
9. If currently using oral corticosteroids for PsA, subjects must be on a stable dose equivalent to =10 mg of prednisone/day for at least 2 weeks before first administration of study agent. If currently not using oral corticosteroids, the subject must not have received oral corticosteroids within 2 weeks before first administration of study agent.

For additional inclusion criteria please refer to protocol section 4.1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 547
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 137

Exclusion criteria:
1. Has other inflammatory diseases that might confound the evaluations or benefit of guselkumab therapy, including but not limited to RA, axial spondyloarthritis , systemic lupus erythematosus, or Lyme disease.
2. Has previously received any biologic treatment including, but not limited to, guselkumab, ustekinumab, secukinumab (AIN457), anti-TNFa agents (such as adalimumab, etanercept, infliximab, golimumab SC or intravenous [IV], certolizumab pegol, or their respective biosimilars), tildrakizumab (MK3222), ixekizumab (LY2439821), brodalumab (AMG827), risankizumab (BI-655066), or other investigative biologic treatment for PsA or psoriasis.
3. Has ever received tofacitinib, baricitinib, filgotinib, peficitinib (ASP015K), decernotinib (VX-509), or any other Janus kinase (JAK) inhibitor.
4. Has received any systemic immunosuppressants within 4 weeks of the first administration of study agent.
5. Is currently receiving 2 or more non-biologic DMARDs specified in Table 4.
6. Has received non-biologic DMARDs (other than MTX, SSZ, HCQ, LEF) including, but not limited to chloroquine, gold preparations, and penicillamine within 4 weeks before the first administration of study agent.
7. Has received apremilast within 4 weeks prior to the first administration of study agent.
8. Has received phototherapy or any systemic medications/treatments that could affect psoriasis evaluations (including, but not limited to, retinoids, 1,25-dihydroxy vitamin D3 and analogues, psoralens, fumaric acid derivatives, with the exception of those in Table 4) within 4 weeks of the first administration of study agent.
9. Has used topical medications/treatments that could affect psoriasis evaluations within 2 weeks of the first administration of any study agent.
10. Has received epidural, intra-articular, intramuscular, or IV corticosteroids, including adrenocorticotropic hormone during the 4 weeks before first administration of study agent.
13. Has unstable suicidal ideation or suicidal behavior in the last 6 months, that may be defined as an eC-SSRS rating at screening of
? - Ideation level 4: Some intent to act (“4”), no plan; OR
? - Ideation level 5: Specific plan and intent (“5”), OR
? - Any of the following suicidal behaviors:
– actual suicide attempts
– interrupted attempts
– aborted attempts
– preparatory actions
AND is confirmed to be at risk by the investigator based on an evaluation by a mental health professional. The final decision on excluding a subject will be made at the judgment of the investigator.
35. Is seropositive for antibodies to hepatitis C virus (HCV) at screening, unless the subject had 2 negative HCV ribonucleic acid (RNA) test results at least 6 months apart prior to screening and have a third negative HCV RNA test result at screening.

For additional exclusion criteria please refer to protocol section 4.2.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Active Psoriatic Arthritis
MedDRA version: 21.0 Level: LLT Classification code 10037160 Term: Psoriatic arthritis System Organ Class: 100000004859

Intervention(s)

Product Name: Guselkumab
Product Code: CNTO1959
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Guselkumab
Current Sponsor code: CNTO1959
Other descriptive name: GUSELKUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: - Efficacy in improving psoriatic skin lesions
- Improvement in physical function
- Inhibition of progression of structural damage
- Efficacy in improving general and disease specific health-related quality of life and patient-reported health outcomes
- Safety
- Pharmacokinetics, pharmacodynamics, and immunogenicity

Timepoint(s) of evaluation of this end point: Week 24

Main Objective: To evaluate the efficacy of guselkumab treatment in subjects with active psoriatic arthritis (PsA) by assessing the reduction in signs and symptoms of PsA.

Primary end point(s): The proportion of subjects who achieve an American College of Rheumatology (ACR) 20 response at Week 24.

Secondary Outcome(s)

Secondary end point(s): 1. Change from baseline in Disability Index of the Health Assessment Questionnaire (HAQ-DI) score at Week 24.
2. Proportion of subjects who achieve an ACR 50 response at Week 24.
3. Proportion of subjects with a psoriasis response of an Investigator’s Global Assessment (IGA) (ie, an IGA psoriasis score of 0 [cleared] or 1 [minimal] AND =2-grade reduction from baseline) at Week 24 among the subjects with =3% body surface area (BSA) psoriatic involvement and an IGA score of =2 (mild) at baseline.
4. Proportion of subjects who achieve an ACR 20 response at Week 16.
5. Change from baseline in modified van der Heijde-Sharp (vdH-S) score at Week 24.
6. Proportion of subjects with resolution of enthesitis at Week 24 among the subjects with enthesitis at
baseline.
7. Proportion of subjects with resolution of dactylitis at Week 24 among the subjects with dactylitis at baseline.
8. Change from baseline in enthesitis score (based on Leeds Enthesitis Index [LEI]) at Week 24 among the subjects with enthesitis at baseline.
9. Change from baseline in dactylitis score at Week 24 among the subjects with dactylitis at baseline.
10. Change from baseline in 36-item Short Form Health Survey Physical Component Summary (SF-36 PCS) at Week 24.
11. Change from baseline in Disease Activity Score 28 (DAS28) C-reactive protein (CRP) at Week 24.
12. Change from baseline in SF-36 Mental Component Summary (MCS) at Week 24.
13. Proportion of subjects who achieve an ACR 50 response at Week 16.
14. Proportion of subjects who achieve an ACR 70 response at Week 24.

For additional secondary endpoints please refer to the protocol.

Timepoint(s) of evaluation of this end point: 1 - 3, 5 - 12, 14: Week 24
4, 13: Week 16

Secondary ID(s)

2016-001224-63-ES

CNTO1959PSA3002

Source(s) of Monetary Support

Janssen Research & Development, LLC

Ethics review

Status: Approved
Approval date: 14/06/2017
Contact: