E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active Psoriatic Arthritis |
|
E.1.1.1 | Medical condition in easily understood language |
Active Psoriatic Arthritis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037160 |
E.1.2 | Term | Psoriatic arthritis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the efficacy of guselkumab treatment in subjects with active PsA by assessing the reduction in signs and symptoms of PsA. |
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E.2.2 | Secondary objectives of the trial |
- Efficacy in improving psoriatic skin lesions
- Improvement in physical function
- Efficacy in improving general and disease specific health-related quality of life and patient-reported health outcomes
- Safety
- Pharmacokinetics, Pharmacodynamics, and immunogenicity |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 at screening
3. Have active PsA as defined by:
a. At least 3 swollen joints and at least 3 tender joints at screening and at baseline
-AND-
b. C-reactive protein (CRP) ≥0.3 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. Subjects may have been previously treated with up to 2 anti-TNFα agents , and must document the reason for discontinuation
a. Lack of benefit to an anti-TNFα therapy, as assessed by the treating physician, after at least 12 weeks of etanercept, adalimumab, golimumab, or certolizumab pegol therapy and/or at least a 14 week dosage regimen of infliximab. Documented lack of benefit may include inadequate improvement in joint counts, physical function, or disease activity.
b. Intolerance to an anti-TNFα biologic therapy, as assessed by the treating physician, to etanercept, adalimumab, golimumab, certolizumab pegol, or infliximab.
c. If no intolerance or lack of benefit, the reason for discontinuation must be documented.
8. 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 a MTX, SSZ, or HCQ, must have not 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.
9. 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.
10. 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 a complete overview of the inclusion criteria please refer to protocol section 4.1. (pages 45-49) |
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E.4 | Principal exclusion criteria |
1. Has other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy, including but not limited to RA, axial spondyloarthritis, systemic lupus erythematosus, or
Lyme disease.
2. Has ever received more than 2 anti-TNFα agents.
3. Has received an anti-TNF agent within the following timeframes:
a. Has received infliximab or golimumab within 8 weeks before the first administration of study agent.
b. Has received golimumab SC, adalimumab or certolizumab pegol within 6 weeks before the first administration of study agent.
c. Has received etanercept within 4 weeks before the first administration of study agent.
4. Has previously been treated with guselkumab.
5. Has previously received any biologic treatment, including, but not limited to ustekinumab, abatacept, secukinumab, tildrakizumab, ixekizumab, brodalumab, risankizumab, or other investigative biologic treatment.
6. Has previously received tofacitinib, baricitinib, filgotinib, peficitinib, decernotinib, or any other Janus kinase inhibitor.
7. Has previously received any systemic immunosuppressants within the 4 weeks of the first administration of study agent
8. Has received non-biologic DMARDs including, but not limited to chloroquine, gold preparations, and penicillamine within 4 weeks before the first administration of study agent.
9. Is currently receiving 2 or more non-biologic DMARDs at baseline.
10. Has received apremilast within 4 weeks prior to the first administration of study agent.
16. Has unstable suicidal ideation or suicidal behavior in the last 6 months, that may be defined as an electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) rating at screening of:
- ideation level 4: some intent to act no plan, or:
- ideation level 5: specific plan and intent, OR
- any of the following suicidal behaviors:
* actual suicide attempts
* interrupted attempts
* aborted attempts
* prepartory 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
38. 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 a complete overview of the inclusion criteria please refer to protocol section 4.2. (pages 60-64) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects who achieve an ACR 20 response at Week 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in 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 Global Assessment at Week 24 among subjects with ≥3% body surface area psoriatic involvement and an IGA score of ≥2 at baseline.
4. Proportion of subjects who achieve an ACR 20 response at Week 16.
5. Change from baseline in DAS28 at Week 24.
6. Proportion of subjects who achieve an ACR 70 response at Week 24.
7. Proportion of subjects who achieve an ACR 50 response at Week 16.
8. Change from baseline in 36-item short form health survey (SF-36) Physical Component Summary at Week 24.
9. Proportion of subjects with resolution of enthesitis at Week 24 among the subjects with enthesitis at baseline.
10. Change from baseline in enthesitis score at Week 24 among the subjects with enthesitis at baseline.
11. Change from baseline in SF-36 Mental Component Summary at Week 24.
12. Proportion of subjects with resolution of dactylitis at Week 24 among the subjects with dactylitis at baseline.
13. Change from baseline in dactylitis scores at Week 24 among the subjects with dactylitis at baseline.
For additional secondary endpoints please refer to the protocol, section 2.1 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 - 3, 5 - 6, 8 - 13: Week 24
4, 7: Week 16 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 56 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Czech Republic |
Germany |
Hungary |
Korea, Republic of |
Malaysia |
Poland |
Russian Federation |
Spain |
Taiwan |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 29 |