E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037160 |
E.1.2 | Term | Psoriatic arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 objectives of this study are to evaluate the efficacy of ustekinumab in subjects with active PsA by assessing the reduction in signs and symptoms of PsA and to evaluate the safety of ustekinumab in this population. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate the efficacy of ustekinumab in:
1. Improving physical function;
2. Improving psoriatic skin lesions; and
3. Inhibiting the progression of structural damage. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Potential subjects must satisfy all of the following criteria to be enrolled in the study:
• Men or women between 18 and 99 years of age, inclusive.
• Have had PsA at least 6 months prior to the first administration of study agent.
• Have a diagnosis of active PsA as defined by:
– 5 or more swollen joints and 5 or more tender joints at screening and at baseline
-AND- C-reactive protein (CRP) ≥ 0.3 mg/dL at screening.
• Have at least 1 of the PsA subsets: DIP joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis.
• Have active plaque psoriasis or a documented history of plaque psoriasis.
• Have active PsA despite current or previous DMARD and/or NSAID therapy. DMARD therapy is defined as taking a DMARD for at least 3 months, or evidence of DMARD intolerance. NSAID therapy is defined as taking an NSAID for at least 4 weeks or evidence of NSAID intolerance.
• Women must be:
– surgically sterile, or
– abstinent (at the discretion of the investigator/per local regulations), or
– if sexually active, be practicing a highly effective method of birth control as local regulations permit, before entry, and must agree to continue to use the same method of contraception throughout the study.
• Women of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at screening; and a negative urine pregnancy test at Week 0.
• Men capable of fathering children must agree to use a double barrier method of birth control (or must have been surgically sterilized) and to not donate sperm during the study and for 15 weeks after receiving the last dose of study drug.
• Are considered eligible according to the following tuberculosis (TB) screening criteria:
– Have no history of latent or active TB prior to screening.
– Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
– Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study agent.
– Within 6 weeks prior to the first administration of study agent, have a negative QuantiFERON-TB Gold test result, or have a newly identified positive QuantiFERON-TB Gold test result in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent.
– Have a chest radiograph taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current, active TB or old, inactive TB
• If using MTX, subjects should have started treatment at a dose not to exceed 25 mg/week at least 3 months prior to the first administration of study agent and should have no serious toxic side effects attributable to MTX. MTX route of administration and doses should be stable for at least 4 weeks prior to the first administration of study agent. If currently not using MTX, must have not received MTX for at least 4 weeks prior to the first administration of the study agent.
• If using NSAIDs or other analgesics for PsA, must be on a stable dose for at least 2 weeks prior to the 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 for at least 2 weeks prior to the first administration of the study agent.
• If using oral corticosteroids, the subject must be on a stable dose equivalent to ≤ 10 mg of prednisone/day for at least 2 weeks prior to the first administration of study agent. If currently not using oral corticosteroids, the subject must not have received oral corticosteroids for at least 2 weeks prior to the first administration of study agent.
• Must avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during study.
• Have screening laboratory test results within the following parameters:
− Hemoglobin ≥ 8.5 g/dL (SI: ≥ 85 g/L)
− White blood cells ≥ 3.5 x 103/μL (SI: ≥ 3.5 GI/L)
− Neutrophils ≥ 1.5 x 103/μL (SI: ≥ 1.5 GI/L)
− Platelets ≥ 100 x 103/μL (SI: ≥ 100 GI/L)
− Serum creatinine ≤ 1.5 mg/dL (SI: ≤ 129 μmol/L)
• Willing/able to adhere to the prohibitions and restrictions specified in this protocol.
• Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. |
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E.4 | Principal exclusion criteria |
Have other inflammatory diseases that might confound the evaluations of benefit of ustekinumab therapy.
• Are pregnant, nursing, or planning a pregnancy or fathering a child while enrolled in the study or within 15 weeks after receiving the last administration of study agent.
• Have used any therapeutic agent targeted at reducing IL-12 or IL-23.
• Have used any investigational drug within the previous 4 weeks or 5 times the t1/2 of the investigational agent, whichever is longer.
• Have used any biologic agents that are targeted for reducing TNFα, including but not limited to infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol.
• Have received natalizumab, efalizumab, or agents that deplete B or T cells within 12 months of screening, or, if after receiving these agents, evidence is available at screening of persistent depletion of the targeted lymphocyte population.
• Have used alefacept within 3 months prior to the first administration of study agent.
• Have received abatacept.
• Known allergies, hypersensitivity, or intolerance to ustekinumab or its excipients.
• Have received DMARDs other than MTX or anakinra within 4 weeks prior to the first administration of the study agent.
• Have received leflunomide within 4 weeks prior to the first administration of study agent or have received leflunomide from 4 to 12 weeks prior to the first administration of study agent and have not undergone a drug elimination procedure.
• Have received any systemic medications/treatments that could affect psoriasis or PASI evaluation within 4 weeks of the first administration of study agent.
• Have used topical medications/treatments that could affect psoriasis or PASI evaluation (including, but not limited to corticosteroids (with the exception of low potency corticosteroids used on the palms, soles, face and/or intertriginous areas), anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, trimethylpsoralens) within 2 weeks of the first administration of study agent.
• Have received any systemic immunosuppressives within 4 weeks of the first administration of the study agent.
• Have received intra-articular, IM, or IV corticosteroids during the 4 weeks prior to the first administration of the study agent.
• Are currently receiving lithium or have received lithium within 4 weeks of the first administration of the study agent.
• Have received, or are expected to receive, any live virus or bacterial vaccination within 3 months prior to the first administration of study agent, during the study, or within 12 months after the last administration of study agent.
• Have a history of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic chest infection recurrent urinary tract infection, or open, draining, or infected skin wounds or ulcers.
• Have a history of an infected joint prosthesis, or have received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced.
• Have had or have a serious infection, or have been hospitalized or received IV antibiotics for an infection during the 2 months prior to screening.
• Have a history of latent TB or a history of or clinically active granulomatous infection, including TB, histoplasmosis or coccidioidomycosis, prior to screening.
• Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening.
• Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including TB.
• Have or ever had a nontuberculous mycobacterial infection or opportunistic infection.
• Have indeterminate initial and repeat QuantiFERON-TB Gold test results or a newly positive QuantiFERON-TB Gold (or tuberculin skin) test and refuses TB prophylaxis treatment.
• Have or have had a herpes zoster infection within 2 months of first administration of study agent.
• Are known to be infected with HIV, hepatitis B, or hepatitis C.
• Have current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease.
• Have a transplanted organ
• Have a known history of lymphoproliferative disease.
• Have any known malignancy or have a history of malignancy
• Are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access to veins.
• Are known to have had a substance abuse problem within the previous 12 months.
• Are participating in another study using an investigational agent or procedure during participation in the study.
• Are currently receiving venom immunotherapy |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of subjects achieving 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) |
The change from baseline in the HAQ-DI score at Week 24;
The proportion of subjects with ACR 50 and ACR 70 responses at Week 24;
The proportion of subjects (with baseline Larger then 3% body surface area [BSA] psoriatic involvement) who achieve a PASI 75 response at Week 24; and
The change from baseline in total radiographic scores of the hands and feet at Week 24 will be compared between the ustekinumab groups and the placebo group.This analysis will be based on a meta-analysis on pooled data from CNTO1275PSA3001 and CNTO1275PSA3002. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | Yes |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 53 |
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 |
Austria |
Canada |
Denmark |
Finland |
Germany |
Hungary |
Latvia |
Lithuania |
New Zealand |
Poland |
Russian Federation |
United Kingdom |
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
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The study is considered completed with the last visit of the last subject participating in the study |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |