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 | 14.0 |
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 including those previously treated with biologic anti-TNFα agent(s) 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 |
• 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:
• Have active plaque psoriasis or a documented history of plaque psoriasis.
• Have active PsA despite current or previous DMARD and/or NSAID therapy.
• Subjects previously treated with a biologic anti- TNFα agent, must have:
– received at least an 8-week dosage regimen of
etanercept, adalimumab, golimumab, or certolizumab pegol; or
– received at least a 14-week dosage regimen of
infliximab; or
– received less than an 8-week dosage regimen of etanercept, adalimumab,
golimumab, or certolizumab pegol or less than a 14-week dosage regimen of
infliximab as described above and have documented intolerance of anti-TNFα
therapy
• Women must be:
– surgically sterile
or
– abstinent, 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 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 TB screening criteria:
– Have no history of latent or active TB prior to screening. An exception is made for subjects with prior use of anti-TNFα agent(s) with a history of latent TB and documentation of having completed appropriate treatment for latent TB within 3 years prior to the first administration of study agent. It is the responsibility of the investigator to verify the adequacy of previous antituberculous treatment and provide appropriate documentation.
– 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.
• 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/mL (SI: ≥ 3.5 GI/L)
– Neutrophils ≥ 1.5 x 103/mL (SI: ≥ 1.5 GI/L)
– Platelet ≥ 100 x 103/mL (SI: ≥ 100 GI/L)
– Serum creatinine ≤ 1.5 mg/dL (SI: ≤ 129 mmol/L)
– AST, ALT, and alkaline phosphatase levels must be within 1.5 times the ULN
range for the laboratory conducting the test.
• Willing/able to adhere to the prohibitions and restrictions specified in this protocol
• Subjects must have signed an informed consent |
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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 received infliximab, golimumab, or certolizumab pegol within 12 weeks prior
to the first administration of the study agent.
• Have received adalimumab or etanercept within 8 weeks prior to the first
administration of the study agent.
• Have received alpha-4 integrin antagonists 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, administered intramuscularly 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,
• 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 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 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
• 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
• Any condition that, in the opinion of the investigator, would compromise the wellbeing of the subject or the study or prevent the subject from meeting or performing study requirements |
|
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. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. The change from baseline in the HAQ-DI score at Week 24 will be compared between the ustekinumab groups and the placebo group.
2. The proportion of subjects with ACR 50 and ACR 70 responses at Week 24 will be compared between the ustekinumab groups and the placebo group. Ustekinumab: Clinical Protocol CNTO1275PSA3002 - Amendment 3 For Approval 01 Oct 2010 64
3. The proportion of subjects (with baseline Larger then 3% BSA psoriatic involvement) who achieve a PASI 75 response at Week 24 will be compared between the ustekinumab groups and the placebo group.
4. 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.8.3 |
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 | 26 |
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 |
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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 will end when the last subject completes the Week 60 visit.
|
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |