E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active psoriatic arthritis |
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MedDRA Classification |
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 |
To evaluate the 84-day clinical efficacy of 2 dose regimens of CC-10004 (20 mg per os [PO] twice per day [BID, total daily dose of 40 mg] or 40 mg PO once per day [QD], subsequent to a 7-day dose titration), compared with placebo, for the treatment of active psoriatic arthritis |
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E.2.2 | Secondary objectives of the trial |
•evaluate safety,tolerability,effect on quality of life,PD effect and estimate systemic exposure of 20mg BID & 40mg QD of CC-10004 v placebo • examine PK/PD relationship between 20mg BID & 40mg QD of CC-10004 and PD activity/clinical outcomes Exploratory: •evaluate clinical efficacy of 20mg PO BID & 40mg QD of CC-10004 v placebo Extension Phase (Secondary): •evaluate safety and tolerability of 20mg PO BID & 40mg QD of CC-10004 ASA subjects treated with CC-10004 for 168 days, and in 84-day Extension Phase in ASA subjects formerly treated with placebo •evaluate 168-day clinical efficacy of 2 dose regimens of CC-10004 (20mg PO BID or 40mg QD) for ASA •compare severity of disease at Day 169 & 85 in subjects randomized to placebo •determine effect of 20mg PO BID & 40mg PO QD of CC-10004 on quality of life in ASA subjects treated with CC-10004 for 168 days, and in 84-day Extension Phase for ASA subjects formerly treated with placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Must understand and voluntarily sign an informed consent form • Must be male or female and aged ≥ 18 years at time of consent • Must have a diagnosis of psoriatic arthritis (Moll and Wright Criteria), including symmetrical or asymmetrical peripheral joint involvement for at least 6 months • Must have active psoriatic arthritis at the time of screening and baseline as defined by: 3 or more swollen joints AND 3 or more tender joints • Must have a negative rheumatoid factor (RF) • If using methotrexate, must be on methotrexate for at least 168 days (24 weeks) and be on a stable dose for at least 56 days prior to screening and throughout the study • If using oral corticosteroids, must be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 28 days prior to screening and throughout the study • If using nonsteroidal anti-inflammatory drug (NSAID) therapy, must be on a stable dose for at least 14 days prior to screening and throughout the study • Must meet the following laboratory criteria: - Hemoglobin ≥ 9 g/dL - Hematocrit ≥ 27% - White blood cell (WBC) count ≥ 3000 /μL (≥ 3.0 X 10e9/L) and < 20,000/μL (< 20 X 10e9/L) - Neutrophils ≥ 1500 /μL (≥ 1.5 X 10e9/L) - Platelets ≥ 100,000 /μL (≥ 100 X 10e9/L) - Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L) - Total bilirubin ≤ 2.0 mg/dL - Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and alanine transaminase (ALT [serum glutamate pyruvic transaminase, SGPT]) ≤ 1.5x upper limit of normal (ULN) • Must be able to adhere to the study visit schedule and other protocol requirements • Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening (Visit 1). In addition, sexually active FCBP must agree to use TWO of the following adequate forms of contraception while on study medication: oral, injectable, or implantable hormonal contraceptives; tubal ligation; intrauterine device; barrier contraceptive with spermicide; or vasectomized partner. A FCBP must agree to have pregnancy tests every 28 days while on study medication • Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP while on study medication and for at least 84 days after taking the last dose of study medication |
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E.4 | Principal exclusion criteria |
• History of any clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major diseases • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study • Pregnant or lactating female • History of active Mycobacterium tuberculosis infection (any subspecies) within 3 years prior to the screening visit. Infections that occurred > 3 years prior to entry must have been effectively treated. • History of incompletely treated latent Mycobacterium tuberculosis infection (as indicated by a positive Purified Protein Derivative [PPD] skin test or in vitro test [T-SPOT®.TB, QuantiFERON Gold®]) • Clinically significant abnormality on the chest x-ray (CXR) at screening • Current erythrodermic, guttate, or pustular forms of psoriasis • History of infected joint prosthesis within the past 5 years • Systemic therapy for psoriasis and/or psoriatic arthritis (except for methotrexate, ≤ 10 mg/day prednisone or equivalent, and NSAIDs) including, but not limited to, sulfasalazine, leflunomide, chloroquine, hydroxychloroquine, gold compounds, parenteral corticosteroids (including intra-articular), penicillamine, cyclosporine, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, tacrolimus, azathioprine, and fumaric acid esters within 28 days of randomization and throughout the study • Topical therapy for the treatment of psoriasis including, but not limited to, topical steroids, topical vitamin A or D analog preparations, tacrolimus, pimecrolimus, or anthralin within 14 days of randomization (Note: Topical background therapy for treatment of psoriasis is allowed, except within 24 hours of a study visit, as follows: mild or moderate potency corticosteroids for treatment of the palms, face, scalp, axillae, plantar surfaces, and groin in accordance with the manufacturer’s suggested usage. Nonmedicated emollients [e.g., Eucerin®] and tar shampoo are also allowed.) • Phototherapy (ultraviolet light A [UVA], narrow-band ultraviolet light B [NB-UVB], psoralens and long-wave ultraviolet radiation [PUVA]) within 28 days prior to randomization • Etanercept use within 56 days prior to randomization • Adalimumab, efalizumab, or infliximab use within 84 days prior to randomization • Alefacept use within 168 days (24 weeks) prior to randomization • Use of intra-articular corticosteroids within 28 days prior to randomization • Use of any investigational medication within 28 days prior to randomization or 5 half-lives if known (whichever is longer) • Any clinically significant abnormality on 12-lead ECG at screening • High-risk factor(s) for, or a history of, human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus infection • History of malignancy within previous 5 years (except for treated basal-cell skin carcinoma(s) and/or fewer than 3 treated squamous-cell skin carcinomas) • Evidence of skin conditions at the time of screening visit that would interfere with evaluations of the effect of study medication on psoriasis |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects in each treatment group who achieve the American College of Rheumatology criteria for 20% improvement (ACR 20) at Day 85 (Final Treatment Phase Visit)/Early Termination from Treatment Phase Visit compared with baseline |
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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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | Information not present in EudraCT |
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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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |