E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Psoriasis and psoriatic arthritis |
Psoriasis og psoriasisartrit |
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E.1.1.1 | Medical condition in easily understood language |
Psoriasis and psoriatic arthritis |
Psoriasis og psoriasisgigt |
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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 | 21.0 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050576 |
E.1.2 | Term | Psoriasis vulgaris |
E.1.2 | System Organ Class | 100000004858 |
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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 study has three parts, described under sub-studies.
Main objective for the cross-sectional parts (part 1 and 2): To quantify and describe a psoriasis (Pso )patient population with regards to musculoskeletal pain, the prevalence and pattern of clinical and US signs of inflammation in joints and entheses, and their impact on patient’s lives.
Main objective for the interventional part (part 3a): To determine the effect of treating psoriatic arthritis (PsA) patients identified in part 2 of the study with apremilast, with respect to decreases in US detected inflammation scores, clinical signs and symptoms and impact on patient’s lives, and the relation between these. |
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E.2.2 | Secondary objectives of the trial |
Part 1 and 2 -To identify patients within this Pso population, who have PsA by clinical and/or US criteria, which were undiagnosed prior to the study, and to describe the burden of disease and its impact on patient’s lives by clinical, US and patient-reported outcomes.
Part 3 -To determine the effect of treating the subgroup of PsA patients identified in part 2, which have dactylitis and/or ankle region enthesitis, with apremilast, with respect to decreases in MRI detected inflammation scores, and clinical signs and symptoms and impact on patient’s lives, and the relation between these. -To investigate if induction therapy with apremilast for 6 months will, also after discontinuation, cause sustained improvements in clinical, US and patient/reported outcomes, or if symptoms and clinical and US findings will reappear, documenting a need for continuous treatment in such patients. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The study has 3 parts:
Part 1: A population-based survey of Danish inhabitants, performed by the company YouGov, will by screening of approximately 10.000 Danes identify approximately 425 persons who report to have Pso with or without PsA. These will receive an e-mail invitation to an internet based questionnaire regarding demographics, skin and joint complaints, diagnosed diseases, contact to health care providers, and different aspect of psychological and physical function and wellbeing (incl. function, health-related quality of life, depression, anxiety, social participation, and sleep disturbances). In the questionnaire the participant will be asked if he/she would be interested in participating in a clinical study. Patients will also be recruited from an out-patient clinic at a dermatological department. These patients will fill out a paper-version of the questionnaire.
Part 2: Participants who accept the above mentioned invitation (estimated 273) will be seen in a Department of Rheumatology, for the following examination programme: Clinical examination with a focus on skin, joints and entheses, US examination of joints and entheses, patient-reported outcomes and blood sampling for both stratification and identification of biochemical signs of inflammation. Patients with musculoskeletal pain and joint and/or entheseal inflammation documented by US (definition and criteria, see ‘definition of patient populations’ section of protocol), will be invited to participate in a 12 months’ interventional study (part 3a, below), whereas patients without musculoskeletal pain but with US findings (as above) will be invited to participate in a 12 months non-interventional follow-up study (part 3b, below). Patients with pre-diagnosed PsA that by US have active inflammation (same definition and criteria as above, see ‘definitions of patient population’ section), will also be invited to participate in the interventional study if they fit the criteria, especially those described under concomitant medication, otherwise they will be offered to participate in the non-interventional study.
Part 3a: Patients with musculoskeletal pain in relation to joints and/or entheses (that is not explained by alternative diagnosis, as assessed by including rheumatologist) and “US-defined PsA”, i.e. with certain joint and/or entheseal inflammation as documented by US (see paragraph on ‘definitions of patient populations’), will be offered inclusion in a 12 months’ interventional study, in which 6 month induction therapy with apremilast (in addition to their usual therapy) will be followed by cessation of apremilast and 6 months of observation. Patients will be followed with clinical examination, PRO’s, blood sampling and US at months 3, 6, 9 and 12. In case of early discontinuation from the study, an early discontinuation visit will be performed including PRO’s, clinical, US and biochemical examination MRI will be performed at inclusion and at 6 months follow-up in selected patients (patients with dactylitis or with enthesitis in the ankle region (Achilles enthesitis or plantar fasciitis)).
Part 3b: Patients without musculoskeletal pain but with certain joint or enthesal inflammation verified by US will be offered inclusion in a 12 months’ non-interventional study. Patients will continue their current therapy and be followed with clinical examination, patient-reported outcomes, blood sampling and US at months 3, 6, 9 and 12.
For objectives, please see section E 2.1. and E.2.2. |
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E.3 | Principal inclusion criteria |
In general (all parts of the study): • Age >18 years • Being able and willing to comply with the requirements of this protocol • Having signed informed consent Part 2: • Psoriasis, diagnosed by a physician according to patient Part 3a: • Musculoskeletal pain in relation to joints or entheses (that is not explained by alternative diagnosis, as assessed by including rheumatologist) and“US-defined PsA” (ie. with certain joint and/or entheseal inflammation as documented by US (see ‘Definitions of patient populations’ for definition)) • MRI substudy: o Clinical dactylitis or enthesitis in the ankle region (Achilles enthesitis or plantar fasciitis) o No contraindications for MRI Part 3b: • Not having musculoskeletal pain but still “US-defined PsA” (i.e. with certain joint and/or entheseal inflammation as documented by US (see ‘Definitions of patient populations’ in protocol for definition)) Patients that fulfill the inclusion criteria for part 3, but also fulfill some exclusion criteria for part 3a, but not for 3b, may be included in part 3b.
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E.4 | Principal exclusion criteria |
In general (all parts of study): • Incapability of complying with the examination program of this protocol for physical, mental or practical reasons. Part 2: • Incapability of understanding spoken or written Danish. Part 3a: • Pregnancy, pregnancy wish or breast-feeding. • Hypersensitivity to the active substance (apremilast) or any of the excipients. • Hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose • malabsorption • Severe renal failure (glomerular filtration rate (GFR) <30ml/min) • Current treatment with potent CYP3A4 enzyme inhibitors (rifampicin, phenobarbital, carbamazepin, phenytoin, perikon (“grønne lykkepiller” , Neurokan, Modigen, Calmigen, Velzina)) • Current or planned (during the study period) treatment that might cause psychiatric symptoms • Known active tuberculosis (TB) or history of incompletely treated TB. • Clinical history of serious liver disease. • Hepatitis B antigen positivity or Hepatitis C antibodies positivity at screening. • Bacterial infections requirering antibiotics (oral or intravenously) or serious viral or fungal infections within the last four weeks before screening. Treatment of such infections should be completed 4 weeks prior to screening. • Clinical history of serious immunological disease (including HIV or other congenital or aqiured immune disease) or other serious uncontrolled disease. • Current depression, previous depression, previous suicidal thoughts/tendencies or psychiatric symptoms • Conditions, including abnormal laboratory measurements, which might put the patient at an unnecessary risk by participation in the study or make data difficult to interpret. • Known inflammatory rheumatic disease other than PsA. • MRI substudy: Contraindications for MRI Part 3b: • Known inflammatory rheumatic disease other than PsA.
For allowed and disallaowed medications, please see protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part 1: YouGov Questionnaire (cross-sectional study) Primary outcome The prevalence of musculoskeletal pain in patients with Pso.
Part 2: Clinical and US assessments (cross sectional study) Primary outcome The prevalence of synovitis and enthesitis, as defined by US, in patients with Pso with and without musculoskeletal pain.
Part 3: 12 month’s follow-up study Primary outcome Change in OMERACT-EULAR Global US score of synovitis, from baseline to 6 months, in patients treated with apremilast (intervention group).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part 1: After all patients completed the questionnaire (cross-sectional study) Part 2: After last patient has been assessed in this part (cross-sectional study) Part 3: At months 6 |
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E.5.2 | Secondary end point(s) |
Part 1: YouGov Questionnaire Secondary outcomes The correlations between presence of musculoskeletal pain and patient reported outcomes of function, health related quality of life, and impact on patient’s lives (including EQ5D, HAQ and PsAID)
Part 2: Clinical and US assessments Secondary outcomes The prevalence of synovitis and enthesitis, as defined by US, at the individual 48 joints and 12 entheseal sites in patients with Pso with and without musculoskeletal pain. The correlation between clinical and US scores of synovitis and enthesitis with patient reported outcomes of pain, function and impact on patient’s lives (including pain, HAQ and PsAID). Sensitivity and specificity of screening questionnaires, with fulfillment of CASPAR criteria as gold standard, and “US defined PsA” as alternative.
Part 3: 12 month’s follow-up study Secondary and tertiary outcomes Change in “US total count of inflamed joints and entheses” from baseline to 3, 6 and 12 months, and from 6 to 12 months, in intervention and non-intervention groups. Change in patient pain on a VAS, from baseline to 6 months and from 6 to 12 months in intervention group. Change in OMERACT-EULAR Global US score of synovitis from baseline to 3 and 6 months, and from 6 to 12 months, in intervention and non-intervention groups. Change in US enthesitis activity score from baseline to 3, 6 and 12 months, and from 6 to 12 months, in intervention and non-intervention groups. Change in PRO’s (including PsAID, HAQ) from baseline to 3, 6, 9 and 12 months. The correlation between changes in clinical and US scores of synovitis and enthesitis and changes in patient reported outcomes of pain, function and impact on patient’s lives (pain, HAQ and PsAID and others), overall and in intervention and non-intervention groups. Change in various composite indices for disease activity and treatment response used in PsA (DAS28-CRP (Disease Activity Score, 28 joints, CRP)(40), PASDAS (Psoriatic Arthritis Disease Activity Score)(41), DAPSA (Disease Activity Index for Psoriatic Arthritis)(42), mCPDAI (modified Composite Psoriatic Disease Activity Index)(43), EULAR response criteria(44), ACR(American College of Rheumatology) response criteria(45) and PsARC (Psoriatic Arthritis Response Criteria)(46)) from baseline to month 3 and 6, and from month 6 to month 12. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Part 1: After all patients completed the questionnaire (cross-sectional) Part 2: After last patient has been assessed in this part (cross-sectional) Part 3: At month 3, 6 and 12 (see details above) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |