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] - 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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate that there is a difference between secukinumab and placebo in terms of joint synovitis response over 12 weeks as measured by the PDUS Global OMERACT-EULAR Synovitis Score (GLOESS) of the affected joints (out of 48 joints) in PsA patients with an inadequate response (IR) to non biologic DMARDs. |
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E.2.2 | Secondary objectives of the trial |
Key secondary objectives:
•To demonstrate that the efficacy of secukinumab at Week 12 is superior to placebo based on the proportion of patients achieving:
- an ACR 20 response
- an ACR 50 response
•To demonstrate that the clinical response of secukinumab at Week 12 is superior to placebo based on the change in SPARCC enthesitis index from Baseline to Week 12.
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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 |
Title: Optional PDUS Sub-study
Date: 2017-03-02
Version: 02
Objectives:
• Explore early signs of response in the skin and nails of patients with concomitant moderate-to-severe psoriasis or nail psoriasis, based on the change from Baseline of Power Doppler signal, at each evaluation time, using a semi quantitative score (0 = absence or up to 2 spots, 1 = < 25% vascularization of the plaque/nail bed, 2 = > 25% and < 50% vascularization of the plaque/nail bed, 3 = > 50% vascularization of the plaque/nail bed).
• Explore time course of response to secukinumab on PDUS dactylitis in patients with concomitant dactylitis based on the change from Baseline at each evaluation time of the elementary components involved:
synovitis (using the OMERACT-EULAR scoring system), flexor tendon tenosynovitis (using the OMERACT scoring system for evaluating the presence or absence of tenosynovitis) (Naredo et al 2013), and subcutaneous involvement (using the decrease of the thickness and the disappearance of the power Doppler signal if present (Gutierrez et al 2012)); and provide a descriptive comparison of dactylitis with the contralateral digit.
• Explore the rate of response with secukinumab between Week 4 and Week 12 assessed by clinical evaluation using dactylitis count by Leeds Dactylitis Index (LDI) and by the PDUS of dactylitis. |
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E.3 | Principal inclusion criteria |
- Patient must be able to understand and communicate with the Investigator and comply with the requirements of the study and must provide written, signed and dated informed consent before any study assessment is performed.
- Male or female patients at least 18 years of age.
- Diagnosis of PsA as per CASPAR with active PsA for at least 6 months and a TJC ≥ 3 of 78 and SJC ≥ 3 of 76 at Baseline.
- Patients must have a total synovitis PDUS score ≥ 2 and inflammation related to PD signal ≥ 1 for at least 2 (affected joints as observed via PDUS) of 48 joints at the Screening visit and at the Baseline visit (before
infusion).
- At least- At least 1 clinically-involved enthesitis site at Screening and at the Baseline visit (before infusion) defined by SPARCC index different from 0.
Other protocol defined inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
-Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process obtained within 3 months prior to Screening and evaluated by a qualified physician.
-Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor.
-Any change in the dose of oral corticosteroids in the last 4 weeks prior to the Baseline visit or use of i.v. intramuscular or intra-articular corticosteroid during the last 4 weeks prior to the enrollment visit.
-Patients who have previously been treated with TNFα inhibitors (investigational or approved).
-History of hypersensitivity to the study drug or its excipients or to drugs of similar classes.
-Previous treatment with any cell-depleting therapies including but not limited to anti CD20 investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti CD19).
-Prohibited psoriasis treatments/medications with topical corticosteroids in the last 4 weeks prior to randomization.
-Pregnant or nursing (lactating) women.
Other protocol defined exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference between secukinumab and placebo in terms of joint synovitis |
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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) |
- American College of Rheumatology (ACR)-20
- ACR-50
- Spondyloarthritis Research Consortium of Canada(SPARCC)
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | 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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 |
Argentina |
Austria |
Belgium |
Canada |
Colombia |
Czech Republic |
France |
Germany |
Hungary |
Ireland |
Italy |
Mexico |
Netherlands |
Norway |
Spain |
United Kingdom |
United States |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |