E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ankylosing spondylitis (AS) |
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E.1.1.1 | Medical condition in easily understood language |
ankylosing spondylitis, Bechterew´s disease |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041672 |
E.1.2 | Term | Spondylitis ankylosing |
E.1.2 | System Organ Class | 100000004859 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048398 |
E.1.2 | Term | Spondylitis ankylosing aggravated |
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 | 10002557 |
E.1.2 | Term | Ankylosing spondylitis and other inflammatory spondylopathies |
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 evaluate the impact of treatment with a non-steroidal anti-inflammatory drug (NSAID) – Celecoxib – when added to anti-tumour necrosis factor (TNF) therapy – Golimumab – as compared to anti-TNF therapy (Golimumab) alone on progression of structural damage in the spine over two years in patients with AS (Absolute progression of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) over two years of therapy (weeks 12-108) in the Phase II (core phase) of the trial) |
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E.2.2 | Secondary objectives of the trial |
• New syndesmophyte formation or progression of existing syndesmophytes after 2 years of treatment. • Improvement of disease activity, function, axial mobility and quality of life measures • Change of the bone and cartilage biomarkers serum levels and their relevance for the prediction of radiographic progression • Change of the enteric microbiome profile |
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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 |
Perfoming MRI of spine and sacroiliac joints in a subset of study patients at baseline and end of study. Aim: change of osteitis score and scores for the chronic post-inflammatory changes on magnetic resonance imaging (MRI) by Berlin MRI scoring method |
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E.3 | Principal inclusion criteria |
1. Age ≥18 years. 2. Definite diagnosis of AS according to the modified New York criteria1. 3. History of an inadequate response to ≥2 NSAIDs taken for at least 2 weeks each. 4. Active disease as defined by a BASDAI value of ≥4 at screening and baseline. 5. Presence of at least one of the following risk factors for radiographic spinal progression: • Elevated CRP (>5mg/l) at screening at the absence of reasons for elevated CRP other than AS; • Presence of ≥ 1 syndesmophyte on prior X-rays of the spine. 6. Subject is a candidate for anti-TNF therapy based on the investigator’s opinion. 7. Subject is able and willing to give a written informed consent and comply with the requirements of the study protocol. Only patients who give written informed consent will be included in the trial. 8. If female: either unable to bear children or is willing and able to practice a reliable method of contraception throughout the study and 6 months after the last dose of study drug 9. If on NSAIDs: the dose must be stable for at least 2 weeks prior to baseline. 10. If on oral steroids: the dose must not exceed 10 mg (prednisolone equivalent) per day and must be stable for at least 2 weeks prior to baseline. 11. If on methotrexate: the dose must not exceed 25 mg per week and must be stable for at least 4 weeks prior to baseline. 12. If on sulfasalazine: the dose must not exceed 3 g per day and must be stable for at least 4 weeks prior to baseline. 13. If on analgesics: the dose must be stable for at least 2 weeks prior to baseline.
Phase II of the study: 1. Achievement of at least 50% improvement or >=2 absolute points (on a 0-10 scale) reduction of the BASDAI after 12 weeks of Golimumab treatment in the Phase I.
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E.4 | Principal exclusion criteria |
- for female subjects: pregnancy or lactating. - subjects with chronic inflammatory articular disease other than SpA or systemic autoimmune disease. - history of inadequate response (primary non-response) to previous anti-TNF therapy. - treatment with any other investigational drug within 3 months of 5 half-lifes of the drug (whichever is longer) prior to Baseline visit. - history of intolerability or hypersensitivity reaction study drugs - any active current infection. History of recurrent clinically significant infection (suggestive for primary or secondary immunodeficiency). Infections requiring treatment with antibiotics within 4 weeks prior to baseline. - current clinical signs and symptoms suggestive for tuberculosis. - positive QuantiFERON®-TB Gold In-Tube test at screening and/or abnormal chest x-ray (performed at screening or within 3 months prior to screening) suggestive for past or present tuberculosis (positive x-ray). Patients with a positive QuantiFERON®-TB Gold In-Tube test but negative chest x-ray and without clinical symptoms suggestive for tuberculosis may participate in the study after initiation of standard prophylactic anti-tuberculous treatment. - chronic infection with hepatitis B or C, history of HIV infection. - malignancies - demyelinating disease (like multiple sclerosis; including myelitis) - history of cardiovascular events or high cardiovascular risk - history of GI ulceration or any clinically relevant GI bleeding, perforation, or gastric outlet obstruction. - History of a chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis). - evidence of other severe uncontrolled disorders. - diagnosis of fibromyalgia. - several abnormalities of laboratory values as defined in the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Absolute progression of syndesmophytes as measured by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) over two years (weeks 12 to 108) of therapy in the core phase of the trial. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at baseline and end of study |
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E.5.2 | Secondary end point(s) |
• New syndesmophyte formation or progression of existing syndesmophytes after 2 years of treatment. • Improvement of disease activity, function, axial mobility and quality of life measures • Change of the bone and cartilage biomarkers serum levels and their relevance for the prediction of radiographic progression • Change of cellular and humoral markers of inflammation • Change of the enteric microbiome profile |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Syndesmophyte progression at baseline and end of study. disease activity, function, axial mobility and QOL at several timepoints troughout the study (questionnaires) bone and cartilage biomarkers and biomarkers of inflammation at several timepoints enteric microbiome at baseline and end of study.
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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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 21 |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |