E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ankylosing Spondylitis
Atherosclerotic cardiovascular disease |
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E.1.1.1 | Medical condition in easily understood language |
Stroke, myocardial infarction, atherosclerosis
Bechterew's disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 anti-inflammatory effects of statin therapy on vessel wall inflammation by means of FDG PET/CT in AS patients
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E.2.2 | Secondary objectives of the trial |
To evaluate the change in vessel wall inflammation in AS over a follow up period of 3 years by means of FDG PET/CT.
To determine the association between the systemic inflammation caused by AS and aorta and carotid wall inflammation in patients with AS, at baseline, after statin therapy intervention and at follow up period of three years.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects with AS
Age: ≥18 years
Diagnosis of AS (following the 1984 Modified New York Criteria for ankylosing Spondylitis (16)) + disease duration since start of first symptoms for a period of more than 3 years.
Subject agrees to the restrictions as described in paragraph 4.4.2. In brief: subjects are not permitted any alcohol or caffeine-containing food or drinks from 12 hrs prior to study visits until discharge. In addition, no strenuous exercise is permitted for 24 hrs before the study visits
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E.4 | Principal exclusion criteria |
Subjects may not enter this study if they meet the following criteria
BMI > 30.
History of diabetes mellitus/insulin use
Hypertension/use of blood pressure lowering medication
Smoking
Use of statins prior to inclusion, or contra-indications for statin use.
History of cardiovascular events
Proven or suspected bacterial infections. Recent (<1 month prior to screening) or ongoing
Serious infection requiring IV antibiotic therapy.
Recent or current treatment with medications that may have a significant effect on plaque Inflammation as measured by plaque TBR, including but not limited to: Biological based medicines (anti-TNF (ex. Infliximab), anti-IL-6 therapy (ex. Tocilizumab) or anti-IL-1 (ex. anakinra)) within 8 weeks before the baseline visit and during the study.
Any clinically significant medical condition that could interfere with the conduct of the study.
Standard contra-indications to MRI, 18FDG PET, and CT, including pregnancy and lactating women.
Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
Subject has planned cardiac surgery, PCI or carotid stenting, or major non-cardiac surgery during the course of the study period or for 14 days after the last treatment.
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E.5 End points |
E.5.1 | Primary end point(s) |
Main study parameter/endpoint
- change in Target-to-background ratio (TBR) in AS patients before and after statin therapy |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline, after 3 months of statin therapy and 1-2 years follow-up |
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E.5.2 | Secondary end point(s) |
Secondary study parameters/endpoints
AS disease duration
Medical history, medication use, prior use of DMARD’s and biologicals
Demographic parameters (age, race, gender)
Blood pressure, heart rate, body weight
Inflammatory parameters: CRP, hsCRP, BSE, IL1, Il6, TNF, IL17
Parameters of cardiovascular risk: Total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, LP(a), blood pressure, and a spite tube for extra analyses.
Changes in cellular inflammatory processes in whole blood by buffycoat isolation.
Pre-existing (concurrent) conditions (those present at the screening visit)
Vital signs (supine) and body temperature
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline, after 3 months of statin therapy and 1-2 years follow-up |
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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 | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | |
E.8.9.1 | In the Member State concerned days | |