E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Ankylosing spondylitis (a form of arthritis) |
|
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 | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002556 |
E.1.2 | Term | Ankylosing spondylitis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
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 |
• Part 1: To evaluate the efficacy of AIN457 at 6 weeks based ASAS20 response (ASAS includes measures of patient global assessment, inflammatory back pain, Bath Ankylosing Spondylitis Functional Index (BASFI) and morning stiffness by BASDAI).
• Part 2: To evaluate the efficacy of lower doses of AIN457 at 6 weeks based on the change in BASDAI score
|
|
E.2.2 | Secondary objectives of the trial |
• 20% and 40% improvement compared to baseline as measured by ASAS response
• ASAS 5/6 response (based on ASAS plus Bath Ankylosing Spondylitis Metrology Index (BASMI) and C reactive protein (acute phase reactant)
• Physician’s global assessment of disease activity
• Quality of Life Questionnaires (SF-36 and ASQoL)
• 44-joint count
• Maastricht Ankylosing Spondylitis Enthesis Score (MASES) and Leeds enthesis index (LEI)
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male and female patients aged 18-65
• A diagnosis of moderate to severe AS fulfilling the modified New York criteria for a diagnosis of AS and whose disease is not controlled on NSAIDS (on at least one NSAID over a period of at least 3 months at maximum dose).
|
|
E.4 | Principal exclusion criteria |
• Male or female patients who plan to conceive during the time course of the study and for 6 months following the second dose.
• Participation in any clinical trial within 4 weeks prior to initial dosing or longer.
• Previous use of immunosuppressive agents such as cyclosporine without the necessary wash-out period
• History of severe allergy to food or drugs
• Positive tuberculin test
• Total ankylosis of the spine (end stage disease)
• Patients with psoriatic arthritis |
|
E.5 End points |
E.5.1 | Primary end point(s) |
PART 1: Percentage of ASAS20 responders
PART 2: Change in BASDAI response |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• 20% and 40% improvement compared to baseline as measured by ASAS response
• ASAS 5/6 response (based on ASAS plus Bath Ankylosing Spondylitis Metrology Index (BASMI) and C reactive protein (acute phase reactant)
• Physician’s global assessment of disease activity
• Quality of Life Questionnaires (SF-36 and ASQoL)
• 44-joint count
• Maastricht Ankylosing Spondylitis Enthesis Score (MASES) and Leeds enthesis index (LEI) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At screening, baseline and weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, 24 and 28:
• 20% and 40% improvement compared to baseline as measured by ASAS response
• ASAS 5/6 response (based on ASAS plus Bath Ankylosing Spondylitis Metrology Index (BASMI) and C reactive protein (acute phase reactant)
• Physician’s global assessment of disease activity
At baseline and weeks 4, 12 and 28:
• Quality of Life Questionnaires (SF-36 and ASQoL)
• 44-joint count
• Maastricht Ankylosing Spondylitis Enthesis Score (MASES) and Leeds enthesis index (LEI) |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Proteomics, metabonomics, soluble markers |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
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.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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
|
|
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 | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |