|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Ankylosing spondylitis (AS), which belongs to seronegative spondyloarthropathies (SpA).
|E.1.2 Medical condition or disease under investigation
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To assess the safety and tolerability of AIN457 in patients with moderate to severe ankylosing spondylitis receiving i.v. AIN457 initially up to 6 months (part1) with a possible extension of a further 6 months (part2) in patients who participated in the core CAIN457A2209 phase II proof-of-concept study
|Secondary objectives of the trial
|To assess the immunogenicity of AIN457
To assess the total IL-17 concentration in blood at steady-state
To assess the pharmacokinetics of AIN457 at steady state
|Trial contains a sub-study
|Principal inclusion criteria
|1. Patients who participate and complete the core CAIN457A2209 study up to and including the EoS i.e. Visit 16 (Week 24), may enter the extension study upon signing informed consent.
2. Patients who discontinued the core study due to unsatisfactory therapeutic effect at their Visit 14 (Week 16) or later may enter the extension study within three weeks of completing the study discontinuation visit of the core study, provided that at their discontinuation visit they meet the criteria below, Patients who do not enter the extension study within 3 weeks after completing the study discontinuation visit of the core study, will have an additional baseline visit (visit 18) and must meet the criteria below.
a. There is no improvement (compared with the core study baseline) in two out of the
following four domains: patient global assessment, pain, BASFI and the mean of the
two morning stiffness questions from the BASDAI
b. There is a deterioration (compared with the core study baseline) in one of the four
domains (deterioration defined as >=20% worsening and an absolute worsening of
3. Women of childbearing potential must be using simultaneously double-barrier or two highly effective methods of contraception, (e.g. intra-uterine device plus condom,
diaphragm plus condom, etc; hormone replacement as either oral or implantable is
acceptable as one form), from the time of screening for the duration of the entire study, up to study completion and up to 16 weeks post last drug administration. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
4. Male patients willing to use simultaneously two highly effective methods of contraception (e.g. intra-uterine device plus condom) for the duration of the entire study, up to study completion visit and up to 16 weeks post the last drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception.
|Principal exclusion criteria
|1. Patients for whom continued treatment with AIN457 in the extension is not considered appropriate by the treating physician.
2. Patients who were non-compliant or who demonstrated a major protocol deviation in the core CAIN457A2209 study.
3. Patients who discontinued from the core CAIN457A2209 study before Visit 14
4. Female patients who are pregnant or lactating
5. Any active systemic infection within the past 2 weeks including a positive chest X-ray.
6. Positive human immunodeficient virus (HIV: ELISA and Western blot) test result,
Hepatitis B surface antigen (HBsAg) or Hepatitis C test result, where patients have been re-tested.
The following Exclusion Criteria as defined in the core trial [CAIN457A2209] will continue to be valid with minor revisions:
7. Positive Purified Protein Derivative (PPD) tuberculin skin test of ≥ 5 mm at baseline, (where patients have been re-tested). A positive PPD test will be defined using the MMWR 2000 guidance, summarized as criteria for tuberculin positivity by risk group. A PPD test should not be done in subjects who had a tuberculosis vaccination in the past. These subjects will be eligible to participate if – according to local guidelines – latent tuberculosis can be excluded. For those study sites using QuantiFeron test a positive test at baseline (where patients have been re-tested) will exclude the subject from the participation in the study. If the result for either PPD or QuantiFeron test is indeterminate the subject will be excluded.
8. For previous use of immunosuppressive agents a wash-out period of at least 1 month or 5 half-lives, whatever is longer, is required. Immunosuppressive agent include but are not limited to cyclosporine, mycophenolate, tacrolimus, and 5-aminosalicylic acid (5-ASA).
If on previous treatment with anti-TNF-α therapy (or other biological therapy), the
following washout periods will be required for such patients to be eligible to participate in the trial.
• Six (6)-months wash out prior to dosing for alefacept, rituxan and raptiva,
• Three (3)-months washout prior to baseline for adalimumab and certolizumab,
• Two (2)-months washout prior to baseline for etanercept and infliximab,
• One (1) month washout prior to baseline for systemic immunosuppressants including, but not limited to azathioprine, cyclosporine, and leflunomide.
Patients on concomitant prednisone, methotrexate (MTX) or SSZ can be included,
• Prednisone should be kept at a stable dose 4 weeks before baseline and throughout the
study and not exceed 10 mg/day.
• MTX should be kept at a stable dose 4 weeks before baseline and throughout the
study and not exceed 25 mg/week.
• SSZ should be kept at a stable dose 4 weeks before baseline and throughout the study.
9. Patients who are on NSAIDS should be kept at a stable dose 4 weeks before baseline and throughout the study.
|E.5 End points
|Primary end point(s)
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
| Information not present in EudraCT
|Trial has a data monitoring committee
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
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days