This study is designed as an extension study to the proof-of-concept trial CAIN457A2209 in patients with ankylosing spondylitis and aims to provide continuous treatment with AIN457 for patients in the core trial, to obtain safety and tolerability…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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
(Part 1) with a possible extension of a further 6 months (Part 2) in patients,
who participated in the core CAIN457A2209 phase II proof-of-concept study
Secondary outcome
* 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
Exploratory objectives
* To assess ASAS20, ASAS40 and ASAS 5/6 response and ASAS partial remission
* To assess the change in the ASAS core set (domains 1-6) as a continuous
outcome measure
(includes: BASFI, back pain & nocturnal pain, spinal mobility (measured by
chest expansion +
modified Schober test + occiput-to-wall distance)
* To evaluate BASMI scores (cervical rotation, maximal intermalleolar distance,
lumbar lateral
flexion, modified Schober index, tragus-to-wall distance)
* To evaluate BASDAI and physician global assessment
* To assess Maastricht Ankylosing Spondylitis Enthesis Score (MASES) and Leeds
enthesis index
(LEI)
* To assess the health related quality of life (HRQoL) by using SF-36 and and
the Ankylosing
Spondylitis Quality of Life Questionnaire (ASQoL)
* To evaluate patient global assessment (PGA) and pain by VAS
* To model free IL-17 levels in ankylosing spondylitis patients based on
measurements of total IL-17
* To assess MRI changes of the spine at week 28/EoS or week 56/EoS
Background summary
Ankylosing spondylitis is a frequent disease (0.1% of the population)
associated with significant morbidity and disability, and thus constitutes a
major socioeconomic burden. The first-line drug treatment of mild AS are
non-steroidal anti-inflammatory drugs (NSAIDS).
Study objective
This study is designed as an extension study to the proof-of-concept trial
CAIN457A2209 in patients with ankylosing spondylitis and aims to provide
continuous treatment with AIN457 for patients in the core trial, to obtain
safety and tolerability information, as well as additional PK data of AIN457.
Study design
This will be a multicenter, open-label, non-randomized trial without comparator
which will provide active treatment over 24 weeks initially (Part 1), with a
possible extension of a further 6 months (Part 2) to those patients who
participated in the core CAIN457A2209 study and fulfill inclusion and exclusion
criteria, in order to collect continuous safety data over a treatment period of
up to one year. All patients will receive 3 mg/kg AIN457 every 4 weeks.
Intervention
The subjects will be treated with 3 mg/kg AIN457 every 4 weeks over a period of
24 weeks initially (Part 1), with a possible extension of a further 6 months
(Part 2).
Study burden and risks
Giving blood samples can make feel a bit faint or sick, and can be
uncomfortable and cause bruising. Rarely, a small blood clot or infection could
occur at the site where the blood was taken. But this does not happen very
often. When taking the blood pressure the blood pressure cuff may feel a
little tight and might cause a small bruise on the arm.
When a dose of AIN457 is given this will be infused into the vein and may cause
slight pain, redness, bruising or itching.
Lichtstrasse 35
4056 Basel
CH
Lichtstrasse 35
4056 Basel
CH
Listed location countries
Age
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 of completing the study discontinuation visit of the core study, will
have an additional baseline visit (Visit 17) 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
OR
a. 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
><=1 unit)
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.
Exclusion criteria
Patients meeting any of the following criteria will be excluded from entry into the study:
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
(Week 16).
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-* 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,
whereby:
* 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-011591-30-NL |
| CCMO | NL30591.018.09 |