This study is designed as an extension study to the proof-of-concept trial CAIN457A2206 in patients with psoriatic arthritis 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 administered i.v. initially up
to 6 months (Part 1) with a possible extension of a further 6 months (Part 2)
in patients with psoriatic arthritis who participated in the core CAIN457A2206
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 Objective(s)
* To explore the efficacy of AIN457 administered i.v. initially up to 6 months
(Part 1) with a possible extension of a further 6 months (Part 2) as measured
by ACR response criteria, PsARC response, DAS28, MASES, SPARCC and Leeds
Dactylitis Index (LDI) basic.
* To explore the effect of AIN457 on PASI scores in patients with coexisting
psoriasis.
* To explore the quality of life in psoriatic arthritis patients by using SF-36
and HAQ.
* To model concentrations of free IL-17 based on measurements of total IL-17
and to link free levels of IL-17 to DAS28 by a preliminary AIN457 dose to DAS28
response time model to allow for dose-regimen estimations.
The results from the exploratory objectives will be presented in a supplemental
report as required.
Background summary
PsA is a chronic debilitating disease of the joints that has a significant
impact on daily life. At least 10% of patients with PsA develop severe
structural joint damage (arthritis mutilans) leading to long term disability. A
substantial number of patients do not respond to standard therapies. If AIN457
is efficacious in reducing symptoms of PsA, patients enrolled in this trial and
receiving active drug may experience this benefit.
Study objective
This study is designed as an extension study to the proof-of-concept trial
CAIN457A2206 in patients with psoriatic arthritis 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 CAIN457A2206 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 CAIN457A2206 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 a later visit 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:
* The number of tender joints is the same or more than the core study baseline OR,
* The number of swollen joints is the same or more than the core study baseline OR,
* There is no improvement compared with the core study baseline in at least three of the
following five domains: patient global assessment, physician global assessment,
patient pain assessment, Health Assessment Questionnaire and CRP.
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, upto 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
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 CAIN457A2206 study.
3. Patients who discontinued from the core CAIN457A2206 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 [CAIN457A2206] 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 | EUCTR2009-011622-34-NL |
| CCMO | NL30420.018.09 |