The purpose of this study is to determine if SAR153191 150 mg once a week (qw) SC (subcutaneous) administration is safe and effective in reducing the recurrence and symptoms of ankylosing spondylitis over a long period of time (up to 5 years).
ID
Source
Brief title
Condition
- Central nervous system infections and inflammations
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective is to assess the long term safety of SAR153191 in patients
with ankylosing spondylitis.
Secondary outcome
Secondary Objective is to assess the long term efficacy of SAR153191 by
(ASAS20).
Background summary
Ankylosing Spondylitis (AS) is a chronic, progressive inflammatory disease
characterized by inflammatory back pain, due to sacroiliitis, spondylitis and
enthesitis that affects young men and women, commonly starting in the second
and third decades of life. Traditional therapies
for AS are nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying
antirheumatic drugs (DMARDs) and physical therapy. However the above mentioned
therapies have limited efficacy. In contrast, the anti-Tumor Necrosis Factor
(anti-TNF) agents have shown better clinical efficacy in short and intermediate
* term evaluations, but 30% to 40% of patients are still anti-TNF resistant.
Interleukin-6 (IL-6) is an important cytokine for the pathogenesis of AS.
There is evidence that the inflammation in AS is at least partly mediated by
tumor necrosis factor-alpha and IL-6, as high levels of these cytokines have
been found in biopsy from sacroiliac joints of patients with AS. Also high
levels of circulating IL-6 have been found in several groups of AS patients.
Therefore blocking IL-6 signaling pathway with SAR153191, is thought to provide
beneficial effects in patients with ankylosing spondylitis.However, no IL-6 mAb
has been approved in this indication.
Study objective
The purpose of this study is to determine if SAR153191 150 mg once a week (qw)
SC (subcutaneous) administration is safe and effective in reducing the
recurrence and symptoms of ankylosing spondylitis over a long period of time
(up to 5 years).
Study design
An uncontrolled open label extension study of SAR153191 up to 5 years or until
commercially available or until discontinuation of the project whichever is
sooner. The patient will receive 150 mg of SAR153191 given once a week (qw).
Adjustment of dose is possible to 150 mg SC every other week (q2w) in case of
safety issue. The final dose regimen will be switched to the proposed top
pivotal dose regimen at time of selection.
Intervention
SAR153191 150 mg will be adminstered to all participating patients once a week
(qw) SC (subcutaneous).
Study burden and risks
De patient visits the hospital for a minimum of 27 visits and a maximum of 29
visits during the study. The first visit is the screening visit, which is
followed by a randomization visit (Day 1), a visit at week 2, 4, 6, 8, 12,
every 12 weeks starting from week 24 to week 260 and week 266. The patient can
take the opportunity to be visited at home by a home nursing service at week 2
and 6. This is arranged by the sponsor. If the patient is more comfortable to
visit the hospital, then this is not a problem. During these (hospital) visits
physical examinations will be performed, bloodsamples will be taken, an ECG
will be made, a MRI and X-rays will be performed and several questionnaires
have to be completed. Further at the beginning of the study it will be checked
if the patient does not have Tuberculosis.
Bloodsamples
During blood draws, the patient may have pain and/or bruising at the place on
the arm where blood is taken. Blood clots may form and infections may occur,
but these events are rare. The amount of blood to be drawn will be
approximately 650 mL over 266 weeks.
Study medication
Treatment with SAR153191 may increase the risk of infection including
tuberculosis (TB), due to the fact that the immune system may become weaker and
not able to fight infections as it should therefore causing bacteria, fungi, or
viruses to spread throughout thebody. It is possible that the body may develop
antibodies (proteins that your body makes when exposed to foreign substances)
to this new drug. The patient may suffer from bruises, pain or discomfort at
injection or puncture sites.
ECG, MRI and X-ray
There might only be a little discomfort, but not risk, when the
electrocardiogram electrodes are placed on the skin and the recording of the
electrocardiogram.
During the MRI the patient need not to move or change his/her position; and
this may be uncomfortable due to the AS.
Radiation exposure from an X-ray of the spine is equivalent to the amount of
radiation exposure one experiences from less than 1 year of natural background
radioation in the Netherlands.
Pregnancy
If the patient has childbearing potential, she must either have been surgically
sterilised (tuballigation or hysterectomy) at least one month prior to study
entry; or use an IUD (intrauterine device) combined with diaphragm, condom or
spermicide; or use an oral contraceptive (the pill) together with a barrier
method, in any case she must have a negative pregnancy test at the baseline
visit and every 4 weeks during the study. Males must use 2 forms of
contraception: a condom with a spermicidal gel.
Kampenringweg 45 D-E
2803 PE Gouda
NL
Kampenringweg 45 D-E
2803 PE Gouda
NL
Listed location countries
Age
Inclusion criteria
I 01. Patients with AS that have completed 12 weeks of treatment in the DRI11073 study.
I 02. Patients must give informed consent for participating in the LTS11298 study prior to any procedure related to the study.
Exclusion criteria
E 01. Any patients who experienced any adverse events leading to treatment discontinuation from the DRI11073 study.
E 02. Any abnormalities or adverse events at the last treatment visit of the DRI11073 study that per Investigator judgment would adversely affect patient*s participation in this study.
E 03. Positive pregnancy test at the last visit in the DRI 11073 study.
E 04. Breast-feeding women.
E 05. For women of childbearing potential, unwillingness to utilize adequate contraception methods or not become pregnant during the full course of the study. Adequate contraceptive measures include oral contraceptives (stable use for 2 or more cycles prior to screening) and other prescription pharmaceutical contraceptives; IUD; bilateral tubal legations; vasectomy; condom or diaphragm plus either contraceptive sponge, foam or jelly. If subject is on MTX and/ or any other concomitant medication, please follow their precautions and recommendations. For example, if a subject is on Methotrexate, which requires a longer term use of contraception, then the longer period should be used to protect safety of subject.
E 06. Men who are unwilling to utilize 2 form of contraception: a condom and a spermicidal agent.
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 | EUCTR2010-019263-11-NL |
| CCMO | NL31887.018.10 |
| Other | Zie sectie J. |