| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10002556 |
| E.1.2 | Term | Ankylosing spondylitis |
|
| 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 |
| The primary objective of the study is to evaluate the efficacy by (ASAS20) (Assessment in Ankylosing Spondylitis Working Group responses criteria) of SAR153191 in patients with AS (Ankylosing Spondylitis) |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
assessment of higher level of response ASAS40
partial remission
disease activity
range of motion
changes in MRI score
the safety and tolerability of SAR153191 in patients with AS
to document PK profile of SAR153191 in patients with AS |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
To collect DNA blood sample for the purpose of discovery; and serum sample for purpose of biomarkers discovery.
20 October 2009
Version 1 |
|
| E.3 | Principal inclusion criteria |
I 01. Patients with active AS based on the Modified New York criteria for ankylosing
spondylitis.
I 02. Patients must had an adequate trial of at least 2 different NSAIDs taking for at least 2 weeks in each case and on a stable dose for ≥2 weeks or be intolerant to NSAIDs.
I 03. Active disease must be present for ≥3 months and be present at screening and at baseline as defined:
- Bath AS Disease Activity Index (BASDAI) score of ≥4 (NRS 0-10);
- Total back pain score ≥4 (NRS 0-10).
I 04. Patients treated with corticosteroid must be on a stable dose for >2 weeks prior to baseline.
I 05. Patients treated with DMARDs: hydroxychloroquine, sulfasalazine and MTX must be on a stable dose ≥12 weeks.
I 06. Patients must give informed consent prior to any procedure related to the study. |
|
| E.4 | Principal exclusion criteria |
E 01. Male and female patients age <18 of age or ≥75 years.
E 02. Weight <50 kg for man or <45 Kg for women or >110 kg for both man or women.
E 03. BASDAI score <4 (NRS 0-10) at screening and at baseline.
E 04. Total Back Pain score <4 (NRS 0-10) at screening and at baseline.
E 05. Patients with complete fusion of the spine.
E 06. Patient who has previously participated in any clinical trial of SAR153191.
E 07. Participation in any clinical research study evaluating another investigational drug or therapy within 60 days or at least 5 half-lives, whichever is longer, of the
investigational drug, prior to the Screening Visit.
E 08. Have a history or presence of significant other concomitant illness according to the investigator’s judgment.
E 09. Conditions/situations such as:
- Patients with short life expectancy;
- Patients with conditions/concomitant diseases making them non-evaluable for the
primary efficacy endpoint;
- Requirement for concomitant treatment that could bias primary evaluation;
- Impossibility to meet specific protocol requirements;
- Patient is the Investigator or any sub-Investigator, research assistant, pharmacist,
study coordinator, other staff or relative thereof directly involved in the conduct of
the protocol;
- Uncooperative or any condition that could make the patient potentially
non-compliant with the study procedures.
E 10. Starting treatment with NSAIDs <4 weeks prior to screening or change current
treatment or dose for ≤2 weeks prior to baseline.
E 11. Treatment with oral prednisone or equivalent corticosteroids >10 mg/day within
6 weeks prior to screening.
E 12. Use of intramuscular or intra-articular corticosteroids within the last 4 weeks before screening.
E 13. Patients who had previously been treated or are currently treated with Disease
Modifying Anti-Rheumatic Drugs or with cyclosporine, azathioprine, or DMARDs
other than methotrexate, sulfasalazine and hydroxychloroquine; and must be on a stable dose for ≥12 weeks; and not to exceed the following dose:
- Methotrexate >25 mg/week;
- Hydroxychloroquine >400 mg/day;
- Sulfasalazine >3 gr/day.
E 14. Past history of non response to any anti-TNFs treatment or non response to any other biological treatment for AS.
E 15. Any past or current treatment with anti-TNFs agents or any biological agent within 3 months from screening.
E 16. Pregnant or breast-feeding women.
E 17. For women of childbearing potential, unwillingness to utilize adequate contraception or not become pregnant during the full course of the study.
E 18. History of alcohol or drug abuse within the 5 years prior to the Screening Visit.
E 19. Any subject who has had surgery within 4 weeks prior to the Screening Visit or with planned elective surgery.
E 20. History of malignancy other than effectively treated carcinoma in-situ of the cervix, or adequately treated, non-metastatic squamous or basal cell carcinoma of the skin within five years prior to Screening Visit.
E 21. Patients with a latent or active tuberculosis.
E 22. Patients with a history of Listeriosis or tuberculosis (unless documented that it was adequately treated) (see Section 10.2).
E 23. Fever (≥38°C) or persistent chronic or active recurring infection requiring treatment with antibiotics, antivirals, or antifungals within 4 weeks prior to the Screening Visit, or history of frequent recurrent infections unacceptable per investigator judgment.
E 24. Unhealed infected skin ulcers.
E 25. Received administration of any live (attenuated) vaccine within 3 months prior to the inclusion Visit (eg, varicella-zoster vaccine, oral polio, rabies).
E 26. Received vaccination with BCG within 12 months prior to screening.
E 27. Known history of Human Immunodeficiency Virus (HIV) antibody; and/or positive
Hepatitis B surface antigen (HBsAg), and/or positive Hepatitis C antibody (HCV) at
the Screening Visit.
E 28. History of recurrent herpes zoster or active herpex zoster infection.
E 29. History of prior articular or prosthetic joint infection.
E 30. History of a hypersensitivity reaction, other than localized Injection Site Reaction (ISR), to any biological molecule.
E 31. History of a hypersensitivity reaction to doxycycline, tetracycline or related compounds (until absence of traces is demonstrated in the study drug).
E 32. Uncontrolled diabetes, defined as HbA1c ≥9.0% at the Screening Visit.
E 33. History of demyelinating disease.
E 34. Patients on dialysis.
E 35. Presence of any of the following laboratory abnormalities at the Screening Visit:
- Hemoglobin <8.5g/L;
- WBC <3000/μL;
- platelet count <100 000/μL;
- neutrophils <2000/μL;
- AST or ALT >1.5 ULN
- Bilirubin >1.5 X ULN; unless the patient has been diagnosed with Gilbert disease
by genetic testing; and documented;
- Creatinine clearance <30 mL/min (according to the Cockroft formula). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint will be the percentage of patients who achieve the assessment in AS International Working Group Criteria for improvement (ASAS20) at Week 12 |
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| 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.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 41 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
The total maximum duration of participation for a patient will be 20 weeks: up to 2 weeks of screening will be followed by a 12-week double-blind treatment period and a 6-week follow-up (in case patients do not enter the Long Term extension).
The study will be considered completed for a patient at the time he/she completes all the scheduled procedures as described in (Section 12.1 of the protocol). |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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