A 48 weeks, phase II, randomized, double-blind, placebo-controlled, proof of concept and dose finding study of three different dose regimens of BI 655066 administered subcutaneously in patients with ankylosing spondylitis.

Phase 2

Completed

Conditions: Ankylosing spondylitis
10003816

Registration Number: NL-OMON40442

Lead Sponsor: Boehringer Ingelheim

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 10

Inclusion Criteria

1. Male and female patients
2. Age * 18 years and * 70 years at screening
3. Definite AS based on the modified New York criteria (1984)
4. Documented disease duration * 3 months at screening
5. Active disease at screening, defined as:
a. BASDAI score (0-10) * 4, AND
b. Spinal pain level assessed by patient on NRS (0-10) * 4 (2nd question from BASDAI will be used here)
6. Have either a documented inadequate response for axial symptoms to 30 days of optimal daily doses of at least two non-steroidal anti-inflammatory drugs (NSAIDs), or documented intolerance to NSAIDs.
7. Female patients must meet at least one of the following criteria from screening visit up to End of Observation visit in the current trial:
- using adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral contraceptives, intrauterine device (IUD)
- sexually abstinent
- have a vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
- surgically sterilised (including hysterectomy)
- postmenopausal defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory)
8. Patients (males or females) receiving background MTX or Leflunomide therapy who are following the national regulatory guidelines regarding contraception.
9. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation.

Exclusion Criteria

1. Radiographic evidence of total ankylosis of the spine at screening or before (spinal X-Ray examinations at screening visit/ during screening period are not mandatory - see footnote 12 from Flow-Chart 1).
2. Patient previously treated with any biological immunomodulating agent for AS, either licensed or experimental.
3. Previous or current participation in a clinical trial testing an investigational drug for AS within 12 weeks prior to randomization (any biological immunomodulating agents are excluded).
4. Usage of any investigational drug within 30 days prior to randomization or the planned use of an investigational drug during the course of the actual study.
5. Active uveitis or inflammatory bowel disease at screening.
6. Diagnosed psoriatic arthritis at screening, satisfying the modified New York criteria.
7. Patients who had received intraarticular injection(s) with corticosteroids within 4 weeks prior to screening visit.
8. Patients who must or wish to continue the intake of restricted medications (cf.
Section 4.2.2.1) or any drug considered likely to interfere with the safe conduct of the study.
9. Major surgery performed within 8 weeks prior to screening or planned within 12 months after screening (e.g. hip replacement).
10. Chronic or relevant acute infections including HIV, viral hepatitis and tuberculosis (positive tests for HIV, HBV/HCV or positive QuantiFERON Gold testing at screening will be exclusionary).
11. Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.
12. Evidence of current or previous clinically significant disease, medical condition other than AS, finding of the medical examination (including vital signs and ECG), or laboratory value at the screening visit outside the reference range that is of clinical relevance, that in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data. This criterion provides an opportunity for the investigator to exclude patients based on clinical judgment, even if other eligibility criteria are satisfied.
13. History of allergy/hypersensitivity to a systemically administered biologic agent or its excipients.
14. History of alcohol abuse within last 12 months (intake of more than 30 g/day).
15. History of drug abuse within last 12 months or positive drug screen at screening.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary efficacy endpoint:<br /><br>* ASAS 40 response at Week 12</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Key secondary endpoint is:<br /><br>* Change in ASDAS score at Week 12 as compared to baseline<br /><br><br /><br>Secondary efficacy endpoints are:<br /><br>* ASAS 5/6 response at Week 12<br /><br>* ASAS partial remission criteria at Week 12<br /><br>* ASAS 20 response at Week 12<br /><br>* ASAS 40 response at Week 24 (EOT)<br /><br>* Change in BASDAI score at Week 12 as compared to baseline</p><br>