BI 655066 (Risankizumab) Proof of Concept Dose Finding Study in Ankylosing Spondylitis (AS)

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.

The overall purpose of the trial is to assess the clinical efficacy of three different subcutaneous doses of BI 655066 (risankizumab) in adult patients with AS, in order to provide clinical proof of concept and to select dose (s) for confirmatory clinical trials.

Inclusion criteria:

1. Male and female patients

2. Age = 18 years and = 70 years

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:

   1. BASDAI score (0-10) = 4, AND
   2. Spinal pain level assessed by the 2nd BASDAI question (0-10) = 4

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 who meet any of the following criteria from screening visit up to the End of Observation visit (EOO):

   • 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

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 XRay 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 at screening will be exclusionary)

    For tuberculosis patients, they are not eligible according to the following screening criteria:

    • Have signs or symptoms suggestive of current active or latent TB upon medical history, physical examination and/or a chest radiograph (both posterior-anterior and lateral views, taken within 3 months prior to the first administration of study drug and read by a qualified radiologist)
    • Have history of latent or active TB prior to screening, except for patients who have documentation of having completed an adequate treatment regimen at least 6 months prior to the first administration of study agent
    • Have positive QuantiFERON-TB Gold In-Tube test within 2 months prior to or during screening, in which active TB has not been ruled out, except for patients with history of latent TB and documentation of having completed an adequate treatment regimen at least 6 months prior to the first administration of study agent

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