Randomized, placebo controlled, double blind, multi-center phase II proof-of-concept study to assess the efficacy of AIN457 in patients with moderate to severe ankylosing spondylitis - CAIN457A2209

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-002631-33-GB
• Date of registration: 25/07/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Randomized, placebo controlled, double blind, multi-center phase II proof-of-concept study to assess the efficacy of AIN457 in patients with moderate to severe ankylosing spondylitis - CAIN457A2209
• Scientific title: Randomized, placebo controlled, double blind, multi-center phase II proof-of-concept study to assess the efficacy of AIN457 in patients with moderate to severe ankylosing spondylitis - CAIN457A2209
• Date of first enrolment: 14/01/2009
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-002631-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany, Netherlands, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Males or females, aged 18-65 at time of consent.
2. Patients with moderate to severe AS fulfilling the modified New York criteria for a
diagnosis of AS and whose disease is not controlled on NSAIDS (on at least one NSAID over a period of at least 3 months at maximum dose). Minimum disease activity for inclusion of patients will be assessed based on the ASAS core set domains: back pain & nocturnal pain score = 4 despite concurrent NSAID use, PLUS a BASDAI score = 4. Elevated CRP or ESR are not mandatory for study inclusion.
3. Female subjects must have negative pregnancy test results at screening and baseline. WoCBP must be using simultaneously double-barrier or two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc., hormone contraception as either oral or implantable is acceptable as one form), from the time of screening and for the duration of the study, through study completion and 6 months post last dose of AIN457. Women on hormone contraception should be on this regimen for at least 2 months prior to study start.
Postmenopausal females must have had no regular menstrual bleeding for at least
two (2) years prior to initial dosing. If menopause is confirmed by a plasma FSH level of > 40 IU/L at screening, or consistent with menopause per local laboratory, pregnancy test will be required at screening, baseline, before the second infusion and monthly during the study.
Female subjects who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and/or Principle Investigator and noted in the Relevant Medical History / Current Medical Conditions section of the CRF.
If female subjects have male partners who have undergone vasectomy, the vasectomy must have occurred more than six (6) months prior to first dosing.
Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
4. Male subjects willing to use simultaneously two acceptable methods of contraception (e.g. spermicidal gel plus condom) for entire duration of the study and at least 6 months post last dose of AIN457.
5. Able to communicate well with the investigator, and to understand and comply with the requirements of the study. Understand and sign the written informed consent.
6. No evidence of liver disease or liver injury as indicated by abnormal liver function tests such as SGOT (AST), SGPT (ALT), ? GGT, alkaline phosphatase, or serum bilirubin. The investigator should be guided by criteria as outlined under exclusion criteria.
7. Patients with a history of immunization against influenza (within past 12 months) and/or history of pneumococcal vaccination will be included. If not already immunized,
vaccination is allowed to be completed (during flu season only) and such patients may be included after a 3-week window post immunization. Immunizations with attenuated life virus should be postponed until after completion of the study.
8. History or presence of psoriasis or inflammatory bowel disease will be recorded.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. WoCBP who are not willing to follow the restrictions in inclusion criteria 3, are not allowed in the study. Men who are not willing to follow the restrictions in inclusion criteria 4 are not allowed in the study. Male/female patients who plan to conceive during the time course of the study and
6 months post last infusion of AIN457 are not eligible.
2. Participation in any clinical trial using investigational drug within 4 weeks prior to initial dosing or five half lives of the IMP, whichever is longer and for any other limitation of participation based on local regulations.
3. For patients who were previously treated with TNF blockers, the washout
periods will be required for these patients to be eligble to participate in the trial.
- 6-month washout period prior to baseline for alefacept.
- 3-month washout period prior to baseline for adalimumab and cerolizumab.
- 2-month washout period for baseline for etanercept or infliximab.
4. a) For patients who were previously treated with immunosuppressive agenst other than methotrexate (MTX), sulphasalazine (SSZ) and systemic corticosteriods, a 1 month washout period prior to baseline is required. Immunosuppressive agent include but are not limited to cyclosporine, mycophenolate, trocrolimus and 5-aminosalicylic acid (5-ASA).
- Prednisone should be kept at a stable dose 4 weeks before baseline and throughout the study and not exceed 10mg/day.
- MTX should be kept at a stable dose 4 weeks before baseline and throughout the study and not exceed 25mg/week.
- SSZ should be kept at a stable dose 4 weeks before baseline and throughout the study.
In case of previous leflunomide treatment, a wash out with oral cholestyramine might be considered as an alternative wash out procedure to increase the elimination of leflunomide. Based on the notion that cholestyramine reduces plasma levels of the active leflunomide metabolite by approximately 40% in 24 hours and by 49% in 48 hours, cholestyramine is to be given orally at a dose of 8 g t.i.d. daily for 10 days. The patient may then be dosed with study drug not earlier than 2 weeks after start of the cholestyramine wash out procedure.
4. b) Patients who are on NSAIDS should be kept at a stable dose 4 weeks before baseline and throughout the study.
5. Positive HIV: ELISA and Western blot test result, HBsAg or Hepatitis C test result.
Any active systemic infection within the past 2 weeks including a positive chest X-ray.
6. Current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic,
hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral,
psychiatric, chronic inflammatory diseases with the exception of psoriatic arthritis or other disease which in the clinical judgment of the investigator would make the patient unsuitable for the trial.
7. Liver disease or liver injury as indicated by abnormal liver function tests such as SGOT (AST), SGPT (ALT), ?-GGT, alkaline phosphatase, or serum bilirubin. The Investigator should be guided by the criteria specified in the protocol.
8. Subjects with active or history of clinically significant cardiac abnormalities as specified in the protocol.
9. History of renal trauma, glomerulonephritis, or patient with one kidney.
10. History of malignancy (other than basal cell carcinoma or adequately treated carcinomain-situ of the cervix).
11. Unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access to veins.
12. Conditions asso

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Ankylosing Spondylitis (AS), which belongs to seronegative spondyloarthropathies (SpA).
MedDRA version: 9.1 Level: LLT Classification code 10002556 Term: Ankylosing spondylitis

Intervention(s)

Product Name: AIN457
Product Code: AIN457
Pharmaceutical Form: Powder for solution for infusion
Current Sponsor code: AIN457
Other descriptive name: Recombinant human monoclonal antibody to Il-17 of the IgG1-k-class
Concentration unit: mg/l milligram(s)/litre
Concentration type: up to
Concentration number: 50-
Pharmaceutical form of the placebo: Powder for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: Part 1: Evaluate efficacy of AIN457 at 6 weeks based on the proportion of patients achieving an ASAS20 response
Part 2: To Evaluate the efficacy of lower doses of AIN457 at 6 weeks based on the change in BASDAI response.

Primary end point(s): Part 1: Proportion of ASAS20 responders at week 6 .
Part 2: Change in BASDAI response at week 6.

Secondary Objective: Evaluate proportion of patients achieving an ASAS20 response at other time points
Evaluate proportion of patients achieving an ASAS40 response
Evaluate proportion of patients achieving an ASAS 5/6 response
Part 1 only: Evaluate response to treatment as measured by MRI of the spine
Assess PK of AIN457 in ankylosing spondylitis patients
Assess safety and tolerability of AIN457 in ankylosing spondylitis patients
Assess effect of AIN457 on levels of total IL-17 in ankylosing spondylitis patients
Assess change in BASMI scores (cervical rotation, maximal intermalleolar distance, lumbar lateral flexion, modified Schober index, tragus-to-wall distance)
Assess change in ASAS core set (domains 1-6) as a continuous outcome measure
Assess change in BASDAI and physician global assessment
Assess HRQoL by using the Medical Outcome Short Form (36), Health Survey SF-36®, and (ASQoL).
Assess the change in Maastricht Ankylosing Spondylitis Enthesis Score (MASES) and Leeds enthesis index (LEI)

Secondary ID(s)

CAIN457A2209

not available