An open-label non-randomized extension study to evaluate the safety and tolerability of AIN457 (anti interleukin-17 monoclonal antibody) in patients with moderate to severe ankylosing spondylitis - A2209E1

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2009-011591-30-GB
• Date of registration: 20/10/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: An open-label non-randomized extension study to evaluate the safety and tolerability of AIN457 (anti interleukin-17 monoclonal antibody) in patients with moderate to severe ankylosing spondylitis - A2209E1
• Scientific title: An open-label non-randomized extension study to evaluate the safety and tolerability of AIN457 (anti interleukin-17 monoclonal antibody) in patients with moderate to severe ankylosing spondylitis - A2209E1
• Date of first enrolment: 21/09/2010
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011591-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Netherlands, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients who participate and complete the core CAIN457A2209 study up to and including the EoS i.e. Visit 16 (Week 24), may enter the extension study upon signing informed consent.

2. Patients who discontinued the core study due to unsatisfactory therapeutic effect at their Visit 14 (Week 16) or later may enter the extension study within three weeks of completing the study discontinuation visit of the core study, provided that at their discontinuation visit they meet the criteria below, Patients who do not enter the extension study within 3 weeks after completing the study discontinuation visit of the core study, will have an additional baseline visit (visit 18) and must meet the criteria below.
a. There is no improvement (compared with the core study baseline) in two out of the
following four domains: patient global assessment, pain, BASFI and the mean of the
two morning stiffness questions from the BASDAI
OR
b. There is a deterioration (compared with the core study baseline) in one of the four
domains (deterioration defined as >=20% worsening and an absolute worsening of
>=1 unit)

3. Women of childbearing potential must be using simultaneously double-barrier or two highly effective methods of contraception, (e.g. intra-uterine device plus condom,
diaphragm plus condom, etc; hormone replacement as either oral or implantable is
acceptable as one form), from the time of screening for the duration of the entire study, up to study completion and up to 16 weeks post last drug administration. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

4. Male patients willing to use simultaneously two highly effective methods of contraception (e.g. intra-uterine device plus condom) for the duration of the entire study, up to study completion visit and up to 16 weeks post the last drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception.
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) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Patients for whom continued treatment with AIN457 in the extension is not considered appropriate by the treating physician.

2. Patients who were non-compliant or who demonstrated a major protocol deviation in the core CAIN457A2209 study.

3. Patients who discontinued from the core CAIN457A2209 study before Visit 14
(Week 16).

4. Female patients who are pregnant or lactating

5. Any active systemic infection within the past 2 weeks including a positive chest X-ray.

6. Positive human immunodeficient virus (HIV: ELISA and Western blot) test result,
Hepatitis B surface antigen (HBsAg) or Hepatitis C test result, where patients have been re-tested.

The following Exclusion Criteria as defined in the core trial [CAIN457A2209] will continue to be valid with minor revisions:

7. Positive Purified Protein Derivative (PPD) tuberculin skin test of = 5 mm at baseline, (where patients have been re-tested). A positive PPD test will be defined using the MMWR 2000 guidance, summarized as criteria for tuberculin positivity by risk group. A PPD test should not be done in subjects who had a tuberculosis vaccination in the past. These subjects will be eligible to participate if – according to local guidelines – latent tuberculosis can be excluded. For those study sites using QuantiFeron test a positive test at baseline (where patients have been re-tested) will exclude the subject from the participation in the study. If the result for either PPD or QuantiFeron test is indeterminate the subject will be excluded.

8. For previous use of immunosuppressive agents a wash-out period of at least 1 month or 5 half-lives, whatever is longer, is required. Immunosuppressive agent include but are not limited to cyclosporine, mycophenolate, tacrolimus, and 5-aminosalicylic acid (5-ASA).

If on previous treatment with anti-TNF-a therapy (or other biological therapy), the
following washout periods will be required for such patients to be eligible to participate in the trial.
• Six (6)-months wash out prior to dosing for alefacept, rituxan and raptiva,
• Three (3)-months washout prior to baseline for adalimumab and certolizumab,
• Two (2)-months washout prior to baseline for etanercept and infliximab,
• One (1) month washout prior to baseline for systemic immunosuppressants including, but not limited to azathioprine, cyclosporine, and leflunomide.

Patients on concomitant prednisone, methotrexate (MTX) or SSZ can be included,
whereby:
• Prednisone should be kept at a stable dose 4 weeks before baseline and throughout the
study and not exceed 10 mg/day.
• MTX should be kept at a stable dose 4 weeks before baseline and throughout the
study and not exceed 25 mg/week.
• SSZ should be kept at a stable dose 4 weeks before baseline and throughout the study.

9. Patients who are on NSAIDS should be kept at a stable dose 4 weeks before baseline and throughout the study.


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: 12.0 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 milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Secondary Objective: To assess the immunogenicity of AIN457

To assess the total IL-17 concentration in blood at steady-state

To assess the pharmacokinetics of AIN457 at steady state

Main Objective: To assess the safety and tolerability of AIN457 in patients with moderate to severe ankylosing spondylitis receiving i.v. AIN457 initially up to 6 months (part1) with a possible extension of a further 6 months (part2) in patients who participated in the core CAIN457A2209 phase II proof-of-concept study

Primary end point(s): Safety and tolerability.

Secondary ID(s)

CAIN457A2209E1

not available

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 15/12/2016
• Date Completed: 05/12/2012
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011591-30/results