A multicenter, randomised, double-blind, placebo-controlled, parallel-group proof-of-concept study to assess the efficacy, safety and tolerability of two single i.v. infusions of AIN457 10 mg/kg (anti IL-17 monoclonal antibody) in patients with moderate to severe active Crohn's disease - A2202

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-008359-40-DE
• Date of registration: 23/06/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A multicenter, randomised, double-blind, placebo-controlled, parallel-group proof-of-concept study to assess the efficacy, safety and tolerability of two single i.v. infusions of AIN457 10 mg/kg (anti IL-17 monoclonal antibody) in patients with moderate to severe active Crohn's disease - A2202
• Scientific title: A multicenter, randomised, double-blind, placebo-controlled, parallel-group proof-of-concept study to assess the efficacy, safety and tolerability of two single i.v. infusions of AIN457 10 mg/kg (anti IL-17 monoclonal antibody) in patients with moderate to severe active Crohn's disease - A2202
• Date of first enrolment: 08/09/2009
• Target sample size: 72
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-008359-40
• 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

Austria, Germany, Poland

Key inclusion & exclusion criteria

Inclusion criteria:
1.
Male or female; 18-75 years old

2.
Females must have negative pregnancy test results at screening and baseline. WoCBP must be using simultaneously double-barrier or two acceptable methods of contraception from the time of screening and for the duration of the study, through study completion and for 4 months following study completion. Periodic abstinence and withdrawal are not acceptable methods of contraception. Postmenopausal females must have had no regular menstrual bleeding for at least 2 years prior to initial dosing. If menopause is confirmed by serum FSH level of >40 IU/L at screening, pregnancy test will be required only at screening. Female subjects who report surgical sterilization must have had the procedure at least 6 months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and/or PI 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 6 months prior to first dosing.

3.
Male subjects willing to use simultaneously two acceptable methods of contraception (e.g. spermicidal gel plus condom) for entire duration of the study, up to the study completion visit and at least for 6 months following the completion of the study. Periodic abstinence and withdrawal are not acceptable methods of contraception.

4.
Diagnosis of CD for at least 3 months prior to screening.

5.
Confirmation of CD by endoscopic or imaging examination.

6.
Moderate to severe active CD at baseline, defined as: CDAI =220 and =450 Note: Baseline CRP values may be either within normal limits or elevated. However, not more than 50% of all patients included in the trial should belong to the subgroup of patients with normal CRP values. The upper limit of normal (ULN) for serum CRP is defined as =10mg/L (=1mg/dl)

7.
Active disease despite prior treatment with corticosteroids for at least 2 weeks, or immunosuppressants for at least 3 months.
Patients treated with azathioprine, 6-MP or MTX are eligible but must have been on a stable dose for at least 10 weeks prior to baseline.
Patients treated with corticosteroids are eligible but must have been on a stable doses of prednisone not exceeding 40 mg for two weeks prior to baseline.
Patients treated with immunosuppressants other than those listed above, such as cyclosporine, tacrolimus and mycophenolate, are not eligible. These subjects will be
required to stop immunosuppressant (except limited dose corticosteroids) prior to baseline. These patients are eligible after observing a wash out period as specified in Exclusion criterion #7.

8.
Absence of clinically relevant abnormalities for screening laboratory test results.

9.
Able to communicate well with the investigator, and to understand and comply with the requirements of the study.

10.
Understand and sign the written informed consent.
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.
BMI > 34.

2.
Positive PPD tuberculin skin test (= 5 mm) at or 6 mo prior screening (MMWR 2000). PPD test not to be done in subjects who had a TB vaccination. For sites using QuantiFeron test, a positive test at screening will exclude subject also if the result for either PPD or QuantiFeron test is indeterminate.

3.
Active bowel structuring disease and pre-stenotic dilation on radiography.

4.
Fistulizing disease complicated by sepsis and/or untreated abscess.

5.
Multiple bowel surgeries/clinically important short bowel syndrome.

6.
a. Concomitant treatment with anti-TNF-a therapy (or other biological therapy) and systemic immunosuppressive agents such as cyclosporine, mycophenolate, pimecrolimus, or tacrolimus, except azathioprine, its metabolite 6-MP and MTX.
b. Patients who are being treated with azathioprine, 6-MP and MTX are eligible but must have been on a stable dose for at least 10 weeks prior to baselina and throughout the whole study period.

7.
Prior therapy with rituximab.

8.
Corticosteroids dose equivalent to a >40mg dose of prednisone/day.

9.
Subjects demonstrating clinical improvement due to other CD therapy.

10.
Symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, GI, endocrine, pulmonary, cardiac, neurologic, cerebral, psychiatric, or other disease.

11.
Active or history of clinically significant cardiac abnormalities, e.g. • Requiring QT-prolonging drugs • QTc >450msec, long QT-syndrome (own or family history) or with family history of sudden unexplained death • LBBB or subjects who have been hospitalized for heart failure of cardiac etiology in previous 6 mo, and subjects who have significant and persistent LVEV dysfunction (< 40%) • History of, in the preceding 3 mo, significant and persistent arrhythmias such as ventricular fibrillation or tachycardia, or atrial fibrillation or flutter • Symptomatic coronary artery disease • Presence of severe cardiac disease (NYHA Classification = III) and/or an abnormal ECG and considered by the investigator unsafe for the study.

12.
Liver disease/injury indicated by SGOT (AST), SGPT (ALT), ?-GGT, alkaline phosphatase, or serum bilirubin, guided by following criteria • Any single parameter may not exceed 2xULN. A single parameter elevated up to and including 2xULN to be re-checked once more asap, and in all cases, at least prior to enrollment /randomization, to rule out lab error • If the total bilirubin concentration is increased above 2xULN, total bilirubin to be differentiated into the direct and indirect reacting bilirubin. Serum bilirubin should not exceed the value of 1.6 mg/dL (27 µmol/L). Re-check results must be within normal limits (or returning to within normal limits).

13.
Total WBC count outside the range of 4500–13,000/µl, or platelets <100,000/µl at screening.

14.
History of severe hypersensitivity to any biological, including serious allergic reaction, lupus-like syndrome, or demyelinating disease.

15.
Donation/loss of 400 mL or more of blood within 8 weeks prior to dosing or longer if required by local regulation.

16.
Administration of live vaccines within 6 mo prior to dosing.

17.
History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.

18.
A positive Hep B surface antigen (HBsAg) or Hep C test result.

19.
Significant illness within the two weeks prior to dosing or any active systemic infection or medical condition that may require treatment or therapeutic intervention dur

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

Health Condition(s) or Problem(s) studied

Moderate to severe Crohn's disease (CDAI >/= 220 and MedDRA version: 9.1 Level: LLT Classification code 10011401 Term: Crohn's disease

Intervention(s)

Product Name: AIN457
Product Code: AIN457
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: not available
CAS Number: not availabl
Current Sponsor code: AIN457
Other descriptive name: rhumAb to Il-17A (IgG1-k-class)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 47-
Pharmaceutical form of the placebo: Powder for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: Efficacy of AIN457 at 6 weeks on mean CDAI

Primary end point(s): A Bayesian approach will be adopted to assess the efficacy as measured by the change from baseline in the CDAI 6 weeks after infusion 1, that is, at visit 8 (primary endpoint and analysis).

Secondary Objective: % of subjects achieving remission and/or response, as defined by CDAI <150 or a
decrease of at least 70 points from baseline

Effect of AIN457 on mean CDAI at 2 and 4 weeks

Area under CDAI score curve from week 4 to week 10

Maintenance of remission and/or response during f/u period and at the end of study

PK of AIN457

Safety and tolerability of AIN457

Secondary ID(s)

CAIN457A2202

2008-008359-40-AT

not available