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-IL17 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-AT
• Date of registration: 31/03/2009
• 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-IL17 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-IL17 monoclonal antibody) in patients with moderate to severe active Crohn’s disease - A2202
• Date of first enrolment: 07/05/2009
• 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. Patients with active disease despite prior treatment with corticosteroids for at least 2 weeks, or immunosuppressants for at least 3 months. Patients who are being 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 dose of prednisolone not exceeding 40 mg for two weeks prior to baseline.
Patients who are being treated with immunosuppressants other than those listed above, such as cyclosporine, tacrolimus and mycophenolate, are not eligible. These subjects will be required to stop immunosuppressants 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 +ve 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.These subjects will be eligible to participate if – according to local guidelines – latent tuberculosis can be excluded. For sites using QuantiFeron test, a +ve test at screening will exclude subject. If the result for either PPD or QuantiFeron test is indeterminate, subject will be excluded

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

6a Concomitant treatment w anti-TNF-a therapy (or other biological therapy), and systemic immunosuppressive agents, e.g. cyclosporine, mycophenolate, pimecrolimus, or tacrolimus, except azathioprine, its metabolite 6-MP and MTX. The following washout period will be required for such subjects to be eligible to participate in the trial.
- 3 mo washout prior to baseline (WPB) for certolizumab
- 2 mo WPB for adalimumab, etanercept and infliximab
- 1 mo WPB for cyclosporine, mycophenolate, pimecrolimus, tacrolimus, and any other systemic immunosuppressants not listed under exclusion criterion #7b
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 baseline and throughout the whole study period.

7 Prior therapy w rituximab

8 Corticosteroids dose equivalent to >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/ family history) or w 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 w significant and persistent LVEV dysfunction (< 40%) • History (3 mo) of significant, persistent arrhythmias e.g. ventricular fibrillation, tachycardia, atrial fibrillation, flutter
• Symptomatic coronary artery disease • Presence of severe cardiac disease (NYHA Class = III) and/or abnormal ECG - 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 at least prior to enrollment / randomization, to rule out lab error
• If total bilirubin conc. increased > 2xULN, total bilirubin to be differentiated into direct and indirect reacting bilirubin. Serum bilirubin should not exceed value of 1.6 mg/dL (27 µmol/L). Recheck results must be within normal limits

13 Total WBC count outside 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, demyelinating disease

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

16Administration of live vaccines within 6 mo prior to dosing

17 History of immunodeficiency diseases,

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 =450)
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
Pharmaceutical form of the placebo: Powder for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

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).

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

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)

not available

CAIN457A2202