A Phase IIa, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Sequential Cohorts, Dose Range Finding Study to Evaluate the Safety, Tolerability and Clinical Effect of Escalating Doses of Laquinimod in Active Moderate to Severe Crohn?s Disease - ND

• Conditions: Crohn Disease; MedDRA version: 9.1Level: LLTClassification code 10011401Term: Crohn's disease; MedDRA version: 9.1Level: LLTClassification code 10013099Term: Disease Crohns

• Registration Number: EUCTR2008-004276-49-IT
• Lead Sponsor: Teva Pharmaceutical Industries Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-08-04
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1.Males and females 18-65 years old (inclusive).
2.Subjects diagnosed with Crohn?s disease for at least 3 months prior to screening, which has been appropriately documented and supported by endoscopy or radiology (performed within 36 months prior to screening and after surgical resection), or surgery
3.Moderate to severe Crohn's disease patients as determined by a CDAI score of 220-450 (inclusive).
4.Subjects with CRP levels above 5 mg/L.
5.Subjects willing and able to provide 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) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Subjects with a diagnosis of Indeterminate Colitis.2.Subjects with positive results on stool culture for enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter and Clostridia Difficile toxin assay), at screening.3.Subjects who have had bowel surgery within the 3 months prior to screening or with planned elective surgery or hospitalization during the course of the study (that may interfere with study compliance or outcome)4.Subjects with clinically significant Short Bowel Syndrome.5.Subjects with clinically significant GI obstructive symptoms.
6.Subjects with intra-abdominal abscess.7.Subjects with fistula with clinical or radiological evidence of abscess.8.Subjects with ileostomy, colostomy or who receive parenteral nutrition.9.Subjects with a clinically significant or unstable medical or surgical condition that, in the Investigator?s opinion, would preclude safe and complete study participation, 10.Subjects with a ≥2x upper limit of normal (ULN) serum elevation of either of the following at screening: ALT, AST, GGT, ALKP or direct bilirubin.
11.A QTc interval which is  500 msec (according to machine output), obtained from:Two ECG recordings at screening visitORThe mean value calculated from 2 baseline ECG recordings 12.Subjects with history of any malignancy in the last year, prior to screening, excluding basal cell carcinoma. 13.Subjects treated with oral corticosteroids (e.g prednisolone/budesonide), who have initiated this treatment within less than 4 weeks prior to creening14.Subjects treated with more than 20mg/day of prednisolone (or equivalent) or budesonide > 6mg/day for CD at screening, or whose corticosteroid dosage regimen is not stable for at least 2 weeks prior to screening. [Stable dose defined as ≤ 2.5mg prednisolone (or equivalent) increase or decrease, no change in budesonide and no IV or IM steroid administration, within the last 2 weeks]15.Subjects treated with 5-ASA who are not on stable dose for at least 2 weeks prior to screening.
16.Subjects treated with antibiotics for CD who are not on a stable dose for at least 4 weeks prior to screening.17.Subjects treated with 6-MP, AZA or MTX, who have initiated this treatment within 12 weeks prior to screening or who are not on a stable dose for at least 6 weeks prior to screening.18.Subjects treated with Anti-TNFs within 8 weeks prior to screening. [The percentage of subjects previously treated with anti TNF drugs will be limited to approximately 40% of subjects randomized for each cohort. All site principle investigators will be notified by the Sponsor when the quota of previous treatment with anti-TNF drugs has been reached for each cohort. see Section ‎12.2 of the protocol]19.Subjects treated with cyclosporine, tacrolimus, mycophenolate mofetil or thalidomide within 2 months prior to screening
20.Subjects treated with natalizumab within 6 months prior to screening
21.Subjects who have used any other investigational drugs within 3 months prior to screening.22.Use of inhibitors of CYP3A4 within 2 weeks prior to baseline visit (1 month for fluoxetine, see Appendix 4).
23.Use of amiodarone within 2 years prior to screening visit
24.Women who are pregnant or nursing at the time of screening, or who intend to be during the study period.
25.Women of child-bearing potential who do not practice an accep

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety and tolerability and determine the highest tolerable dose of laquinimod (up to 2 mg/day), in subjects with active moderate to severe CD;Secondary Objective: To evaluate the clinical effect and dose response of laquinimod (0.5-2 mg/day), in subjects with active moderate to severe CD.;Primary end point(s): This study is exploratory in nature, therefore, no formal hypothesis testing is planned.