E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe Crohn's disease (CD) |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study is exploratory in nature, therefore, no formal hypothesis testing is planned. The study objectives are: 1. To evaluate the safety and tolerability and determine the highest tolerable dose of laquinimod (up to 2mg/day), in subjects with active moderate to severe CD 2. To evaluate the clinical effect and dose response of laquinimod (0.5-2mg/day), in subjects with active moderate to severe CD
|
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The following two sub-studies are fully described in the same Sponsor' protocol CD-LAQ-201:
1. Pharmacokinetic ancillary study (PK):
Blood samples for PK analysis - 24h profile - will be collected from subjects in the first cohort (0.5 mg/placebo) on week 4.
A single, pre-dose sample will be collected from the first cohort (0.5 mg/placebo) on week 1 as part of steady state course assessment.
(This study is an ancillary study to be performed in subset of sites).
2. Voluntary participation in a pharmakogenetic sub-study:
A single sample of approximately 6ml (about 1 teaspoon) of blood will be collected only once during the study.
The objective of this pharmacogenetic study is to collect and store DNA samples for use in future exploratory analyses for the assessment of possible associations between genetic polymorphisms and response to laquinimod.
|
|
E.3 | Principal inclusion criteria |
Subjects must meet all the inclusion criteria to be eligible:
1.Males and females 18-65 years old (inclusive). 2.Subjects diagnosed with Crohn’s disease for at least 3 months, 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
|
|
E.4 | Principal exclusion criteria |
Any of the following will exclude the subject from entering the study: 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). 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, as determined by medical history, physical examinations, ECG, laboratory tests or imaging. 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 12.Subjects with history of any malignancy in the last year, 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 screening 14.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. 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. 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). 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 acceptable method of birth control. 26.A known drug hypersensitivity that would preclude administration of laquinimod, such as hypersensitivity to: mannitol, meglumine or sodium stearyl fumarate. 27.Subjects unable to comply with the planned schedule of study visits and study procedures.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
This study is exploratory in nature, therefore, no formal hypothesis testing is planned. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The study will be completed upon completion of the 4 weeks follow up period (following 8 weeks of treatment). |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |