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

• Register: EUCTR
• Last refreshed on: 18 October 2021
• Main ID: EUCTR2008-004276-49-FR
• Date of registration: 21/07/2008
• Prospective Registration: Yes
• Primary sponsor: Teva Pharmaceutical Industries Ltd.
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 18/12/2008
• Target sample size: 199
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004276-49
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Sequential cohort design; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; 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

Belgium, France, Italy, Netherlands, Spain, United Kingdom

Key inclusion & exclusion criteria

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

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:
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.




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

Health Condition(s) or Problem(s) studied

Moderate to severe Crohn's disease (CD)
MedDRA version: 9.1 Level: PT Classification code 10011401 Term: Crohn's disease

Intervention(s)

Product Name: Laquinimod Capsules 0.5 mg
Product Code: TV-5600
Pharmaceutical Form: Capsule*
INN or Proposed INN: laquinimod
CAS Number: 248282-07-7
Current Sponsor code: TV-5600
Other descriptive name: ABR-215062 sodium salt
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 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

Primary end point(s): This study is exploratory in nature, therefore, no formal hypothesis testing is planned.

Secondary Objective: -

Secondary ID(s)

2008-004276-49-ES

CD-LAQ-201

Ethics review

Status: Approved
Approval date: 18/12/2008
Contact:

Results

• Results available: Yes
• Date Posted: 28/12/2016
• Date Completed: 24/11/2011
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-004276-49/results