Patients with ulcerative colitis (UC) according to European Crohn's and Colitis Organisation (ECCO) consensus
Conditions
Interventions
Product Name: LT-02 (modified-release PC pellets)
Product Code: LT-02
Pharmaceutical Form: Granules for oral suspension
INN or Proposed INN: Modified-release phosphatidylcholine
Concentration unit: g
Sponsors
Lipid Therapeutics GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Men and women =18 years who have given written Informed Consent, 2) Patients with proven UC (according to ECCO consensus definition [24]: UC is a chronic continuous mucosal inflammation of the colon without granulomas on biopsy, affecting the rectum and variable extent of the colon in continuity, which is characterized by a relapsing and remitting course. The diagnoses should be established by a combination of medical history, clinical evalution, and typical endoscopic and histologic findings: a) Medical history and clinical features: loose stools [>6 weeks], episodes of bloody stools and stool urgency, episodes of relapse and periods of remission or an unremitting, continuous course over months; exclusion of infectious colitis [microbiological testing, including Clostridium difficile toxin A and B, Campylobacter spp., E. coli 0157:H7; depending on the medical history fresh, warm stool samples should be tested for amoebae or other parasites], exclusion of drug-induced forms of colitis, b) Endoscopic features, including a colonoscopy with intubation of the terminal ileum: inflammation of the rectum, continuous inflammation to more proximal parts, usually clear demarcation between inflamed and normal areas. Signs of inflammation are vascular congestion or reduction of visible vascular patterns, as well as mucosal friability [after contact with the endoscope]. Moreover, a coarse granular appearance, mucosal erosions or ulcerations may occur, c) Histologic features from multiple mucosal biopsies: absence of granulomas, architectural features [crypt branching, crypt distortion, crypt atrophy or surface irregularity], epithelial cell abnormalities [mucin depletion, Paneth cell metaplasia] and inflammatory signs [increased lamina propria cellularity, basal plasmacytosis, basal lymphoid aggregates, lamina propria eosinophils], Patients may be included into the study if clinician, endoscopist [may be identical with clinician] and pathologist state that the found features are compatible with the diagnosis of UC), 3) Patients naïve to any form of controlled release PC treatment, 4) Active disease course for the last 6 weeks or longer with bloody diarrhea (anamnestic mean number of bloody stool per day =4), 5) SCCAI =5 and SCCAI subscore for “blood in stool” =2 at Baseline Visit (V2), (SCCAI and subscore for blood are calculated as the rounded mean over the last 7 days), 6) Patients with an inadequate response to a treatment with =3g of mesalazine per day, over a period of 4 weeks or a documented intolerance to mesalazine, 7) Other drugs for the treatment of UC are allowed, under the following circumstances: - Systemic acting oral steroids are allowed if taken for =8 weeks prior to start of the study with a stable dose for =4 weeks prior to start of the study, - Immunosuppressive therapy with azathioprine (2-2.5 mg/kg) or 6- mercaptopurine (1-1.5 mg/kg) is allowed, if taken for =3 months prior to start of the study, 8) Ability of the patient to understand character and individual consequences of the clinical study, 9) Special requirements for women of childbearing potential: - Negative pregnancy test at V1 and V2, - Use of one highly effective method of contraception for the entire duration
Exclusion criteria
Exclusion criteria: 1) Toxic megacolon or fulminant colitis, 2) a) Therapy with cyclosporine, tacrolimus, methotrexate, or tumor necrosis- (TNF)-alpha-antagonists within 3 months prior to study entry, b) Current treatment with opiates or loperamide, c) Current antibiotic treatment, 3) Rectal applications of aminosalicylates, budesonide, or other steroids within 4 weeks prior to study entry, 4) Oral application of topically acting steroids, e.g. budesonide, within 4 weeks prior to study start, 5) Treatment with other IMP within 3 months prior to study entry, 6) Condition after complete or partial resection of the colon, 7) Infectious colitis, including cytomegalovirus or Clostridium difficile induced colitis, 8) Crohn’s disease, 9) Colitis due to other reasons than UC like known diverticulitis, radiation colitis, ischemic colitis, microscopic colitis, or indeterminate colitis, 10) Malabsorption syndromes, chronic pancreatitis, 11) Celiac disease, 12) Acute bleeding hemorrhoids, 13) Other inflammatory or bleeding disorders of the gastrointestinal tract, or diseases that may cause diarrhea or gastrointestinal bleeding, 14) Pregnant or nursing women, 15) Known drug, alcohol, or medication abuse during the last 2 years prior to start of the study, 16) Any other uncontrolled systemic diseases (e.g. cardiac, renal, pulmonary, or hepatic) or severe chronic diseases (e.g. malignant tumor, HIV infection, high-grade intraepithelial neoplasia), 17) Ulcerative proctitis with a disease extent <10 cm, 18) Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial. For all patients included in Lithuania, the following criterion is added as exclusion criterion no. 2: “No current treatment for UC with either high-dose 5-ASA (at least 3g/d) or oral steroids or immunosuppressants or combinations.” Please note that due to this insertion, the numbering of the subsequent exclusion criteria is shifted in Lithuania (i.e. former criterion no. 2 is changed to no. 3, former no. 3 is changed to no. 4 etc.).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the efficacy and safety of modified-release PC (LT-02) in mesalazine-refractory UC.;Secondary Objective: The secondary objective is to determine the optimal dose of modified-release PC (LT-02) in mesalazine-refractory UC.;Primary end point(s): Mean rounded SCCAI change from baseline (V2) to Week 12 (V5) or last assessment during the double-blind treatment period. | — |
Countries
Germany, Lithuania
Outcome results
None listed