Active Ulcerative Colitis MedDRA version: 14.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: PEG-liposomal prednisolone sodium phosphate
Product Code: Nanocort
Pharmaceutical Form: Concentrate and diluent for solution for infusion
INN or Proposed INN: Prednisolone Sodium Phospha
Sponsors
Enceladus Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female = 18 to 75 years of age. 2. Documented history of UC (at least 6 months) as assessed by endoscopy and confirmed by histological measurements with a minimal disease extent of 15 cm from the anal verge and a minimal period of active disease of 14 days. 3. Negative stool culture for enteric pathogens, including Clostridium difficile, ova and parasites. 4. Mayo score = 5 with endoscopic sub-score of = 2 and rectal bleeding sub-score =1. 5. Medication: 6-MP/azathioprine, MTX receiving for at least 12 weeks and stable dose for > 4 weeks or discontinued for > 4 weeks; rectal medications stopped for > 4 weeks, 5-ASA stable or stopped for > 2 weeks. If receiving cyclosporine or biologics (e.g. TNF alpha-blocker), these medications should be continued at the same dose for at least two cycles after Day 1. A cycle commonly takes 8 weeks, but may be shorter in the individual subjects, when loss of response has been encountered previously and the dosing interval has been adjusted. 6. In good physical and mental health (other than the disease under study) as determined by medical history and physical examination. 7. The results of the following laboratory tests at screening must be as specified below: a. Hemoglobin = 8.5 g/dL (International System of Units [SI]: = 85 g/L) b. White blood cells (WBC) = 3.0 x 10E3 cells/mm3 (SI: = 3.0 x10E9 cells/L) c. Neutrophils = 1.5 x 10E3 cells/mm3 (SI: = 1.5 x10E9 cells/L) d. Platelets = 100 x 10E3 cells/mm3 (SI: = 100 x10E9 cells/L) e. Serum ALT = 1.5 x upper limit of normal (ULN) f. Total bilirubin level = 1.25 x ULN g. Creatinine clearance = 80 mL/min using the Cockcroft formula 8. Female subjects must have a negative blood pregnancy test, unless they are surgically sterile, had a hysterectomy or have been post-menopausal for at least 1 year (at least 12 consecutive months without menses). 9. Women of childbearing potential must use a medically acceptable means of birth control and agree to continue its use during the study and for at least 12 weeks after the last dose of study drug. Medically acceptable forms of birth control include oral contraceptives, injectable or implantable methods, intrauterine devices, tubal ligation (if performed more than 1 year before screening), or double-barrier contraception. Sexually active men must agree to use a medically acceptable form of contraception during the study and continue for at least 12 weeks after the last dose of study drug. 10. Able and willing to give voluntary written informed consent and agree to schedule of assessments. 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 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Treatment with local or oral corticosteroids within 4 weeks before screening or with intra articular or intramuscular corticosteroids within 8 weeks before screening. If non-systemic steroids are being used for other chronic inflammatory conditions, subjects may be included at the discretion of the Investigator after discussion with the medical monitor. 2. Severe colitis, defined as a bloody stool frequency of more than six per day with any one of tachycardia (pulse > 90 beats/min), temperature (> 37.8 degrees C), anaemia (haemoglobin 30 mm/h), 3. Intolerance of or unresponsiveness to corticosteroids, especially a history of steroid psychosis. 4. A history of significant psychological, neurologic, renal, gastrointestinal (other than UC), or metabolic disease (diabetes mellitus). 5. A history of clinically severe or unstable medical condition involving cardiac, pulmonary, liver or endocrine disorders. 6. Any concurrent illness, disability or clinically significant abnormality (including laboratory tests) that may affect the interpretation of clinical safety or efficacy data or prevent the subject from safely completing the assessments required by the protocol as judged by the Investigator. 7. Stoma, proctocolectomy or total colectomy or imminent need for surgery. 8. Concurrent bowel and intestine malignancy or a history of cancer (other than basal cell carcinoma or cervical carcinoma successfully treated more than 5 years prior to screening). 9. Subjects with, other bleeding, infectious, ischemic, or immunological diseases with or without gastrointestinal involvement. 10. Be currently pregnant or breastfeeding or not willing to maintain birth control methods for at least 12 weeks after last study medication administration. 11. Medical, psychiatric, cognitive, or other conditions that, according to investigator’s medical judgment, compromise the subject's ability to understand the subject information, to give informed consent, to comply with the requirements of the study protocol (that is likely to affect the subject’s return for visits on schedule), or ability to complete the study. 12. Participation in another experimental therapy study within 90 days prior to screening for this study or current enrollment in any other study with investigational drugs or device. 13. Positive serology for human immunodeficiency virus (HIV) 1 or 2 or hepatitis B or C, or any history of hepatitis from any cause with the exception of hepatitis A.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety of PEG-liposomal prednisolone sodium phosphate (Nanocort) ;Secondary Objective: • To explore the efficacy of PEG-liposomal prednisolone sodium phosphate (Nanocort) • To evaluate the pharmacokinetics of free prednisolone and prednisolone phosphate in the plasma. ;Primary end point(s): • Frequency of Serious adverse events in Nanocort versus placebo group • Frequency of Adverse events in Nanocort versus placebo group • Changes in clinical status, vital signs and laboratory parameters over the duration of the study in Nanocort versus placebo group. ;Timepoint(s) of evaluation of this end point: Day 2 and 15 of treatment. Day 29, 57 and 87 after treatment period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Percentage of subjects achieving clinical remission at Day 29 as measured by Mayo score in Nanocort versus placebo group. • Percentage of subjects achieving clinical remission at Day 15, 29, 57 and 85 as measured by partial Mayo score in Nanocort versus placebo group. • Percentage of subjects achieving clinical response at Day 15, 29, 57 and 85 as measured by partial Mayo score in Nanocort versus placebo group. • Percentage of subjects maintaining a clinical response in Nanocort versus placebo group, in subjects having previously achieved a clinical response after baseline evaluations. • Scoring the histopathological assessments on biopsies by microscopic evaluation (acute inflammation score and grading scale of inflammation) in Nanocort versus placebo group. • Free prednisolone and liposomal prednisolone phosphate levels in the plasma at Day 1, 15, 29 and 57 in the Nanocort versus placebo group. ;Timepoint(s) of evaluation of this end point: At day 15, 29, 57 and 85 | — |
Countries
Belgium, Netherlands
Contacts
Public ContactDr. Herma H. Fidder
UMC Utrecht
Outcome results
None listed