Ulcerative colitis
Conditions
Interventions
Product Code: KSP-0243
Pharmaceutical Form: Tablet
INN or Proposed INN: Not Applicable
Other descriptive name: KSP-0243
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration numb
Sponsors
Kissei Pharmaceutical Co., Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male and female outpatients aged 18 to 74 years (inclusive) at the time of informed consent form (ICF) signature. 2.Patients with body mass index between 18 and 35 kg/m2(inclusive). 3.Diagnosis of UC at least 3 months prior to first dose of the study drug on Day 1. 4.Active mild-to-moderate UC defined at screening by the following criteria: a. Endoscopic appearance typical for UC and extending >15 cm from anal verge b. Mayo Score =3 and =10 c. mMES =1 d. Mayo rectal bleeding (RB) subscore (RBS) =1. 5.Evidence of active inflammation at screening by RHI =4 with neutrophils in the epithelium (subscore =1) in sigmoid or rectum. 6.Currently receiving treatment for UC with oral 5-aminosalicylic acid (eg, mesalamine, sulfasalazine) and/or corticosteroids (prednisone [=20 mg/day] or equivalent, budesonide or budesonide multi-matrix [=9 mg/day]) on a stable dose for at least 4 weeks prior to first screening visit, or with azathioprine (=3 mg/kg/day) or 6-mercaptopurine (=2 mg/kg/day) on a stable dose for at least 12 weeks prior to first screening visit. 7.Patients who demonstrated an inadequate response or loss of response to current treatment for UC. 8.Patients who agree to abstain from heterosexual activity, use adequate hormonal contraception, or use highly effective double barrier contraception (ie, a combination of condom or diaphragm AND hormonal contraception associated with inhibition of ovulation, intrauterine device, or intrauterine hormone-releasing system) during the study and for 12 weeks after the last dose of study drug, unless: a. Patient is a female of non-childbearing potential, defined as women who had surgical sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) at least 90 days prior to first screening visit OR postmenopausal women =45 years of age with > 1 year since last menstrual period. b. Patient is a surgically sterilized male through vasectomy or bilateral orchiectomy at least 90 days prior to first screening visit. 9.For women of childbearing potential, a negative serum pregnancy test at first screening visit and a negative urine pregnancy test within 24 hours prior to first dose of the study drug. 10.Patients who understand the study procedures and agree to participate in the study by giving 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Any concurrent clinically significant, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, haematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator might confound study results or pose additional risk to the patient by their participation in the study. 2. Any abnormal finding in physical examination, vital signs, 12-lead ECG, or laboratory assessment at first screening visit considered as clinically significant and that in the opinion of the investigator might pose additional risk to the patient by their participation in the study. 3. Diagnosis of Crohn’s disease, indeterminate colitis, pouchitis, ischemic colitis, microscopic colitis, radiation colitis, diverticular-disease associated colitis, stenosis of the intestine, colostomy, ileostomy, abscesses or toxic megacolon, malabsorption, short bowel syndrome, history of colorectal cancer, colorectal dysplasia (with the exception of dysplasia in polyps which have been removed), extensive mucosal shedding, deep-seated ulcers, or recent colectomy. 4. Concurrent malignancy or prior malignancy within 2 years with the exception of adequately treated nonmelanoma skin cancer, adequately treated cervical cancer, or superficial bladder cancer. 5. Diagnosis or suspected liver function impairment (aspartate aminotransferase or alanine aminotransferase >3 × upper limit of normal). 6. Current bacterial or parasitic pathogenic enteric infection, including treatment for Clostridium difficile infection or other pathogens within 30 days prior to randomization. 7. History of chronic infections, including but not limited to tuberculosis (TB), human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) within 6 months prior to first screening visit. 8. Positive immunological test at screening for TB (QuantiFERON®-TB Gold test), HIV, HCV, and HBV, or positive serological test for syphilis. 9. Any live vaccinations within 30 days prior to first screening visit. 10. Current or recent history of alcohol dependence or illicit drug use. 11. Pregnant or lactating females. 12. Prior use of epoetin alfa. 13. Use of monoclonal antibodies (e.g., infliximab, golimumab, adalimumab, vedolizumab, ustekinumab, natalizumab, certolizumab) for the treatment of UC within 6 months prior to first screening visit. 14. Use of tofacitinib, oral cyclosporine, tacrolimus, mycophenolate mofetil, or methotrexate within 4 weeks prior to first screening visit. 15. Use of dihydroorotate dehydrogenase inhibitors leflunomide/teriflunomide within 6 months prior to first screening visit. 16. Use of OATP1B1/OATP1B3 substrates, OATP1B1/OATP1B3 inhibitors, and OAT3 inhibitors within 2 weeks or 5 × respective half-life (whichever is longer) prior to first screening visit. 17. Use of other investigational product within 8 weeks or 5 × the respective half-life (whichever is longer) prior to first screening visit and during the entire study. 18. Use of oral corticosteroids >20 mg/day, intravenous corticosteroids, or rectal and topical corticosteroids/aminosalicylates within 4 weeks prior to first screening visit. 19. Unable to attend study visits or comply with procedures. 20. Concurrent participation in any other interventional study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To assess the safety and tolerability of a once-daily multiple oral administration of KSP-0243 in patients with UC; - To characterise the pharmacokinetic (PK) of a once-daily multiple oral administration of KSP-0243 in patients with UC.;Secondary Objective: -To assess the pharmacodynamic (PD) response in faecal calprotectin (fCP) and C-reactive protein (CRP) following a once-daily multiple oral administration of KSP-0243 in patients with UC -To evaluate changes in clinical activity following a once-daily multiple oral administration of KSP-0243 in patients with UC. -Change from baseline in HIF-1a positive cell count on Day 28 -Change from baseline in gene expression profiling (RNA-seq) on Day 28 -Change from baseline in mucosal barrier-related proteins, ie, claudin-1 (CLDN1), mucin 3 (MUC3), ß-defensin 1 (DEFB1), and trefoil factor 3 (TFF3) levels, on Day 28 -Change from baseline in serum leucine-rich alpha 2 glycoprotein (LRG) level on Days 7, 14, 21, 28 (EOT), and 56 (EOS) -Change from baseline in prostaglandin E-major urinary metabolite (PGE-MUM) level on Days 7, 14, 21, 28 (EOT), and 56 (EOS);Primary end point(s): The primary safety endpoints are: • incidence and severity of adverse events (AEs)/treatment-emergent AEs (TEAEs) • incidence and severity of adverse drug reactions (ADRs) • clinical laboratory assessments (haematology, biochemistry, urinalysis, and hematopoietic and coagulation markers) • 12-lead ECG • vital signs • physical examinations. ;Timepoint(s) of evaluation of this end point: •For the primary endpoint: incidence and severity of adverse events (AEs)/treatment-emergent AEs (TEAEs), the timepoint is from the time ICF is signed until follow-up (EOS) visit. •For the primary endpoint: incidence and severity of adverse drug reactions (ADRs, the timepoint is from the first treatment administration until follow-up (EOS) visit. •For the primary endpoints: clinical laboratory assessments, 12-lead ECG, vital signs, physical examinat | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of patients achieving clinical response on Day 28 (defined as a reduction in Mayo Score of =3 points and =30% from baseline with either RBS of 0 or 1 or a reduction in RBS of =1 among patients with baseline RBS >0 and baseline mMES sigmoid >0) • Proportion of patients achieving clinical remission on Day 28 (defined as a Mayo Score of =2 with no individual subscore >1 among patients with baseline mMES sigmoid >0) • Proportion of patients achieving endoscopic improvement on Day 28 (defined as a mMES of 0 or 1 among patients with a baseline mMES >1) • Proportion of patients with improvement in RBS on Day 28 (defined as a decrease in RBS =1 among patients with baseline RBS >0) • Proportion of patients with resolution of RB on Day 28 (defined as RBS =0 among patients with baseline RBS >0). Proportion of patients achieving histologic response on Day 28 (defined as a decrease from baseline in RHI =7 among patients with a baseline RHI =7) • Proportion of patients achieving histologic remission on Day 28 (defined as RHI =3 with lamina propria neutrophils subscore =0 and neutrophils in epithelium subscore =0 among patients with both baseline subscores >0) • Proportion of patients achieving mucosal healing on Day 28 (defined as histologic remission + endoscopic improvement) • Proportion of patients achieving minimum histologic disease activity on Day 28 (defined as RHI 2). ;Timepoint(s) of evaluation of this end point: For the secondary end points, timepoint of evaluation is up to 28 days. | — |
Countries
Georgia, Moldova, Republic of, Romania
Contacts
Public ContactClinical Project Management
Kissei Pharmaceutical Co., Ltd.
Outcome results
None listed