Primary Sclerosing Cholangitis MedDRA version: 20.1 Level: LLT Classification code 10036732 Term: Primary sclerosing cholangitis System Organ Class: 100000004871
Conditions
Sponsors
ChemomAb Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females, age 18 to 75 years, both inclusive. 2. Subjects with diagnosis of large duct PSC (intrahepatic and/or extrahepatic), of more than 24 weeks’ duration (defined as cholestatic serum liver tests with consistent magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) showing sclerosing cholangitis once secondary causes of sclerosing cholangitis have been excluded). 3. Subjects that have had no significant clinical concern for cholangiocarcinoma based on clinical, laboratory or imaging findings in the 12 months preceding Randomization. 4. Subjects with serum ALP greater than 1.5 × upper limit of normal (ULN) in both Screening and Baseline blood tests (taken at least 5 days apart). 5. Subjects receiving Ursodeoxycholic Acid (UDCA), must recieve a stable dose for =12 weeks prior to, Randomization and must not exceed 23 mg/kg/day during this time. 6. Subjects with concomitant IBD: a. Subjects with ulcerative colitis (UC) must have undergone colonoscopy with biopsy confirming no dysplasia or colorectal cancer within 18 months of Randomization; b. Subjects with Crohn’s Disease (CD) must be in remission as defined by a Crohn’s Disease Activity Index (CDAI) 12 weeks prior to Randomization. 8. Female subjects of childbearing potential (defined as sexually mature women who have not undergone surgical sterilization or who have not been naturally post-menopausal for at least 24 consecutive months for women =55 years; for women >55 years 12 consecutive months) must have a negative serum pregnancy test prior to starting study treatment. Sexually active women of childbearing potential must agree to use a highly effective method of contraception from the Screening Visit throughout the study period including 18 weeks post last dose. Highly effective methods of contraception are considered to be those listed below: • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: o oral o intravaginal o transdermal • Progestogen-only hormonal contraception associated with inhibition of ovulation: o oral o injectable o implantable • Intrauterine device • Intrauterine hormone-releasing system • Bilateral tubal occlusion • Vasectomy (partner) • Abstinence, if in line with the preferred and usual lifestyle of the subject [where abstinence is defined as refraining from heterosexual intercourse during the trial duration (from first administration of investigational product until 18 weeks post last dose)]. 9. Male subjects, if not vasectomized, must agree to use barrier contraception (condom plus spermicide) during heterosexual intercourse from screening through to study completion and for 90 days from the last dose of study investigational medicinal product. 10. Subjects able to understand and sign a written informed consent form (ICF). 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 34 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects with presence of documented secondary sclerosing cholangitis (such as ischemic cholangitis, recurrent pancreatitis, intraductal stone disease, severe bacterial cholangitis, surgical or blunt abdominal trauma, recurrent pyogenic cholangitis, choledocholithiasis, toxic sclerosing cholangitis due to chemical agents, or any other cause of secondary sclerosing cholangitis) on prior clinical investigations. 2. Subjects with presence of competing etiology of liver disease (including, but not limited to, viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis, (Ig) G4-associated cholangitis, primary biliary cholangitis etc.) are excluded from the study. Subjects with possible overlap syndrome with autoimmune hepatitis are excluded if the Investigator considers autoimmune hepatitis as the predominant liver injury. 3. Subjects with small duct PSC in the absence of large duct disease. 4. Subjects with percutaneous biliary drain or bile duct stent or subjects who had required biliary drainage within 12 weeks of screening. 5. Subjects that have undergone prior biliary surgery (laparoscopic or open surgery) other than those who at the time of screening are more than 6 weeks after cholecystectomy without surgical complications. 6. Subjects with evidence of cirrhosis, as determined by local transient elastography (TE, preferably FibroscanTM) values of >/= 14.4 kPa obtained during the screening period. 7. History of cirrhosis and/or hepatic impairment (Child-Pugh classes A, B and C), and/or hepatic decompensation including ascites, encephalopathy or variceal bleeding. 8. Subjects who have undergone or are planned for liver transplantation or with current model of end stage liver disease (MELD) score =12. 9. Subjects with Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values > 5 x ULN as determined at Screening and/or Randomization blood tests (taken at least 5 days apart). 10. Subjects who show ‘clinically significant changes’ (as judged by the investigator) in liver transaminase levels on repeated measure will be excluded. 11. Subjects with serum Total Bilirubin values > 2 x ULN at Screening and/or at Randomization (taken at least 5 days apart). Subjects who show evidence of ‘clinically significant worsening’ (as judged by the investigator) of bilirubin between screening and Randomization will be excluded. 12. Subjects with known Gilbert's syndrome or a history of elevations in unconjugated (indirect) bilirubin >ULN. 13. Subjects with International Normalized Ratio (INR) >1.3 which does not correct on vitamin k replacement, in the absence of anticoagulants. 14. Subjects with serum creatinine >1.4 mg/dL (123 µmol/L) and/or a platelet count 129 U/mL) within 12 months prior to at Screening, unless Ca 19-9 levels have been stable and clinical evaluation & repeated MRI imaging within the same time period has not provided evidence of cholangiocarcinoma. 17. Subjects with a prior biliary stricture necessitating intervention should be stable for =24 weeks prior to Randomization without intervention, or episode of cholangitis, and should show a low level of clinical suspicion of cholangiocarcinoma. 18. Subjects with current known portal hyper
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety, tolerability and activity of the anti-human CCL24 monoclonal antibody CM-101, over 15 weeks, in male and female adult subjects with primary sclerosing cholangitis, as measured by a decrease in alkaline phosphatase (ALP) levels and reduction in ELF score (two primary end-points).;Secondary Objective: To evaluate the CM-101 pharmacokinetic (PK) and pharmacodynamic (PD) profiles, anti-drug antibodies (ADA) development, biochemical response to treatment (liver enzyme levels) and a panel of biomarkers to monitor disease progression in PSC.;Primary end point(s): 1. Change from baseline through to Week 15 in serum alkaline phosphatase levels by treatment cohort 2. Change from baseline through to Week 15 in Enhanced Liver Fibrosis (ELF) score by treatment cohort;Timepoint(s) of evaluation of this end point: 1) and 2) from baseline through to Week 15 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Analyses of ALP response rates, defined as reduction of ALP to 1.3 x ULN, or a combination of ALP reduction to 1.5-1.3 x ULN with an at least 40% reduction from baseline 2. Percent change from baseline over time in liver enzymes (ALT, AST and GGT) 3. Change from baseline through to Week 15 in liver fibrosis markers - such as PRO-C3 and PRO-C5 4. Evaluation of the incidence and characteristics of treatment emergent adverse events (TEAEs) occurring following repeated administrations of CM-101 5. Elucidation of the Serum PK profile of repeated administrations of CM-101 6. Evaluation of the development of anti-drug antibodies (ADA) following repeated administrations of CM-101;Timepoint(s) of evaluation of this end point: 1) Refer to schedule of events 2) Change from baseline over time 3) Baseline through to Week 15 4) Duration of study 5) Refer to schedule of events 6) Refer to schedule of events | — |
Countries
Israel, Spain, United Kingdom
Contacts
Public Contact-
ChemomAb Ltd.
Outcome results
None listed