Treatment of Primary Sclerosing Cholangitis MedDRA version: 20.1 Level: LLT Classification code 10036732 Term: Primary sclerosing cholangitis System Organ Class: 100000004871
Conditions
Interventions
Product Name: CM-101
Pharmaceutical Form: Solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the
Sponsors
ChemomAb Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all inclusion criteria to be eligible for the study: 1. Males and females, Age 18 Years to 75 Years, both inclusive 2. Subjects with diagnosis of large duct PSC (intrahepatic and/or extrahepatic), of more than 6 months duration, based on the EASL 2009 cholestatic guidelines definition (cholestatic liver function tests with consistent magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) showing sclerosing cholangitis, +/- a liver biopsy consistent with PSC once secondary causes of sclerosing cholangitis have been excluded). Note: Subjects must have cholangiographic changes showing sclerosing cholangitis in order to be eligible for the study. 3. Subjects must have a recent (within 12 months of Day 0) imaging surveillance that is interpreted by the investigator as low risk for cholangiocarcinoma. The minimum imaging requirement is a transabdominal ultrasound however other imaging modalities such as CT or MR are also accepted. Note: Subjects that do not have such imaging will have a transabdominal ultrasound done as part of the screening procedures. 4. Subjects with serum ALP greater than 1.5 × upper limit of normal (ULN) as determined by the mean of the Screening and Baseline values 5. Subjects receiving Ursodeoxycholic acid (UDCA), must have been stable for =3 months prior to, and including, Day 0 and must not have exceeded 20 mg/kg/day during this time. 6. For subjects with concomitant IBD: a. Colonoscopy or other appropriate endoscopic procedure within 12-18 months of Day 0 confirming no dysplasia or colorectal cancer b. Subjects with Crohn’s Disease (CD) must be in remission as defined by a Crohn’s Disease Activity Index (CDAI) 3 months prior to study Day 0 8. Female subjects of childbearing potential must have a negative serum/urine pregnancy test prior to starting study treatment. Sexually active women of childbearing potential must agree to use an effective method of contraception from the Screening Visit throughout the study period including the 15 weeks post last dose follow-up period. Effective methods of contraception are considered to be those listed below: • Barrier method, i.e., (a) condom (male or female) with spermicide or (b) diaphragm with spermicide; or • Intrauterine device; or • Vasectomy (partner), or • Hormonal (e.g., contraceptive pill, patch, intramuscular implant or injection) • 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 the end of the 15 weeks post last dose follow-up period)] 9. Male subjects, if not vasectomized, must agree to use barrier contraception (con
Exclusion criteria
Exclusion criteria: Subjects must not meet any exclusion criteria to be eligible for the study: 1. Subjects with presence of documented 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, primary biliary cirrhosis etc. 3. Subjects with evidence of autoimmune immunoglobin (Ig) IgG4-associated cholangitis, 4. Subjects with small duct cholangitis in the absence of large duct disease. 5. Subjects with percutaneous biliary drain or bile duct stent 6. 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 7. Subjects with evidence of cirrhosis, as determined by local transient elastography taken within 6 months of study screening. 8. History of cirrhosis and/or hepatic impairment (Child-Pugh classes A, B and C) and/or hepatic decompensation including ascites, encephalopathy or variceal bleeding 9. Subjects who have undergone or are planned for liver transplantation or current model of end stage liver disease 10. Subjects with Aspartate aminotransferase (AST) and alanine aminotransferase (ALT); above the allowed cut-offs, 11. Subjects with Total Bilirubin > 2 x ULN 12. Subjects with International Normalized Ratio (INR) > 1.3 in the absence of anticoagulants 13. Subjects with serum creatinine >1.4 mg/dL (123 µmol/L) and/or platelet count 129 U/mL) at screening. 15. Subjects with a prior dominant biliary stricture necessitating biliary intervention should have been stable (Bilirubin 10% of their body weight during the 6 months prior to screening 18. Subjects that consume alcohol greater than 21 units/week for males or 14 units/week for females 19. Subjects experiencing cholangitis within last 90 days or ongoing need for prophylactic antibiotics 20. Subjects experiencing flare in colitis activity within 90 days of screening requiring intensification of therapy beyond baseline maintenance treatment 21. Subjects treated with the following medications =6 months of study Day 0 and throughout the trial: fenofibrate or other fibrates and potentially hepatotoxic medications
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine the activity of the anti-human CCL24 monoclonal antibody CM-101, administered over 12 weeks, in male and female adult subjects with primary sclerosing cholangitis, as measured by a decrease in alkaline phosphatase (ALP) levels.;Secondary Objective: To evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodinamic (PD) profiles, ADA development, biochemical response (liver enzyme levels) and a panel of biomarkers to monitor disease progression in PSC.; Primary end point(s): The Study primary objective is to determine the activity of the anti-human CCL24 monoclonal antibody CM-101, administered over 12 weeks, in male and female adult subjects with primary sclerosing cholangitis, as measured by a decrease in alkaline phosphatase (ALP) levels. 1. Percent change from baseline through Week 15 in serum alkaline phosphatase ;Timepoint(s) of evaluation of this end point: Week 15 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodinamic (PD) profiles, ADA development, biochemical response (liver enzyme levels) and a panel of biomarkers to monitor disease progression in PSC. Incidence and characteristics of adverse events (AEs) occurring following repeated administrations of CM-101 2. Elucidate the Serum PK profile of repeated administrations of CM-101. The following parameters and others will be calculated: - Maximum CM-101 plasma concentration (Cmax) - Time to Cmax (tmax) - Area under the curve (AUC) to the final concentration ? limit of quantitation (LOQ), AUC(0-t) and to infinity AUCinf - Terminal elimination rate constant (?z) - Terminal elimination half-life (T½) Additional parameters may be also calculated as deemed necessary 2. Evaluation of the development of anti-drug antibodies (ADA) following repeated administrations of CM-101 3. Percent change from baseline over time in liver enzymes (ALT, AST and GGT) 4. Change from baseline through Week 15 in markers of liver fibrosis- such as ELF™ Blood Test, PRO-C3 and PRO-C5 ;Timepoint(s) of evaluation of this end point: Week 27 | — |
Countries
Israel, United Kingdom
Contacts
Public ContactAdi Mor
ChemomAb Ltd.
Outcome results
None listed