This study is a Phase 2a First-in-Human (FIH) clinical trial to assess the safety, tolerability, pharmacodynamics (PD), and efficacy of multiple ascending doses of CNP-104. The study consists of a 120 day primary study followed by a 20 month long-term safety and durability of response follow-up period.
Subjects ages 18-75 with primary biliary cholangitis will be screened up to 14 days prior to enrollment into the study. Screening will be completed to assess eligibility, obtain vital signs, collect laboratory samples and PD measurements, and to receive a FibroScan for liver fibrosis. Subjects will additionally complete an initial PBC-40 assessment and begin an Itch Diary, a questionnaire and scoring system to be completed by the patient every morning and evening through Day 120 and then monthly through end of study. Subjects who meet all inclusion and no exclusion criteria after completing the screening visit will be enrolled in the study. Subjects will be randomized on Day 1 in a 1:1 ratio to receive either CNP-104 or Placebo (0.9% Sodium Chloride USP) by intravenous (IV) infusion. Subjects will be administered CNP-104 or Placebo on Day 1 and on Day 8. This study was originally designed with 2 cohorts, Cohort 1 comprised of 6 subjects randomized 1:1 to placebo or 4 mg/kg, and Cohort 2 comprised of up to 34 subjects randomized 1:1 to placebo or 8 mg/kg. Under Protocol Amendment 6 (v7.0), the remaining subjects for Cohort 2 (approximately 16) will be randomized 1:3:1 to placebo, 4 mg/kg, and 8 mg/kg respectively. Subjects will remain in the clinic on Day 1 and Day 8 from the time of admission (prior to administration of CNP-104 or Placebo) through the final procedure conducted 4 hours post-dose that same day unless an infusion reaction, or other adverse event, requires an extended duration of monitoring. Subjects will be discharged if safety parameters are acceptable to the investigator. Seven days after the second administration of CNP-104 or Placebo, subjects must return to the clinic for collection of safety labs, PD measurements, and assessment of AEs and medication changes. Subjects will continue to be followed for 2 years to assess safety, pharmacodynamics, and immunogenicity during the Post-Dosing period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
42
Southern California Research Center
Coronado, California, United States
OM Research
Lancaster, California, United States
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Frequency tables will be presented by treatment group for all AEs and SAEs by System Organ Class (SOC) and Preferred Term (PT). Frequency tables will also be produced by treatment group for AEs leading to discontinuation from TP and study, by severity, and by causality. No formal statistical testing will be done
Time frame: through Study Completion, an average of 720 Days
Laboratory safety assessments (hematology, serum chemistry, coagulation panel, urinalysis).
Frequency tables of each assessment abnormalities by grade and treatment will be presented. No formal statistical testing will be done.
Time frame: through Study Completion, an average of 720 Days
Serum Cytokines (TNF-α, IL-4, IL-6, IL-10, IL-1β, MCP-1, MIP-1α, IFN-γ)
Frequency tables will be presented by treatment group. No formal statistical testing will be done
Time frame: through CNP-Dosing Period, an average of 15 Days
To assess the change from baseline in Serum Alkaline Phosphatase (ALP) levels, for safety only
Change from baseline in ALP levels at Day 60 and Day 720
Time frame: through Visit 6, an average of 60 Days and Visit 16, an average of 720 Days
To assess the change from baseline in AMA
Change from baseline in AMA between placebo and CNP-104 at Day 90 and Day 720
Time frame: through Visit 7, an average of 90 Days and Visit 16, an average of 720 Days
To assess the change from baseline in liver fibrosis by FibroScan
Change from baseline in liver fibrosis by FibroScan between placebo and CNP-104 at Day 90 and Day 720
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University of California Davis Health
Sacramento, California, United States
Peak Gastroenterology Associates
Colorado Springs, Colorado, United States
Yale School of Medicine
New Haven, Connecticut, United States
University of Florida - Hepatology Research
Gainesville, Florida, United States
Mayo Clinic Florida
Jacksonville, Florida, United States
Florida Research Institute
Lakewood Rch, Florida, United States
GI PROS Research
Naples, Florida, United States
Cleveland Clinic - Florida
Weston, Florida, United States
...and 9 more locations
Time frame: through Visit 7, an average of 90 Days and Visit 16, an average of 720 Days
To assess the change from baseline in modified PBC-40 score
Change from baseline in modified PBC-40 score between placebo and CNP-104 at Day 60 and Day 720
Time frame: through Visit 6, an average of 60 Days and Visit 16, an average of 720 Days
To assess the change from baseline in Weekly Mean Itch Score
Change from baseline in Weekly Mean Itch Score between placebo and CNP-104 at Day 60 and Day 720
Time frame: through Visit 6, an average of 60 Days and Visit 16, an average of 720 D
To assess the change from baseline in liver enzymes (Albumin, Bilirubin (total and direct), ALT, AST, GGT)
Change from baseline in liver enzymes at Days 60 and 720
Time frame: through Visit 6, an average of 60 Days and Visit 16, an average of 720 Days
To assess the change in antigen specific CD4+ and CD8+ T cells
Change from baseline in antigen specific CD4+ and CD8+ T at Days 60 and 720
Time frame: through Visit 6, an average of 60 Days and Visit 16, an average of 720 Days