Study to Evaluate the Safety, Tolerability, PDs, and Efficacy of CNP-104 in Subjects With Primary Biliary Cholangitis

NCT05104853 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CNP-104-5.001
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 19

Brief Summary

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.

Conditions

Primary Biliary Cholangitis

Outcome Measures

Primary Outcomes (3)

• 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

  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.

  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

  through CNP-Dosing Period, an average of 15 Days

Secondary Outcomes (7)

• To assess the change from baseline in Serum Alkaline Phosphatase (ALP) levels, for safety only

  through Visit 6, an average of 60 Days and Visit 16, an average of 720 Days

• To assess the change from baseline in AMA

  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

  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

  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

  through Visit 6, an average of 60 Days and Visit 16, an average of 720 D

Study Arms (3)

4 mg/Kg CNP-104

EXPERIMENTAL

200 mL intravenous infusion on Day 1 and Day 8: 4 mg/Kg CNP-104

Drug: CNP-104

8 mg/Kg CNP-104

EXPERIMENTAL

200 mL intravenous infusion on Day 1 and Day 8: 8 mg/Kg CNP-104

Drug: CNP-104

Placebo

PLACEBO COMPARATOR

200 mL intravenous infusion on Day 1 and Day 8: Placebo

Drug: Placebo

Interventions

CNP-104 DRUG

CNP-104 is comprised of PDC-E2 peptide dispersed within a negatively charged polymer matrix of poly (lactic-co-glycolic acid) (PLGA) particles at a target concentration of \~1 μg of PDC-E2 peptide per mg of PLGA particles.

4 mg/Kg CNP-104; 8 mg/Kg CNP-104

Placebo DRUG

CNP-104 Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who are willing and able to provide Institutional Review Board (IRB) approved written informed consent and privacy language as per national regulations.
• Men and non-pregnant women, ages 18-75 years inclusive.
• Subjects with a PBC diagnosis as demonstrated by the presence of 2 or more of the following 3 diagnostic factors:
• Alkaline phosphatase \> 1.5× ULN for at least 6 months
• Positive AMA titer or, if AMA negative or in low titer (\<1:40), positive PBC-specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components \[PDC-E2, 2-oxo-glutaric acid dehydrogenase complex\])
• Liver biopsy findings consistent with PBC
• Subjects who are unresponsive to UDCA and/or OCA after 6 months of treatment at a stable dose as measured by ALP \> 1.5× ULN.
• For subjects on any medication used to treat the symptoms of PBC (ex. UDCA, OCA, seladelpar), subjects must be on a stable dose for a minimum of 3 months prior to enrollment and must agree not to change their dose through study Day 60 unless reviewed by the medical monitor and approved by the site investigator.
• Subjects with ALP \> 1.5× ULN.
• Subjects with AST and ALT \< 5× ULN.
• Subjects with hemoglobin ≥ 10 g/dL.
• Subjects with total bilirubin \< 2× ULN.
• Men and women of child-bearing potential (WOCBP) must agree to practice a highly effective method of contraception that may include, but is not limited to, abstinence, sex only with persons of the same sex, monogamous relationship with vasectomized partner, vasectomy, hysterectomy, bilateral tubal ligation, licensed hormonal methods, intrauterine device (IUD) beginning at the time of screening through Day 90.
• Female subjects who agree not to donate ova starting at initial screening and through Day 90.
• Male subjects who agree to not donate sperm starting at screening and through Day 90.

You may not qualify if:

• Subjects with a Class B or Class C Child-Pugh score.
• Subjects with concomitant liver diseases including chronic viral hepatitis B or C, autoimmune hepatitis, PSC, alcoholic liver disease, Wilson's disease, hemochromatosis, or Gilbert's syndrome.
• Subjects who have previously undergone liver transplantation.
• Subjects with decompensated liver disease as defined by the presence or history of any of the following:
• MELD score \> 15
• Hepatic encephalopathy
• Ascites
• Hepatorenal syndrome or serum creatinine \> 2 mg/dL
• Total Bilirubin \> 3.0 mg/dL
• INR \>1.8 unless on anticoagulation such as Coumadin
• History of variceal hemorrhage
• Subjects with a history of cerebrovascular accident in the past 12 months.
• Subjects with history of myocardial infarction, as defined by any of the following criteria:
• Development of pathological Q waves with or without symptoms
• Imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause

Sponsors & Collaborators

• COUR Pharmaceutical Development Company, Inc.: lead

Study Sites (19)

Southern California Research Center

Coronado, California, 92118, United States

Location

OM Research

Lancaster, California, 93534, United States

Location

University of California Davis Health

Sacramento, California, 95817, United States

Location

Peak Gastroenterology Associates

Colorado Springs, Colorado, 80907, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06520, United States

Location

University of Florida - Hepatology Research

Gainesville, Florida, 32610, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Florida Research Institute

Lakewood Rch, Florida, 34211-4930, United States

Location

GI PROS Research

Naples, Florida, 34102, United States

Location

Cleveland Clinic - Florida

Weston, Florida, 33331, United States

Location

Digestive Healthcare of Georgia

Atlanta, Georgia, 30309, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Henry Ford Health System

Novi, Michigan, 48377, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Related Publications (1)

• Klatzkow H, Bhavsar-Burke I, Pearson M, Wentworth BJ. Primary Biliary Cholangitis in 2025: A New Frontier. Am J Gastroenterol. 2025 Dec 1;120(12):2746-2749. doi: 10.14309/ajg.0000000000003559. Epub 2025 May 29. No abstract available.

  PMID: 40439725 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Christopher Bowlus, MD

  UC Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2021
• First Posted: November 3, 2021
• Study Start: January 25, 2022
• Primary Completion: January 30, 2026
• Study Completion: January 30, 2026
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)