Safety and Tolerability of A3907 in Primary Sclerosing Cholangitis

NCT05642468 | Terminated Phase 2 Results

• 2 other identifiers: A3907-0022022-500790-14-00
• Study Type: interventional
• Target: 18
• Locations: 4 countries
• Sites: 8

Brief Summary

This study will test a drug called A3907 to see how safe and tolerated it is for treating people with Primary Sclerosing Cholangitis (PSC).

Conditions

Primary Sclerosing Cholangitis

Keywords

PSC; Primary Sclerosing Cholangitis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  An adverse event (AE) was any untoward medical occurrence in an enrolled participant regardless of causal relationship with study drug. An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or an important medical event. A TEAE was any AE or worsening of an existing disease that occurred after the first dose of study drug and within the 14-day follow-up.

  From first dose of study drug (Day 1) up to 14 days post last dose, approximately 112 days

Secondary Outcomes (7)

• Maximum Observed Plasma Concentration (Cmax) of A3907

  Pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10 hours post-dose on Days 0 and 98

• Area Under the Plasma Concentration-time Curve From Time Zero to Time t (Time of Last Quantifiable Plasma Concentration) (AUC0-t) of A3907

  Pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10 hours post-dose on Days 0 and 98

• Change From Baseline to Week 12 in Serum and Urine Individual and Total Bile Acid Levels

  Baseline (Day 1) and Week 12

• Change From Baseline to Week 12 in Liver Biochemical Tests (LBTs): Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT) and Alkaline Phosphatase (ALP)

  Baseline (Day 1) and Week 12

• Change From Baseline to Week 12 in Liver Biochemical Tests: Total and Direct Bilirubin Levels

  Baseline (Day 1) and Week 12

Study Arms (4)

10 mg (Arm 1)

EXPERIMENTAL

10mg tablet A3907 administered orally once daily for 12 weeks.

Drug: Ritivixibat

30 mg (Arm 2)

EXPERIMENTAL

30mg (3x10 mg tablets) A3907 administered orally once daily for 12 weeks.

Drug: Ritivixibat

30 mg BID (Arm 3)

EXPERIMENTAL

30mg (3x10 mg tablets) A3907 administered orally Bi-daily for 12 weeks.

Drug: Ritivixibat

30 mg BID for CRS (Arm 4)

EXPERIMENTAL

30mg (3x10 mg tablets) A3907 administered orally Bi-daily for 12 weeks.

Drug: Ritivixibat

Interventions

Ritivixibat DRUG

10mg tablet A3907 administered orally

10 mg (Arm 1); 30 mg (Arm 2); 30 mg BID (Arm 3); 30 mg BID for CRS (Arm 4)

Eligibility Criteria

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

You may qualify if:

• Adults between 18 and 75 years of age (inclusive)
• Clinical diagnosis of large-duct PSC as evidenced by chronic cholestasis with evidence of more than 6 months duration with either a consistent magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) showing sclerosing cholangitis. and historical evidence of elevated alkaline phosphatase (ALP).
• Willing to sign informed consent.
• Women of childbearing potential (WOCBP) and males with female partners of childbearing potential must agree to use contraception. Women of nonchildbearing potential (WONCBP) have a confirmatory follicle-stimulating hormone \[FSH\] level ≥ 40 mIU/mL
• Alkaline phosphatase Phosphatase (ALP) value \> 1.5 × upper limit of normal (ULN) but ≤ 10 × ULNULN at Visit 1 (Screening Period). Before starting 12 weeks treatment variability of \< 30% between ALP values at Visit 1 and Visit 2 must be confirmed. If variability is \> 30 % a third ALP value may be obtained. If the third ALP value meets \>1.5 × ULN but ≤ 10 × ULN the patient can start the 12-week treatment period.
• Arms 1-3 Only: Total bilirubin \< 1.5 × ULN (unless due to Gilberts Syndrome or hemolysis) and normal direct bilirubin.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN
• Serum bile acid level \> ULN
• Arms 1 - 3 Only: An MRCP or equivalent imaging modality performed within 6 months before the Screening Period that is consistent with PSC without a clinically relevant stricture.
• Use of ursodeoxycholic acid (UDCA) with a total daily dose ≤ 23 mg/kg/day, or bile acid-binding resins are permitted, with a minimum of 3 months of stable treatment prior to the Screening Period, and expected to remain on a stable dose through the 12-week treatment period; or a minimum of 3 months off UDCA prior to the Screening Period if UDCA was recently discontinued.
• If a patient has inflammatory bowel disease (IBD) with a minimum disease duration of 4 weeks, this diagnosis should be documented. Inflammatory bowel disease should be in clinical remission or mildly active according to Crohn's Disease Activity Index (CDAI), partial Mayo score for Crohn's Disease (CD) and ulcerative colitis (UC), respectively (i.e. patients with CDAI score \< 220 and Mayo score \< 5, respectively). Patients with IBD should have had a colonoscopy performed within one year prior to the Screening Period with results showing no evidence of dysplasia or cancer
• Clinically stable for at least 3 months prior to the Screening Period.
• Arm 4 Only: One stable clinically relevant biliary stricture of at least 4 weeks duration on contrast-enhanced MRI/MRCP with \> 75% reduction of duct diameter in the common bile duct or hepatic duct without suspicion of cholangiocarcinoma (further established by imaging and stable CA 19-9 below ULN repeated twice over 1 month), or cholelithiasis. Subjects may have signs or symptoms of worsening obstructive cholestasis (increasing jaundice, nausea, anorexia, steatorrhea and worsening or new onset pruritus), deterioration of liver function (i.e. decreasing platelet count, increasing international normalized ratio \[INR\]) and/could be listed for liver transplantation due to their clinically relevant biliary stricture.
• Arm 4 Only: MELD Score \< 35

You may not qualify if:

• Presence of documented secondary sclerosing cholangitis, small duct PSC, known or suspected overlapping clinical and histologic diagnosis of autoimmune hepatitis or other causes of chronic liver disease
• Arm 1-3 Only: Biliary intervention within 3 months prior to study enrollment or planned.
• Arm 4 Only: Planned Biliary intervention between the Screening Period and baseline.
• Presence of alternative causes of chronic liver disease, including alcohol-associated liver disease, nonalcoholic steatohepatitis, primary biliary cholangitis, autoimmune hepatitis, or active hepatitis B or C.
• IBD with uncontrolled moderate to severe activity and/or on treatment with any immunosuppressive, immunomodulator, or biologic agent for treatment of IBD (i.e. azathioprine, 6 mercaptopurine, tacrolimus, methotrexate, infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, tofacitinib, ozanimod). Treatment with corticosteroids (including budesonide, budesonide MMX and beclomethasone) in the previous 4 weeks.
• History of human immunodeficiency virus infection or any other known relevant infection (e.g. tuberculosis).
• History of ileectomy, colostomy or colectomy.
• History of malignancy, including hepatocellular carcinoma and cholangiocarcinoma within the past 10 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
• Alpha-fetoprotein (AFP) \> 20 ng/mL (at the Screening Visit) with 4-phase liver CT or MRI suggesting presence of liver cancer.
• History of transplants, including liver transplantation, or currently on active transplantation list (Arms 1 3). Arm 4 may be on an active liver transplantation list.
• Current or a history of hepatic decompensation events including, but not limited to ascites, encephalopathy, or history of esophageal variceal bleeding.
• Known or suspected overlapping clinical and histologic diagnosis of autoimmune hepatitis.
• Small duct PSC (evidence of PSC on historical liver histology, with normal bile ducts on cholangiography) without large duct PSC.
• Liver cirrhosis as assessed by any of the following:
• historical liver histology.

Sponsors & Collaborators

• Albireo, an Ipsen Company: lead

Study Sites (8)

Hopital Saint Antoine

Paris, 75012, France

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy

Location

ASST di Monza - Azienda Ospedaliera San Gerardo

Monza, 20900, Italy

Location

Azienda Ospedale Università Padova

Padova, 35128, Italy

Location

Centrum Medyczne INTER-MED

Częstochowa, Poland

Location

Uniwersyteckie Centrum Kliniczne im. Prof. Kornela Gibinskiego

Katowice, Poland

Location

ID Clinic Arkadiusz Pisula

Mysłowice, Poland

Location

Hospital Clinic de Barcelona

Barcelona, 8036, Spain

Location

Related Links

• Lay language results summary

MeSH Terms

Conditions

Cholangitis, Sclerosing

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Limitations and Caveats

The study was terminated early due to Sponsor decision, not due to any safety concerns. No participant was enrolled in A3907 30 mg BID without CRS arm as the study was terminated prior to enrollment in that arm.

Results Point of Contact

• Title: Medical Director
• Organization: Ipsen

clinical.trials@ipsen.com

see email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2022
• First Posted: December 8, 2022
• Study Start: January 9, 2023
• Primary Completion: July 10, 2025
• Study Completion: July 10, 2025
• Last Updated: May 4, 2026
• Results First Posted: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• Access Criteria: Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Locations

IT (3); FR (1); PL (3); ES (1)