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Safety and Tolerability of A3907 in Primary Sclerosing Cholangitis

Primary Purpose

Primary Sclerosing Cholangitis

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
A3907
Sponsored by
Albireo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Sclerosing Cholangitis focused on measuring PSC, Primary Sclerosing Cholangitis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key inclusion criteria: Clinical and radiological diagnosis of large-duct PSC via magnetic resonance cholangiopancreatography movement-related cortical potential (MRCP) or equivalent imaging modality that excludes biliary obstruction and malignancy within 6 months before screening Alkaline phosphatase (ALP) > 1.5 × upper limit of normal (ULN) but ≤ 10 × ULN Total bilirubin < 3 × ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN Baseline serum bile acid level at Screening must be > ULN Clinically stable for at least 3 months prior to screening Key exclusion criteria: 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 Biliary intervention within 3 months prior to study enrollment or planned Inflammatory bowel disease (IBD) with uncontrolled moderate to severe activity and/or on treatment with any immunosuppressive, immunomodulator, or biologic agent for treatment of IBD. Treatment with corticosteroids in the previous 4 weeks History of human immunodeficiency virus infection or any other known relevant infection (e.g., tuberculosis) History of colostomy or colectomy History of malignancy, including hepatocellular carcinoma 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 History of transplants, including liver transplantation, or currently on active transplantation list Known or suspected overlapping clinical and histologic diagnosis of autoimmune hepatitis Liver cirrhosis as assessed by any of the following: historical liver histology suspected liver fibrosis liver stiffness measurement, assessed by FibroScan (FibroScan value > 14.4 kPa) current or history of signs and symptoms of hepatic decompensation (including, but not limited to, jaundice, ascites, variceal haemorrhage, and/or hepatic encephalopathy) Treatment with rifampicin, CYP3A4 substrates, vitamin D or fibrates (unless patient is on a stable dose ≥ 6 months prior to baseline) and with medications that slow gastrointestinal motility Exposure to an investigational drug, biologic agent, or medical device within 30 days prior to Screening, or 5 half-lives of the study agent, whichever is longer Platelet count < 150 000/mm3 Albumin level < 3.0 g/dL International normalised ratio (INR) > 1.4 (the patient may be treated with vitamin K intravenously, and if INR is ≤ 1.4 at resampling, the patient may be enrolled) Advanced renal disease glomerular filtration rate (GFR) <70 mL/min/1.73 m2)

Sites / Locations

  • Hopital Saint AntoineRecruiting
  • ASST di Monza - Azienda Ospedaliera San GerardoRecruiting
  • Azienda Ospedale Università PadovaRecruiting
  • Hospital Clinic de BarcelonaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

10 mg (Arm 1)

30 mg (Arm 2)

Arm Description

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

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

Outcomes

Primary Outcome Measures

Treatment related adverse events
Number of participants with treatment related adverse events as assessed by CTCAE v 5.0

Secondary Outcome Measures

PK parameters for A3907 including, but not limited to, maximum observed plasma concentration (Cmax), and area under the plasma concentration time curve (AUC)
Change in serum and urine individual and total bile acid levels
Change in ALT, AST, gamma-glutamyltransferase (GGT), ALP and bilirubin levels
Change in serum C4 level

Full Information

First Posted
November 23, 2022
Last Updated
August 22, 2023
Sponsor
Albireo
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1. Study Identification

Unique Protocol Identification Number
NCT05642468
Brief Title
Safety and Tolerability of A3907 in Primary Sclerosing Cholangitis
Official Title
An Open Label, Phase 2 Study to Evaluate the Effect of A3907 on Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Adults With Primary Sclerosing Cholangitis (PSC)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 23, 2023 (Actual)
Primary Completion Date
June 17, 2024 (Anticipated)
Study Completion Date
June 17, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Albireo

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).
Detailed Description
The primary goal of this study in participants with PSC who are treated with A3907 is to assess the safety and tolerability of A3907 following repeat doses. Secondary goals include evaluation of the pharmacokinetic properties of A3907 (the study of how the body interacts with A3907 for the entire duration of exposure) and changes in safety parameters via laboratory testing such as liver enzymes, bile acid levels and markers of bile acid synthesis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis
Keywords
PSC, Primary Sclerosing Cholangitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
10 mg (Arm 1)
Arm Type
Experimental
Arm Description
10mg tablet A3907 administered orally once daily for 12 weeks.
Arm Title
30 mg (Arm 2)
Arm Type
Experimental
Arm Description
30mg (3x10 mg tablets) A3907 administered orally once daily for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
A3907
Intervention Description
A3907 is an oral, systemically available, potent inhibitor of the apical sodium bile acid transporter (ASBT).
Primary Outcome Measure Information:
Title
Treatment related adverse events
Description
Number of participants with treatment related adverse events as assessed by CTCAE v 5.0
Time Frame
From baseline through week 12
Secondary Outcome Measure Information:
Title
PK parameters for A3907 including, but not limited to, maximum observed plasma concentration (Cmax), and area under the plasma concentration time curve (AUC)
Time Frame
From baseline through week 12
Title
Change in serum and urine individual and total bile acid levels
Time Frame
From baseline through week 12
Title
Change in ALT, AST, gamma-glutamyltransferase (GGT), ALP and bilirubin levels
Time Frame
From baseline through week 12
Title
Change in serum C4 level
Time Frame
From baseline through week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key inclusion criteria: Clinical and radiological diagnosis of large-duct PSC via magnetic resonance cholangiopancreatography movement-related cortical potential (MRCP) or equivalent imaging modality that excludes biliary obstruction and malignancy within 6 months before screening Alkaline phosphatase (ALP) > 1.5 × upper limit of normal (ULN) but ≤ 10 × ULN Total bilirubin < 3 × ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN Baseline serum bile acid level at Screening must be > ULN Clinically stable for at least 3 months prior to screening Key exclusion criteria: 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 Biliary intervention within 3 months prior to study enrollment or planned Inflammatory bowel disease (IBD) with uncontrolled moderate to severe activity and/or on treatment with any immunosuppressive, immunomodulator, or biologic agent for treatment of IBD. Treatment with corticosteroids in the previous 4 weeks History of human immunodeficiency virus infection or any other known relevant infection (e.g., tuberculosis) History of colostomy or colectomy History of malignancy, including hepatocellular carcinoma 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 History of transplants, including liver transplantation, or currently on active transplantation list Known or suspected overlapping clinical and histologic diagnosis of autoimmune hepatitis Liver cirrhosis as assessed by any of the following: historical liver histology suspected liver fibrosis liver stiffness measurement, assessed by FibroScan (FibroScan value > 14.4 kPa) current or history of signs and symptoms of hepatic decompensation (including, but not limited to, jaundice, ascites, variceal haemorrhage, and/or hepatic encephalopathy) Treatment with rifampicin, CYP3A4 substrates, vitamin D or fibrates (unless patient is on a stable dose ≥ 6 months prior to baseline) and with medications that slow gastrointestinal motility Exposure to an investigational drug, biologic agent, or medical device within 30 days prior to Screening, or 5 half-lives of the study agent, whichever is longer Platelet count < 150 000/mm3 Albumin level < 3.0 g/dL International normalised ratio (INR) > 1.4 (the patient may be treated with vitamin K intravenously, and if INR is ≤ 1.4 at resampling, the patient may be enrolled) Advanced renal disease glomerular filtration rate (GFR) <70 mL/min/1.73 m2)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Albireo
Phone
+1(857) 378-2035
Email
medinfo@albireopharma.com
Facility Information:
Facility Name
Hopital Saint Antoine
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karima Ben Belkacem
Phone
+33149282380
Email
karima.benbelkacem@aphp.fr
First Name & Middle Initial & Last Name & Degree
Olivier Chazouilleres, MD
Facility Name
ASST di Monza - Azienda Ospedaliera San Gerardo
City
Monza
ZIP/Postal Code
20900
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabriella Marsoni
Phone
+390392333962
Email
g.marsoni.sc@gmail.com
First Name & Middle Initial & Last Name & Degree
Riccardo Artuso
Phone
+390392334598
Email
r.artusosc@gmail.com
First Name & Middle Initial & Last Name & Degree
Marco Carbone, MD
Facility Name
Azienda Ospedale Università Padova
City
Padova
ZIP/Postal Code
35128
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emanuela Bonaiuto
Phone
+390498215611
Email
emanuela.bonaiuto@gmail.com
First Name & Middle Initial & Last Name & Degree
Nora Cazzagon, MD
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
ZIP/Postal Code
8036
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cristina Marti
Phone
+34697267846
Email
cmartid@clinic.cat
First Name & Middle Initial & Last Name & Degree
María Carlota Londoño Hurtado, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Safety and Tolerability of A3907 in Primary Sclerosing Cholangitis

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