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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05014672




Registration number
NCT05014672
Ethics application status
Date submitted
10/08/2021
Date registered
20/08/2021
Date last updated
23/05/2024

Titles & IDs
Public title
A Trial of Setanaxib in Patients With Primary Biliary Cholangitis (PBC) and Liver Stiffness
Scientific title
TRANSFORM: A 24-week, Randomized, Placebo-controlled, Double-blind, Phase 2b Trial of Setanaxib in Patients With Primary Biliary Cholangitis (PBC) and Elevated Liver Stiffness
Secondary ID [1] 0 0
2021-001810-13
Secondary ID [2] 0 0
GSN000350
Universal Trial Number (UTN)
Trial acronym
TRANSFORM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Biliary Cholangitis 0 0
Liver Stiffness 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Setanaxib
Treatment: Drugs - Placebo

Experimental: Setanaxib 1200 mg/day - Participants will be administered setanaxib at a dose of 1200 mg/day for the 24-week double-blind treatment period.

Experimental: Setanaxib 1600 mg/day - Participants will be administered setanaxib at a dose of 1600 mg/day for the 24-week double-blind treatment period.

Placebo Comparator: Placebo - Participants will be administered a placebo for the 24-week double-blind treatment period.


Treatment: Drugs: Setanaxib
Oral tablets, 400mg per tablet

Treatment: Drugs: Placebo
Oral tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in ALP
Timepoint [1] 0 0
Baseline (Day 1) and Week 24
Secondary outcome [1] 0 0
Change from Baseline in Fatigue
Timepoint [1] 0 0
Baseline (Day 1) and Week 24
Secondary outcome [2] 0 0
Change from Baseline in Patient's Global Impression of Severity (PGIS) Fatigue
Timepoint [2] 0 0
Baseline (Day 1) and Week 24
Secondary outcome [3] 0 0
Change from Baseline in Patient's Global Impression of Change (PGIC) Fatigue
Timepoint [3] 0 0
Baseline (Day 1) and Week 24
Secondary outcome [4] 0 0
Change from Baseline in PBC-40 Fatigue Domain
Timepoint [4] 0 0
Baseline (Day 1) and Week 24
Secondary outcome [5] 0 0
Change from Screening in Liver Stiffness
Timepoint [5] 0 0
Screening (Day -28) and Week 24
Secondary outcome [6] 0 0
Change from Baseline in Worst Itch Numerical Scale Rating Scale (WI-NRS)
Timepoint [6] 0 0
Baseline (Day 1) and Week 24
Secondary outcome [7] 0 0
Change from Baseline in PBC-40 Itch Domain
Timepoint [7] 0 0
Baseline (Day 1) and Week 24
Secondary outcome [8] 0 0
Change from Baseline in PGIS Pruritus
Timepoint [8] 0 0
Baseline (Day 1) and Week 24
Secondary outcome [9] 0 0
Change from Baseline in PGIC Pruritus
Timepoint [9] 0 0
Baseline (Day 1) and Week 24
Secondary outcome [10] 0 0
Percentage of Participants Achieving a Biochemical Response to Setanaxib
Timepoint [10] 0 0
Baseline (Day 1) and Week 24
Secondary outcome [11] 0 0
Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs)
Timepoint [11] 0 0
Up to Week 24
Secondary outcome [12] 0 0
Percentage of Participants Who Experience Adverse Events of Special Interest (AESIs)
Timepoint [12] 0 0
Up to Week 24

Eligibility
Key inclusion criteria
- Male or female participant aged =18 years, inclusive at the time of informed consent.

- Willing and able to give written informed consent and to comply with the requirements
of the study.

- Definite or probable PBC diagnosis as demonstrated by the presence of =2 of the
following 3 diagnostic factors:

- Documented history of elevated ALP levels =1.67×ULN of the local reference range.

- Documented history of positive antimitochondrial antibodies (AMA) titer or
positive PBC-specific antibodies (anti-GP210 or anti-SP100 or antibodies against
the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex]).

- Historical liver biopsy consistent with PBC.

- Serum ALP =1.67×ULN at Screening.

- Liver stiffness measured by transient elastography (FibroScan®) of =8.8 kilopascals
(kPa) and an interquartile range over median ratio (IQR/med) of =30% at Screening, are
taken with the results expressed in kilopascals).

- Ursodeoxycholic acid (UDCA) prescriptional dose use for the past 6 months (at a stable
dose for >3 months prior to Screening) OR intolerant to UDCA (last dose of UDCA >3
months prior to Screening). Intolerance to UDCA is defined as participants unable to
tolerate the full-labelled dose of UDCA in PBC (13-15 mg/kg) due to frequently
reported gastrointestinal symptoms such as diarrhea and abdominal pain.

- For participants receiving obeticholic acid (OCA), fenofibrate, or bezafibrate
treatment for at least 6 months and stable dose for >3 months prior to Screening.

- For participants intolerant to OCA, OCA must have been discontinued >3 months prior to
Screening.

- For participants previously treated with bezafibrate or fenofibrate, and these agents
were discontinued prior to screening, they must have been discontinued >3 months prior
to Screening.

- Female participants of childbearing potential must use a highly effective method of
contraception to prevent pregnancy for =4 weeks before Randomization and must agree to
continue strict contraception up to 90 days after the last dose of investigational
medicinal product (IMP).

- For the purposes of this trial, women of childbearing potential are defined as
"Fertile, following menarche and until becoming postmenopausal unless permanently
sterile. Permanent sterilization methods include hysterectomy, bilateral
salpingectomy and bilateral oophorectomy."

- Postmenopausal state is defined as no menses for 12 months without an alternative
medical cause. In female participants who are not using hormonal contraception or
hormonal replacement therapy but with suspected menopause and less than 12 months
of amenorrhea, a high follicle stimulating hormone (FSH) level in the
postmenopausal range will be required at Screening to confirm a postmenopausal
state. Confirmation with more than one FSH measurement is required.

- Highly effective contraception is defined as methods that can achieve a failure
rate of less than 1% per year when used consistently and correctly. These methods
are:

- Combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation (oral, intravaginal, or transdermal)

- Progestogen-only hormonal contraception associated with inhibition of
ovulation (oral, injectable, or implantable)

- Intrauterine device

- Intrauterine hormone-releasing system

- Bilateral tubal occlusion

- Vasectomized partner

- Sexual abstinence (refraining from heterosexual intercourse during the
entire period of risk associate with the study treatments). The reliability
of sexual abstinence needs to be evaluated in relation to the duration of
the clinical trial and the preferred and usual lifestyle of the participant.
Periodic abstinence (calendar, symptothermal, post-ovulation methods),
withdrawal (coitus interruptus), spermicides only, and lactational
amenorrhea method are not acceptable methods of contraception. Female condom
and male condom should not be used together.

- Female participants of childbearing potential must have a negative serum pregnancy
test at Screening and a negative urine pregnancy test at Baseline/Randomization before
dosing.

- Male participants with female partners of childbearing potential must be willing to
use a condom and require their partner to use a highly effective contraceptive method.
This requirement begins at the time of informed consent and ends 90 days after
receiving the last dose of IMP.

- Male participants must be willing not to donate sperm, and female study participants
must be willing not to donate eggs, from Baseline until 90 days after the last dose of
IMP.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- A positive pregnancy test or breastfeeding for female participants.

- Any historical or current hepatic decompensation event defined as variceal/portal
hypertension bleed and/or hepatic encephalopathy, spontaneous bacterial peritonitis,
ascites requiring treatment, or liver transplantation list inclusion.

- History of liver transplantation, current placement on a liver transplant list or
current model for end stage liver disease (MELD) score of =12 unless the participant
is on anticoagulant therapy, or a Child-Pugh Score of =6.

- Cirrhosis with complications, including history or presence of hepatocellular
carcinoma.

- Total bilirubin >2×ULN. In case of total bilirubin elevation >ULN the Screening serum
albumin must be within the reference range.

- Plasma alanine aminotransferase (ALT) >3×ULN and/or aspartate aminotransferase (AST)
>3×ULN.

- International normalized ratio (INR) >1.2 unless participant is on anticoagulant
therapy. One repeat blood sampling (with analysis by the central laboratory) can be
performed at the discretion of the Investigator at Screening Visit 2 for participants
who meet this exclusion criterion at Screening Visit 1. If this exclusion criterion is
not met at Screening Visit 2, the participant may be eligible for the study.

- Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2, as calculated by the
central laboratory using the chronic kidney disease-epidemiology collaboration (CKD-
EPI) equation.

- Thyroid-stimulating hormone >ULN at Screening. One repeat blood sampling (with
analysis by the central laboratory) can be performed at the discretion of the
Investigator at Screening Visit 2 for participants who meet this exclusion criterion
at Screening Visit 1. If this exclusion criterion is not met at Screening Visit 2, the
participant may be eligible for the study.

- Competing etiology for liver disease (eg, hepatitis C [unless effectively cured of
hepatitis C, with a sustained virologic response for at least 6 months prior to
Screening], active hepatitis B [HBsAg positive], nonalcoholic steatohepatitis [NASH],
alcoholic liver disease, autoimmune hepatitis, autoimmune hepatitis-PBC overlap
syndrome, primary sclerosing cholangitis, Gilbert's Syndrome).

- Medical conditions that could cause nonhepatic increases in ALP (eg, Paget's disease).

- Known history of human immunodeficiency virus (HIV) infection.

- Surgery (eg, stomach bypass) or medical condition that might significantly affect
absorption of medicines (as judged by the Investigator).

- Positive urine drug screen (if not due to prescriptional use of a concomitant
medication, as confirmed by the Investigator) at Screening. Participants on stable
methadone or buprenorphine maintenance treatment for at least 6 months prior to
Screening Visit 1 may be included in the study. Medicinal cannabis and cannabidiol
products are not exclusionary and may be allowed if the prescription and diagnosis are
reviewed and approved by the Investigator.

- Participants receiving prohibited medications within 3 months of Screening Visit 1.

- Treatment with any investigational agent within 12 weeks of Screening Visit 1 or 5
half-lives of the IMP (if known) (whichever is longer) or current enrollment in an
interventional clinical trial.

- Evidence of any of the following cardiac conduction abnormalities: A QTc Fridericia
interval >450 milliseconds for males or >470 milliseconds for females, as calculated
by the central reader. Participants with a second- or third-degree atrioventricular
block are to be excluded.

- History of a malignancy within 5 years of Screening with the following exceptions:

- Adequately treated carcinoma in situ of the cervix.

- Adequately treated basal or squamous cell cancer or other localized nonmelanoma
skin cancer.

- The occurrence of any acute infection requiring systemic antibiotic therapy within the
2 weeks prior to Screening Visit 1.

- A history of bone marrow disorder including aplastic anemia, or any current marked
anemia defined as hemoglobin <10.0 g/dL.

- Prior treatment with setanaxib or participation in a previous setanaxib clinical
trial.

- Unstable cardiovascular disease.

- Presence of any laboratory abnormality or condition that, in the opinion of the
Investigator, could interfere with or compromise a participant's treatment,
assessment, or compliance with the protocol and/or study procedures.

- Any other condition which, in the opinion of the Investigator, constitutes a risk or
contraindication for the participation of the participant in the study, or that could
interfere with the study objectives, conduct, or evaluation.

- Hypersensitivity or intolerance to setanaxib or to any of its excipients or placebo
compounds.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/02/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
6/07/2024
Actual
Sample size
Target
Accrual to date
Final
76
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
John Hunter Hospital - New Lambton Heights
Recruitment hospital [3] 0 0
Mater Misericordiae - Hospital Brisbane - South Brisbane
Recruitment hospital [4] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [5] 0 0
Eastern Health - Australia - Box Hill
Recruitment hospital [6] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [7] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [8] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [9] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [10] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5042 - Bedford Park
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
6150 - Murdoch
Recruitment postcode(s) [8] 0 0
2747 - Kingswood
Recruitment postcode(s) [9] 0 0
2170 - Liverpool
Recruitment postcode(s) [10] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
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Florida
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Illinois
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Iowa
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United States of America
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Kansas
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Louisiana
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United States of America
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Michigan
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United States of America
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Mississippi
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New York
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North Carolina
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Ohio
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Pennsylvania
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South Dakota
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Tennessee
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Texas
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United States of America
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Utah
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United States of America
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Wisconsin
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Austria
State/province [19] 0 0
Oberösterreich
Country [20] 0 0
Austria
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Styria
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Austria
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Tyrol
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Belgium
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Brussels
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Belgium
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Flemish Brabant
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Belgium
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Oost-Vlaanderen
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Canada
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Alberta
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Canada
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Nova Scotia
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Canada
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Ontario
Country [28] 0 0
Canada
State/province [28] 0 0
Quebec
Country [29] 0 0
Canada
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Brampton
Country [30] 0 0
Czechia
State/province [30] 0 0
Prague
Country [31] 0 0
Czechia
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Hradec Králové
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France
State/province [32] 0 0
Hauts-de-France
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Ile-de-France
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Isère
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Limousin
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Lorraine
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Occitanie
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Pays De La Loire
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France
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Picardie
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France
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Rhone-alpes
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France
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Lille
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France
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Marseille
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France
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Nice
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France
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Paris
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Germany
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Bayern
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Germany
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Hessen
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Germany
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Niedersachsen
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Germany
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Sachsen
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Germany
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Homburg
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Greece
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Heraklion
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Greece
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Larissa
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Hungary
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Budapest
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Israel
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Haifa District
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Israel
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Northern District
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Israel
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Southern District
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Israel
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Tel Aviv
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Israel
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Haifa
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Israel
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Jerusalem
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Italy
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Milano
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Italy
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Milan
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Italy
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Monza And Brianza
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Italy
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Ancona
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Italy
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Messina
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Italy
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Napoli
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Italy
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Novara
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New Zealand
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Auckland
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New Zealand
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Wellington
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New Zealand
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Dunedin
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New Zealand
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Hamilton
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Poland
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Bytom
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Poland
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Myslowice
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Poland
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Wroclaw
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Spain
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Barcelona
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Spain
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Santa Cruz De Tenerife
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Spain
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Alicante
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Spain
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Almería
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Spain
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Córdoba
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Madrid
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Spain
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Málaga
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Spain
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Santiago
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Spain
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Sevilla
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Spain
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València
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Spain
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Zaragoza
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Sweden
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Uppsala
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Switzerland
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Ticino
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Switzerland
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Sankt Gallen
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United Kingdom
State/province [87] 0 0
England
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Scotland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Calliditas Therapeutics Suisse SA
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to evaluate the effect of setanaxib on alkaline
phosphatase (ALP) at Week 24 in participants with PBC and with elevated liver stiffness and
intolerance or inadequate response to ursodeoxycholic acid (UDCA).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05014672
Trial related presentations / publications
Public notes

Contacts
Principal investigator
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Address 0 0
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
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Contact person for scientific queries