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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03890120




Registration number
NCT03890120
Ethics application status
Date submitted
25/03/2019
Date registered
26/03/2019
Date last updated
29/11/2023

Titles & IDs
Public title
Study of Cilofexor in Adults With Primary Sclerosing Cholangitis
Scientific title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of Cilofexor in Non-Cirrhotic Subjects With Primary Sclerosing Cholangitis
Secondary ID [1] 0 0
2019-000204-14
Secondary ID [2] 0 0
GS-US-428-4194
Universal Trial Number (UTN)
Trial acronym
PRIMIS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Sclerosing Cholangitis 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 - Cilofexor
Treatment: Drugs - Placebo

Experimental: Cilofexor 100 mg (Blinded Phase) - Participants received cilofexor 100 mg tablet, orally, once daily for up to 100.3 weeks.

Placebo comparator: Placebo (Blinded Phase) - Participants received placebo to match cilofexor 100 mg tablet, orally, once daily for up to 98.1 weeks.

Experimental: Cilofexor From Cilofexor 100 mg (OLE Phase) - Participants who received cilofexor in blinded phase and had entered the open-label extension (OLE) phase received open-label cilofexor 100 mg tablet, orally, once daily for up to 44.7 weeks.

Experimental: Cilofexor From Placebo (OLE Phase) - Participants who received placebo in blinded phase and had entered the OLE phase received open-label cilofexor 100 mg tablet, orally, once daily for up to 45.0 weeks.


Treatment: Drugs: Cilofexor
100 mg tablet administered orally once daily

Treatment: Drugs: Placebo
Tablet administered orally once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Progression of Liver Fibrosis at Blinded Phase Week 96
Timepoint [1] 0 0
Blinded Phase Week 96
Secondary outcome [1] 0 0
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) in The Blinded Phase
Timepoint [1] 0 0
First dose date in the Blinded Phase up to 100.3 weeks plus 30 days
Secondary outcome [2] 0 0
Percentage of Participants Who Experienced TEAEs in The OLE Phase
Timepoint [2] 0 0
First dose date in the OLE Phase up to 45 weeks plus 30 days
Secondary outcome [3] 0 0
Percentage of Participants Who Experienced Treatment-emergent Serious Adverse Events (SAEs) in the Blinded Phase
Timepoint [3] 0 0
First dose date in the Blinded Phase up to 100.3 weeks plus 30 days
Secondary outcome [4] 0 0
Percentage of Participants Who Experienced Treatment-emergent SAEs in the OLE Phase
Timepoint [4] 0 0
First dose date in the OLE Phase up to 45 weeks plus 30 days
Secondary outcome [5] 0 0
Change From Baseline in Serum Concentrations of Alkaline Phosphatase (ALP) at Blinded Phase Week 96
Timepoint [5] 0 0
Baseline, Blinded Phase Week 96
Secondary outcome [6] 0 0
Change From Baseline in Serum Concentrations of Alanine Aminotransferase (ALT) at Blinded Phase Week 96
Timepoint [6] 0 0
Baseline, Blinded Phase Week 96
Secondary outcome [7] 0 0
Change From Baseline in Serum Concentrations of Fasting Total Bile Acids at Blinded Phase Week 96
Timepoint [7] 0 0
Baseline, Blinded Phase Week 96
Secondary outcome [8] 0 0
Percentage of Participants With = 25% Relative Reduction in Serum ALP Concentration From Baseline and No Worsening of Fibrosis According to the Ludwig Classification at Blinded Phase Week 96
Timepoint [8] 0 0
Baseline, Blinded Phase Week 96
Secondary outcome [9] 0 0
Percentage of Participants With Fibrosis Improvement According to the Ludwig Classification at Blinded Phase Week 96
Timepoint [9] 0 0
Blinded Phase Week 96
Secondary outcome [10] 0 0
Change From Baseline in Primary Sclerosing Cholangitis (PSC) Symptoms - Module 1 Based on Disease-specific Patient Reported Outcome (PSC-PRO) at Blinded Phase Week 96
Timepoint [10] 0 0
Baseline, Blinded Phase Week 96
Secondary outcome [11] 0 0
Change From Baseline in Enhanced Liver Fibrosis (ELF™ ) Test Score at Blinded Phase Week 96
Timepoint [11] 0 0
Baseline, Blinded Phase Week 96
Secondary outcome [12] 0 0
Change From Baseline in Liver Stiffness by FibroScan® at Blinded Phase Week 96
Timepoint [12] 0 0
Baseline, Blinded Phase Week 96

Eligibility
Key inclusion criteria
Key

* Diagnosis of large duct PSC
* Liver biopsy at screening that is deemed acceptable for interpretation and demonstrates stage F0 - F3 fibrosis in the opinion of the central reader
* Individual has the following laboratory parameters at the screening visit, as determined by the central laboratory:

* Platelet count = 150,000/mm^3
* Estimated glomerular filtration rate (eGFR) = 30 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation
* Alanine transaminase (ALT) = 8 x upper limit of the normal range (ULN)
* Total bilirubin < 2 mg/dL, unless the individual is known to have Gilbert's syndrome or hemolytic anemia
* International normalized ratio (INR) = 1.4, unless due to therapeutic anticoagulation
* Negative anti-mitochondrial antibody

Key
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Current or prior history of any of the following:

* Cirrhosis
* Liver transplantation
* Cholangiocarcinoma or hepatocellular carcinoma (HCC)
* Ascending cholangitis within 30 days of screening
* Presence of a percutaneous drain or biliary stent
* Other causes of liver disease
* Current or prior history of unstable cardiovascular disease
* Current moderate to severe inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, and indeterminate colitis)

Note: Other protocol defined Inclusion/Exclusion criteria may apply

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 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/12/2022
Sample size
Target
Accrual to date
Final
419
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
St. Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
Nepean Hospital - Penrith
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
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Coral Sea Clinical Research Institute - Mackay - Auchenflower
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Royal Brisbane and Women's Hospital - Herston
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Mater Misericordiae Ltd - South Brisbane
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Monash Health - Clayton
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Austin Health - Heidelberg
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The Alfred Hospital - Melbourne
Recruitment hospital [11] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment hospital [12] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [13] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
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2010 - Darlinghurst
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2751 - Penrith
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2145 - Westmead
Recruitment postcode(s) [5] 0 0
4066 - Auchenflower
Recruitment postcode(s) [6] 0 0
4029 - Herston
Recruitment postcode(s) [7] 0 0
4101 - South Brisbane
Recruitment postcode(s) [8] 0 0
3168 - Clayton
Recruitment postcode(s) [9] 0 0
3084 - Heidelberg
Recruitment postcode(s) [10] 0 0
3004 - Melbourne
Recruitment postcode(s) [11] 0 0
3050 - Parkville
Recruitment postcode(s) [12] 0 0
6009 - Nedlands
Recruitment postcode(s) [13] 0 0
6000 - Perth
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to evaluate whether cilofexor reduces the risk of fibrosis progression among non-cirrhotic adults with primary sclerosing cholangitis (PSC).
Trial website
https://clinicaltrials.gov/study/NCT03890120
Trial related presentations / publications
Trauner M, Chung C, Sterling K, Liu X, Lu X, Xu J, Tempany-Afdhal C, Goodman ZD, Farkkila M, Tanaka A, Trivedi P, Kowdley KV, Bowlus CL, Levy C, Myers RP. PRIMIS: design of a pivotal, randomized, phase 3 study evaluating the safety and efficacy of the nonsteroidal farnesoid X receptor agonist cilofexor in noncirrhotic patients with primary sclerosing cholangitis. BMC Gastroenterol. 2023 Mar 15;23(1):75. doi: 10.1186/s12876-023-02653-2.
Trauner M, Levy C, Tanaka A, Goodman Z, Thorburn D, et al. A Phase 3 Randomized, Double-blind, Placebo-controlled Study Evaluation the Efficacy and Safety of Cilofexor in Patients With Non-cirrhotic Patients With Primary Sclerosing Cholangitis. J Hepatol. 2023 June;78(S1):S12-S13.
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03890120