Primary Biliary CholangitisPhase 2PBC-Phase 2NCT02943447

Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Biliary Cholangitis Without Cirrhosis

A Phase 2 study testing Cilofexor in people with Primary Biliary Cholangitis, run by Gilead Sciences at 25 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The primary objective of this study is to evaluate the safety and tolerability of cilofexor in adults with primary biliary cholangitis (PBC). Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Primary Biliary Cholangitis
What is being tested?: Cilofexor
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 71 participants
Where: 25 sitesin 4 countries
Study dates: 1 Dec 2016to 4 Sep 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Meets all of the following conditions
Definite or probable PBC as defined by at least 2 of the 3 following criteria:
Serum alkaline phosphatase (ALP) > the upper limit of normal (ULN)
Presence of anti-mitochondrial antibodies (AMA) in serum (≥ 1:40 on immunofluorescence)
Liver histological findings consistent with PBC including nonsuppurative, destructive cholangitis affecting mainly the interlobular bile and septal bile ducts
Serum ALP > 1.67 x ULN and/or total bilirubin >ULN but ≤ 2 x ULN
Ursodeoxycholic acid (UDCA) use at a stable dose for at least 12 months or intolerant of UDCA with no UDCA use for at least 12 months before screening
Screening FibroSURE/FibroTest® < 0.75 unless a historical liver biopsy within 12 months of screening does not reveal cirrhosis. In adults with Gilbert's syndrome or hemolysis, FibroSURE/FibroTest will be calculated using direct bilirubin instead of total bilirubin.

Who cannot join

Alanine aminotransferase (ALT) > 5 x ULN
Total bilirubin > 2 x ULN
International normalized ratio (INR) > 1.2 unless on anticoagulant therapy
Other causes of liver disease including viral, metabolic, alcoholic, and other autoimmune conditions. Participants with hepatic steatosis may be included if there is no evidence of nonalcoholic steatohepatitis (NASH) in the opinion of the investigator or on liver biopsy.
Use of fibrates or obeticholic acid within 3 months prior to screening through the end of treatment
Cirrhosis of the liver as defined by any of the following:

Show all 10Show fewer

Historical liver biopsy demonstrating cirrhosis (eg, Ludwig stage 4 or Ishak stage ≥ 5)
History of decompensated liver disease, including ascites, hepatic encephalopathy or variceal bleeding
Liver stiffness > 16.9 kPa by FibroScan®
Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

25 sites in 4 countries.

Country

City, postcode or hospital

25 sites in 4 countries

United States13 sites

Study site
Arlington, Texas, 76012
Study site
Aurora, Colorado, 80045
Study site
Charlottesville, Virginia, 22908
Study site
Dallas, Texas, 75203
Study site
Dallas, Texas, 75246
Study site
Houston, Texas, 77030
Study site
Lakewood Rch, Florida, 34211
Study site
Marietta, Georgia, 30060
Study site
Miami, Florida, 33136
Study site
Newport News, Virginia, 23602
Study site
Sacramento, California, 95817
Study site
Saint Paul, Minnesota, 55114
Study site
Seattle, Washington, 98104

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Canada6 sites

Study site
Calgary, Alberta, T2N 4Z6
Study site
Toronto, Ontario, M5G 2C4
Study site
Vancouver, British Columbia, V5Z 1M9
Study site
Vancouver, British Columbia, V6Z 2K5
Study site
Vaughan, Ontario, L4L 4Y7
Study site
Winnipeg, Manitoba, R3E 0T6

Other trials in Canada

United Kingdom4 sites

Study site
Birmingham, England, B215 2GW
Study site
London, England, NW3 2QG
Study site
London, England, SE5 9RS
Study site
Norwich, England, NR4 7UY

Other trials in United Kingdom

Austria2 sites

Study site
Graz, Styria, 8036
Study site
Vienna, State of Vienna, 1090

Other trials in Austria

About this study

Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Subjects With Primary Biliary Cholangitis Without Cirrhosis

The primary objective of this study is to evaluate the safety and tolerability of cilofexor in adults with primary biliary cholangitis (PBC).

Conditions: Primary Biliary Cholangitis
Being tested: Cilofexor, Placebo to match cilofexor
Medical subject headings: Liver Cirrhosis, Biliary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CilofexorDrug
Also called GS-9674
Tablet(s) administered orally once daily, with food
Placebo to match cilofexorDrug
Tablet(s) administered orally once daily, with food

Study groups in NCT02943447
Study group	Role	What they receive
Cilofexor 30 mg (Blinded Study Phase)	Experimental	Cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks. Receives: Drug: Cilofexor; Drug: Placebo to match cilofexor
Cilofexor 100 mg (Blinded Study Phase)	Experimental	Cilofexor 100 mg + placebo to match cilofexor 30 mg for 12 weeks. Receives: Drug: Cilofexor; Drug: Placebo to match cilofexor
Placebo (Blinded Study Phase)	Placebo comparator	Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks. Receives: Drug: Placebo to match cilofexor
Cilofexor (Open Label Extension Phase)	Experimental	Following the Blinded Study Phase, eligible participants may have the option to receive open-label cilofexor 100 mg for an additional 96 weeks. Receives: Drug: Cilofexor

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) in the Blinded Study Phase
Measured: First dose date up to Week 12 + 30 days
Percentage of Participants Experiencing TEAEs and TESAEs in the Open-Label Extension (OLE) Phase
Measured: First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days
Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the Blinded Study Phase
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.
Measured: First dose date up to Week 12 + 30 days
Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the OLE Phase
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.
Measured: First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Dec 20164 Sep 2019

First posted24 Oct 2016 (estimated)
Study start1 Dec 2016
Primary completion4 Sep 2019
Study completion4 Sep 2019

Why it stopped: The study was terminated because of the availability of alternate therapies for primary biliary cholangitis (PBC).

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Primary Biliary CholangitisStudies of the same condition, open and under way.
More trials run by Gilead SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 71 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02943447
Sponsor's protocol ID: GS-US-427-4024
Other IDs: 2016-002443-42, 2016
Acronym: PBC-Phase 2
Status last verified: Sep 2020
First submitted: 13 Jun 2016
Last updated: 22 Sep 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Kowdley KV, Minuk GY, Pagadala MR, Gulamhusein A, Swain MG, Neff GW, et al. The Nonsteroidal Farnesoid X Receptor (FXR) Agonist Cilofexor Improves Liver Biochemistry in Patients with Primary Biliary Cholangitis (PBC): A Phase 2, Randomized, Placebo-Controlled Trial [Abstract 45]. Hepatology AASLD Abstracts 2019;70 (Suppl 1):31A-2A.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 3
Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC)
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Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis
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FIREFLY Trial: Fenofibrate Intervention---Randomized Evaluation in First-Line PBC Therapy
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Fenofibrate for Patients With Primary Biliary Cirrhosis Who Had An Inadequate Response to Ursodeoxycholic Acid
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Study at a glance

From the registry record, last updated by the sponsor on 22 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Subjects With Primary Biliary Cholangitis Without Cirrhosis
ClinicalTrials.gov ID: NCT02943447
Acronym / sponsor ID: PBC-Phase 2 / GS-US-427-4024
Conditions: Primary Biliary Cholangitis
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated because of the availability of alternate therapies for primary biliary cholangitis (PBC).
Enrolment: 71 participants (actual)
Lead sponsor: Gilead SciencesIndustry (pharma, biotech, devices)
Study start: 1 Dec 2016 (actual)
Primary completion: 4 Sep 2019 (actual)
Study completion: 4 Sep 2019 (actual)
First posted: 24 Oct 2016 (estimated)
Results: Posted 13 Jan 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The primary objective of this study is to evaluate the safety and tolerability of cilofexor in adults with primary biliary cholangitis (PBC).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Cilofexor 30 mg (Blinded Study Phase)	Experimental	Drug: Cilofexor, Drug: Placebo to match cilofexorCilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.
Cilofexor 100 mg (Blinded Study Phase)	Experimental	Drug: Cilofexor, Drug: Placebo to match cilofexorCilofexor 100 mg + placebo to match cilofexor 30 mg for 12 weeks.
Placebo (Blinded Study Phase)	Placebo comparator	Drug: Placebo to match cilofexorPlacebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.
Cilofexor (Open Label Extension Phase)	Experimental	Drug: CilofexorFollowing the Blinded Study Phase, eligible participants may have the option to receive open-label cilofexor 100 mg for an additional 96 weeks.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Meets all of the following conditions
Screening FibroSURE/FibroTest® < 0.75 unless a historical liver biopsy within 12 months of screening does not reveal cirrhosis. In adults with Gilbert's syndrome or hemolysis, FibroSURE/FibroTest will be calculated using direct bilirubin instead of total bilirubin.

Key exclusion criteria (10 listed)

Alanine aminotransferase (ALT) > 5 x ULN
Total bilirubin > 2 x ULN
International normalized ratio (INR) > 1.2 unless on anticoagulant therapy
Other causes of liver disease including viral, metabolic, alcoholic, and other autoimmune conditions. Participants with hepatic steatosis may be included if there is no evidence of nonalcoholic steatohepatitis (NASH) in the opinion of the investigator or on liver biopsy.
Use of fibrates or obeticholic acid within 3 months prior to screening through the end of treatment

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CilofexorAlso: GS-9674Tablet(s) administered orally once daily, with food	Drug	Cilofexor (Open Label Extension Phase), Cilofexor 100 mg (Blinded Study Phase), Cilofexor 30 mg (Blinded Study Phase)
Placebo to match cilofexorTablet(s) administered orally once daily, with food	Drug	Cilofexor 100 mg (Blinded Study Phase), Cilofexor 30 mg (Blinded Study Phase), Placebo (Blinded Study Phase)

Primary outcome

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) in the Blinded Study Phase
Time frame: First dose date up to Week 12 + 30 days
Percentage of Participants Experiencing TEAEs and TESAEs in the Open-Label Extension (OLE) Phase
Time frame: First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days
Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the Blinded Study Phase
Time frame: First dose date up to Week 12 + 30 days
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.
Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the OLE Phase
Time frame: First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.

Results and safety

Results posted to the registry on 13 Jan 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cilofexor 100 mg	28	23
Cilofexor 30 mg	30	28
Placebo	13	12

Primary outcome: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) in the Blinded Study Phase

Time frame: First dose date up to Week 12 + 30 days. Number. Unit: percentage of participants

Measure	Blinded Study Phase: Cilofexor 100 mg n = 28	Blinded Study Phase: Cilofexor 30 mg n = 30	Blinded Study Phase: Placebo n = 13
TEAEs	89.3	76.7	84.6
TESAEs	0	3.3	0

Population analysed: The Safety Analysis Set included all participants who took at least 1 dose of study drug.

Primary outcome: Percentage of Participants Experiencing TEAEs and TESAEs in the Open-Label Extension (OLE) Phase

Time frame: First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days. Number. Unit: percentage of participants

Measure	OLE Phase: From Cilofexor 100 mg n = 23	OLE Phase: From Cilofexor 30 mg n = 28	OLE Phase: From Placebo n = 12
TEAEs	95.7	89.3	100.0
TESAEs	4.3	0	0

Population analysed: The OLE Analysis Set included all participants who took at least 1 dose of study drug in the OLE Phase.

Primary outcome: Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the Blinded Study Phase

Time frame: First dose date up to Week 12 + 30 days. Number. Unit: percentage of participants

Measure	Blinded Study Phase: Cilofexor 100 mg n = 28	Blinded Study Phase: Cilofexor 30 mg n = 30	Blinded Study Phase: Placebo n = 13
Any Graded Laboratory Abnormality	85.7	86.7	92.3
Grade 4 or above Laboratory Abnormalities	0	3.3	0

Population analysed: Participants in the Safety Analysis Set were analyzed.

Primary outcome: Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the OLE Phase

Time frame: First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days. Number. Unit: percentage of participants

Measure	OLE Phase: From Cilofexor 100 mg n = 23	OLE Phase: From Cilofexor 30 mg n = 28	OLE Phase: From Placebo n = 12
Any Graded Laboratory Abnormality	91.3	96.4	100.0
Grade 4 or above Laboratory Abnormalities	0	0	0

Population analysed: Participants in the OLE Analysis Set were analyzed.

Adverse events

Time frame: Blinded Study Phase: First dose date up to Week 12 + 30 days; Open-label Extension (OLE) Phase: First dose date in the OLE Phase up to last dose date (Maximum: 97.4 weeks) + 30 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Blinded Study Phase: Cilofexor 100 mg	0 of 28 (0%)	21 of 28 (75%)	0 of 28
Blinded Study Phase: Cilofexor 30 mg	1 of 30 (3.3%)	18 of 30 (60%)	0 of 30
Blinded Study Phase: Placebo	0 of 13 (0%)	11 of 13 (84.6%)	0 of 13
OLE Phase: From Cilofexor 100 mg	1 of 23 (4.3%)	20 of 23 (87%)	0 of 23
OLE Phase: From Cilofexor 30 mg	0 of 28 (0%)	25 of 28 (89.3%)	0 of 28
OLE Phase: From Placebo	0 of 12 (0%)	12 of 12 (100%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publicationKowdley KV, Minuk GY, Pagadala MR, Gulamhusein A, Swain MG, Neff GW, et al. The Nonsteroidal Farnesoid X Receptor (FXR) Agonist Cilofexor Improves Liver Biochemistry in Patients with Primary Biliary Cholangitis (PBC): A Phase 2, Randomized, Placebo-Controlled Trial [Abstract 45]. Hepatology AASLD Abstracts 2019;70 (Suppl 1):31A-2A.
Individual participant dataSharing planned: No

Related trials for Primary Biliary Cholangitis

Active, not recruitingPhase 3
Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC)
Primary Biliary Cirrhosis
RecruitingPhase 3
Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis
Primary Biliary Cholangitis
RecruitingPhase 3
FIREFLY Trial: Fenofibrate Intervention---Randomized Evaluation in First-Line PBC Therapy
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gilead Study Director study director

Gilead Sciences

25 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cilofexor in people with Primary Biliary Cholangitis, run by Gilead Sciences at 25 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, Canada, United Kingdom, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) in the Blinded Study Phase (time frame: First dose date up to Week 12 + 30 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02943447, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2020.