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Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis (PSC-Phase 2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02943460
Recruitment Status : Active, not recruiting
First Posted : October 24, 2016
Results First Posted : March 12, 2019
Last Update Posted : July 30, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Primary Sclerosing Cholangitis
Interventions Drug: Cilofexor
Drug: Placebo to match Cilofexor
Enrollment 52
Recruitment Details Participants were enrolled at study sites in North America and Europe. The first participant was screened on 29 November 2016. The last visit in the Blinded Study phase occurred on 28 February 2018.
Pre-assignment Details 105 participants were screened.
Arm/Group Title GS-9674 100 mg GS-9674 30 mg Placebo
Hide Arm/Group Description

Blinded Study Phase: GS-9674 100 mg tablet + placebo to match GS-9674 30 mg tablet once daily for 12 weeks

Open Label Extension Phase: GS-9674 100 mg tablet once daily for an additional 96 weeks

Blinded Study Phase: GS-9674 30 mg tablet + placebo to match GS-9674 100 mg tablet once daily for 12 weeks

Open Label Extension Phase: GS-9674 100 mg tablet once daily for an additional 96 weeks

Blinded Study Phase: Placebo to match GS-9674 30 mg tablet + placebo to match GS-9674 100 mg tablet once daily for 12 weeks

Open Label Extension Phase: GS-9674 100 mg tablet once daily for an additional 96 weeks

Period Title: Blinded Study
Started 22 20 10
Completed 19 19 10 [1]
Not Completed 3 1 0
Reason Not Completed
Adverse Event             3             0             0
Withdrew Consent             0             1             0
[1]
1 participant discontinued from study drug in the Blinded Phase, but did not discontinue the study.
Period Title: Open Label Extension (OLE)
Started 19 18 [1] 9 [2]
Completed 0 0 0
Not Completed 19 18 9
Reason Not Completed
Adverse Event             0             2             1
Withdrew Consent             1             1             0
Investigator's Discretion             0             1             0
Still in Open Label Extension Phase             18             14             8
[1]
1 participant completed the Blinded Study Phase, but did not continue in the OLE Phase.
[2]
1 participant who discontinued study drug in the Blinded Phase did not enter the OLE Phase.
Arm/Group Title GS-9674 100 mg GS-9674 30 mg Placebo Total
Hide Arm/Group Description

Blinded Study Phase: GS-9674 100 mg tablet + placebo to match GS-9674 30 mg tablet once daily for 12 weeks

Open Label Extension Phase: GS-9674 100 mg tablet once daily for an additional 96 weeks

Blinded Study Phase: GS-9674 30 mg tablet + placebo to match GS-9674 100 mg tablet once daily for 12 weeks

Open Label Extension Phase: GS-9674 100 mg tablet once daily for an additional 96 weeks

Blinded Study Phase: Placebo to match GS-9674 30 mg tablet + placebo to match GS-9674 100 mg tablet once daily for 12 weeks

Open Label Extension Phase: GS-9674 100 mg tablet once daily for an additional 96 weeks

Total of all reporting groups
Overall Number of Baseline Participants 22 20 10 52
Hide Baseline Analysis Population Description
Safety Analysis Set included all participants who took at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 20 participants 10 participants 52 participants
42  (8.6) 46  (12.1) 42  (10.9) 43  (10.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 10 participants 52 participants
Female
11
  50.0%
6
  30.0%
5
  50.0%
22
  42.3%
Male
11
  50.0%
14
  70.0%
5
  50.0%
30
  57.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 10 participants 52 participants
Hispanic or Latino
0
   0.0%
3
  15.0%
0
   0.0%
3
   5.8%
Not Hispanic or Latino
21
  95.5%
17
  85.0%
9
  90.0%
47
  90.4%
Unknown or Not Reported
1
   4.5%
0
   0.0%
1
  10.0%
2
   3.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 10 participants 52 participants
Asian
0
   0.0%
2
  10.0%
1
  10.0%
3
   5.8%
Black or African American
4
  18.2%
3
  15.0%
1
  10.0%
8
  15.4%
White
17
  77.3%
15
  75.0%
7
  70.0%
39
  75.0%
Not Permitted
0
   0.0%
0
   0.0%
1
  10.0%
1
   1.9%
Other
1
   4.5%
0
   0.0%
0
   0.0%
1
   1.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 10 participants 52 participants
Canada 4 2 2 8
Austria 1 0 0 1
United States 12 17 7 36
United Kingdom 5 1 1 7
1.Primary Outcome
Title Percentage of Participants Experiencing Treatment-Emergent Adverse Events During the Blinded Phase
Hide Description Treatment-emergent adverse events occurring during the Blinded Phase were defined as 1 or both of the following: 1) Any adverse events (AEs) with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug in the Blinded Phase (and before the first dosing date in the Open Label Extension (OLE) Phase), or 2) Any AEs leading to premature discontinuation of study drug in the Blinded Phase.
Time Frame Up to 12 weeks plus 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set included all participants who took at least 1 dose of study drug.
Arm/Group Title GS-9674 100 mg GS-9674 30 mg Placebo
Hide Arm/Group Description:
GS-9674 100 mg tablet + placebo to match GS-9674 30 mg tablet once daily for 12 weeks
GS-9674 30 mg tablet + placebo to match GS-9674 100 mg tablet once daily for 12 weeks
Placebo to match GS-9674 30 mg tablet + placebo to match GS-9674 100 mg tablet once daily for 12 weeks
Overall Number of Participants Analyzed 22 20 10
Measure Type: Number
Unit of Measure: percentage of participants
81.8 65.0 100.0
2.Primary Outcome
Title Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events During the Blinded Phase
Hide Description A serious adverse event was defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction.
Time Frame Up to 12 weeks plus 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set were analyzed.
Arm/Group Title GS-9674 100 mg GS-9674 30 mg Placebo
Hide Arm/Group Description:
GS-9674 100 mg tablet + placebo to match GS-9674 30 mg tablet once daily for 12 weeks
GS-9674 30 mg tablet + placebo to match GS-9674 100 mg tablet once daily for 12 weeks
Placebo to match GS-9674 30 mg tablet + placebo to match GS-9674 100 mg tablet once daily for 12 weeks
Overall Number of Participants Analyzed 22 20 10
Measure Type: Number
Unit of Measure: percentage of participants
13.6 0 0
3.Primary Outcome
Title Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities During the Blinded Phase
Hide Description Treatment-emergent laboratory abnormalities occurring during the Blinded Phase were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug in the Blinded Phase plus 30 days. The Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 was used for assigning toxicity grades (0 to 4, with higher grades indicating more severity).
Time Frame Up to 12 weeks plus 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set were analyzed.
Arm/Group Title GS-9674 100 mg GS-9674 30 mg Placebo
Hide Arm/Group Description:
GS-9674 100 mg tablet + placebo to match GS-9674 30 mg tablet once daily for 12 weeks
GS-9674 30 mg tablet + placebo to match GS-9674 100 mg tablet once daily for 12 weeks
Placebo to match GS-9674 30 mg tablet + placebo to match GS-9674 100 mg tablet once daily for 12 weeks
Overall Number of Participants Analyzed 22 20 10
Measure Type: Number
Unit of Measure: percentage of participants
Any Grade 1 or Higher 90.9 85.0 100.0
Grade 1 22.7 25.0 10.0
Grade 2 36.4 35.0 60.0
Grade 3 27.3 20.0 30.0
Grade 4 4.5 5.0 0
Time Frame Up to the Week 12 Data Cut
Adverse Event Reporting Description Safety Analysis Set included all participants who took at least 1 dose of study drug.
 
Arm/Group Title GS-9674 100 mg (Blinded Phase) GS-9674 30 mg (Blinded Phase) Placebo (Blinded Phase) GS-9674 100 mg (Open Label Phase)
Hide Arm/Group Description GS-9674 100 mg tablet + placebo to match GS-9674 30 mg tablet once daily for 12 weeks GS-9674 30 mg tablet + placebo to match GS-9674 100 mg tablet once daily for 12 weeks Placebo to match GS-9674 30 mg tablet + placebo to match GS-9674 100 mg tablet once daily for 12 weeks Following the Blinded Phase, eligible participants received GS-9674 100 mg tablet once daily for an additional 96 weeks.
All-Cause Mortality
GS-9674 100 mg (Blinded Phase) GS-9674 30 mg (Blinded Phase) Placebo (Blinded Phase) GS-9674 100 mg (Open Label Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)   0/20 (0.00%)   0/10 (0.00%)   0/46 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
GS-9674 100 mg (Blinded Phase) GS-9674 30 mg (Blinded Phase) Placebo (Blinded Phase) GS-9674 100 mg (Open Label Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/22 (13.64%)   0/20 (0.00%)   0/10 (0.00%)   2/46 (4.35%) 
Gastrointestinal disorders         
Abdominal pain  1  0/22 (0.00%)  0/20 (0.00%)  0/10 (0.00%)  1/46 (2.17%) 
Diarrhoea  1  1/22 (4.55%)  0/20 (0.00%)  0/10 (0.00%)  0/46 (0.00%) 
General disorders         
Chest pain  1  0/22 (0.00%)  0/20 (0.00%)  0/10 (0.00%)  1/46 (2.17%) 
Infections and infestations         
Sepsis  1  0/22 (0.00%)  0/20 (0.00%)  0/10 (0.00%)  1/46 (2.17%) 
Injury, poisoning and procedural complications         
Rib fracture  1  1/22 (4.55%)  0/20 (0.00%)  0/10 (0.00%)  0/46 (0.00%) 
Metabolism and nutrition disorders         
Dehydration  1  1/22 (4.55%)  0/20 (0.00%)  0/10 (0.00%)  0/46 (0.00%) 
Renal and urinary disorders         
Acute kidney injury  1  1/22 (4.55%)  0/20 (0.00%)  0/10 (0.00%)  0/46 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
GS-9674 100 mg (Blinded Phase) GS-9674 30 mg (Blinded Phase) Placebo (Blinded Phase) GS-9674 100 mg (Open Label Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   18/22 (81.82%)   13/20 (65.00%)   10/10 (100.00%)   28/46 (60.87%) 
Eye disorders         
Blepharitis  1  0/22 (0.00%)  1/20 (5.00%)  0/10 (0.00%)  0/46 (0.00%) 
Gastrointestinal disorders         
Abdominal discomfort  1  1/22 (4.55%)  0/20 (0.00%)  1/10 (10.00%)  1/46 (2.17%) 
Abdominal distension  1  2/22 (9.09%)  0/20 (0.00%)  1/10 (10.00%)  1/46 (2.17%) 
Abdominal pain  1  1/22 (4.55%)  0/20 (0.00%)  1/10 (10.00%)  4/46 (8.70%) 
Abdominal pain upper  1  3/22 (13.64%)  2/20 (10.00%)  1/10 (10.00%)  3/46 (6.52%) 
Constipation  1  2/22 (9.09%)  0/20 (0.00%)  0/10 (0.00%)  0/46 (0.00%) 
Diarrhoea  1  1/22 (4.55%)  1/20 (5.00%)  0/10 (0.00%)  3/46 (6.52%) 
Dyspepsia  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Faeces pale  1  0/22 (0.00%)  1/20 (5.00%)  0/10 (0.00%)  0/46 (0.00%) 
Flatulence  1  0/22 (0.00%)  1/20 (5.00%)  0/10 (0.00%)  1/46 (2.17%) 
Nausea  1  0/22 (0.00%)  1/20 (5.00%)  3/10 (30.00%)  4/46 (8.70%) 
Noninfective sialoadenitis  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Pouchitis  1  0/22 (0.00%)  1/20 (5.00%)  0/10 (0.00%)  0/46 (0.00%) 
Tongue disorder  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Vomiting  1  0/22 (0.00%)  1/20 (5.00%)  1/10 (10.00%)  1/46 (2.17%) 
General disorders         
Chills  1  0/22 (0.00%)  1/20 (5.00%)  0/10 (0.00%)  1/46 (2.17%) 
Fatigue  1  3/22 (13.64%)  2/20 (10.00%)  2/10 (20.00%)  3/46 (6.52%) 
Pain  1  0/22 (0.00%)  1/20 (5.00%)  0/10 (0.00%)  0/46 (0.00%) 
Pyrexia  1  1/22 (4.55%)  2/20 (10.00%)  0/10 (0.00%)  2/46 (4.35%) 
Hepatobiliary disorders         
Hepatitis acute  1  0/22 (0.00%)  1/20 (5.00%)  0/10 (0.00%)  0/46 (0.00%) 
Hepatitis cholestatic  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Infections and infestations         
Conjunctivitis  1  1/22 (4.55%)  1/20 (5.00%)  0/10 (0.00%)  0/46 (0.00%) 
Influenza  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Nasopharyngitis  1  5/22 (22.73%)  5/20 (25.00%)  2/10 (20.00%)  7/46 (15.22%) 
Respiratory tract infection  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Sinusitis  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  1/46 (2.17%) 
Upper respiratory tract infection  1  2/22 (9.09%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Viral infection  1  2/22 (9.09%)  0/20 (0.00%)  0/10 (0.00%)  1/46 (2.17%) 
Injury, poisoning and procedural complications         
Stoma site pain  1  0/22 (0.00%)  1/20 (5.00%)  0/10 (0.00%)  0/46 (0.00%) 
Investigations         
Alanine aminotransferase increased  1  1/22 (4.55%)  0/20 (0.00%)  2/10 (20.00%)  0/46 (0.00%) 
Aspartate aminotransferase increased  1  0/22 (0.00%)  0/20 (0.00%)  2/10 (20.00%)  1/46 (2.17%) 
Blood alkaline phosphatase increased  1  2/22 (9.09%)  0/20 (0.00%)  1/10 (10.00%)  1/46 (2.17%) 
Blood bilirubin increased  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  2/46 (4.35%) 
Electrocardiogram abnormal  1  2/22 (9.09%)  0/20 (0.00%)  0/10 (0.00%)  0/46 (0.00%) 
Gamma-glutamyltransferase increased  1  1/22 (4.55%)  1/20 (5.00%)  0/10 (0.00%)  0/46 (0.00%) 
Hepatic enzyme increased  1  0/22 (0.00%)  1/20 (5.00%)  0/10 (0.00%)  1/46 (2.17%) 
Metabolism and nutrition disorders         
Decreased appetite  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  1/46 (2.17%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  1/46 (2.17%) 
Back pain  1  1/22 (4.55%)  2/20 (10.00%)  0/10 (0.00%)  2/46 (4.35%) 
Flank pain  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Muscle spasms  1  1/22 (4.55%)  2/20 (10.00%)  0/10 (0.00%)  0/46 (0.00%) 
Pain in extremity  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Benign neoplasm of skin  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Haemangioma  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Melanocytic naevus  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Seborrhoeic keratosis  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Nervous system disorders         
Dizziness  1  2/22 (9.09%)  1/20 (5.00%)  0/10 (0.00%)  1/46 (2.17%) 
Headache  1  1/22 (4.55%)  4/20 (20.00%)  2/10 (20.00%)  3/46 (6.52%) 
Paraesthesia  1  1/22 (4.55%)  1/20 (5.00%)  0/10 (0.00%)  1/46 (2.17%) 
Renal and urinary disorders         
Chromaturia  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Reproductive system and breast disorders         
Erectile dysfunction  1  0/22 (0.00%)  1/20 (5.00%)  0/10 (0.00%)  0/46 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Oropharyngeal pain  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  1/46 (2.17%) 
Skin and subcutaneous tissue disorders         
Dermal cyst  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  0/46 (0.00%) 
Dermatitis  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  1/46 (2.17%) 
Pruritus  1  7/22 (31.82%)  5/20 (25.00%)  6/10 (60.00%)  12/46 (26.09%) 
Rash  1  1/22 (4.55%)  0/20 (0.00%)  1/10 (10.00%)  2/46 (4.35%) 
Rash pruritic  1  0/22 (0.00%)  1/20 (5.00%)  0/10 (0.00%)  0/46 (0.00%) 
Urticaria  1  0/22 (0.00%)  0/20 (0.00%)  1/10 (10.00%)  1/46 (2.17%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gilead Clinical Study Information Center
Organization: Gilead Sciences
Phone: 1-833-445-3230 (GILEAD-0)
EMail: GileadClinicalTrials@gilead.com
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02943460     History of Changes
Other Study ID Numbers: GS-US-428-4025
2016-002442-23 ( EudraCT Number )
First Submitted: June 13, 2016
First Posted: October 24, 2016
Results First Submitted: February 21, 2019
Results First Posted: March 12, 2019
Last Update Posted: July 30, 2019