Trial Outcomes & Findings for Open Label Study to Evaluate Safety and Efficacy of LUM001 in Patients With Primary Sclerosing Cholangitis (NCT NCT02061540)
NCT ID: NCT02061540
Last Updated: 2019-03-29
Results Overview
An Adverse Event (AE) was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered to be related to the investigational drug product. TEAEs were AEs with a start date on or after the first dose of investigational product and started prior to the last dose of investigational product plus 14 days.
COMPLETED
PHASE2
27 participants
From start of study drug administration until Week 18
2019-03-29
Participant Flow
The study was conducted in 8 centers in Great Britain, Canada, and the United States between 22 April 2014 and 12 February 2016.
A total of 37 participants were screened, of them 27 participants were enrolled in the study.
Participant milestones
| Measure |
Maralixibat (LUM001)
Participants received LUM001 tablet orally once daily at a dose of 0.5 milligram (mg) during Week 1; 1 mg during Week 2; 2.5 mg during Week 3; 5 mg during Week 4; 7.5 mg during Week 5; 10 mg during Week 6 followed by stable dosing of 10 mg for 8 weeks.
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|---|---|
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Overall Study
STARTED
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27
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Overall Study
Down-Titrated on LUM001 During the Study
|
5
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Overall Study
COMPLETED
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23
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Overall Study
NOT COMPLETED
|
4
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Reasons for withdrawal
| Measure |
Maralixibat (LUM001)
Participants received LUM001 tablet orally once daily at a dose of 0.5 milligram (mg) during Week 1; 1 mg during Week 2; 2.5 mg during Week 3; 5 mg during Week 4; 7.5 mg during Week 5; 10 mg during Week 6 followed by stable dosing of 10 mg for 8 weeks.
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|---|---|
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Overall Study
Adverse Event
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2
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Overall Study
Withdrawal by Subject
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2
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Baseline Characteristics
Open Label Study to Evaluate Safety and Efficacy of LUM001 in Patients With Primary Sclerosing Cholangitis
Baseline characteristics by cohort
| Measure |
Maralixibat (LUM001)
n=27 Participants
Participants received LUM001 tablet orally once daily at a dose of 0.5 milligram (mg) during Week 1; 1 mg during Week 2; 2.5 mg during Week 3; 5 mg during Week 4; 7.5 mg during Week 5; 10 mg during Week 6 followed by stable dosing of 10 mg for 8 weeks.
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|---|---|
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Age, Continuous
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43.7 Years
STANDARD_DEVIATION 11.35 • n=5 Participants
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Sex: Female, Male
Female
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9 Participants
n=5 Participants
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Sex: Female, Male
Male
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18 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: From start of study drug administration until Week 18Population: Safety population included all participants who received at least 1 dose of the investigational product.
An Adverse Event (AE) was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered to be related to the investigational drug product. TEAEs were AEs with a start date on or after the first dose of investigational product and started prior to the last dose of investigational product plus 14 days.
Outcome measures
| Measure |
Maralixibat (LUM001) 1 mg
n=1 Participants
Participants received LUM001 tablet orally once daily at a dose of 1 mg during Week 2 of the treatment period.
|
Maralixibat (LUM001) 2.5 mg
n=2 Participants
Participants received LUM001 tablet orally once daily at a dose of 2.5 mg during Week 3 of the treatment period.
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Maralixibat (LUM001) 5 mg
n=2 Participants
Participants received LUM001 tablet orally once daily at a dose of 5 mg during Week 4 of the treatment period.
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Maralixibat (LUM001) 7.5 mg
n=1 Participants
Participants received LUM001 tablet orally once daily at a dose of 7.5 mg during Week 5 of the treatment period.
|
Maralixibat (LUM001) 10 mg
n=21 Participants
Participants received LUM001 tablet orally once daily at a dose of 10 mg during Week 6 of the treatment period followed by stable dosing of 10 mg for 8 weeks.
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|---|---|---|---|---|---|
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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1 participant
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2 participant
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2 participant
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1 participant
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19 participant
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PRIMARY outcome
Timeframe: Baseline, Week 14Population: Modified intent-to-treat (mITT) population included all participants who received at least 1 dose of investigational product and had at least 1 post baseline serum bile acid laboratory assessment.
Serum bile acid levels were evaluated using blood samples collected.
Outcome measures
| Measure |
Maralixibat (LUM001) 1 mg
n=27 Participants
Participants received LUM001 tablet orally once daily at a dose of 1 mg during Week 2 of the treatment period.
|
Maralixibat (LUM001) 2.5 mg
Participants received LUM001 tablet orally once daily at a dose of 2.5 mg during Week 3 of the treatment period.
|
Maralixibat (LUM001) 5 mg
Participants received LUM001 tablet orally once daily at a dose of 5 mg during Week 4 of the treatment period.
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Maralixibat (LUM001) 7.5 mg
Participants received LUM001 tablet orally once daily at a dose of 7.5 mg during Week 5 of the treatment period.
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Maralixibat (LUM001) 10 mg
Participants received LUM001 tablet orally once daily at a dose of 10 mg during Week 6 of the treatment period followed by stable dosing of 10 mg for 8 weeks.
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|---|---|---|---|---|---|
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Change From Baseline in Fasting Serum Bile Acid Level at Week 14
Baseline
|
38.941 micromoles per liter
Standard Deviation 38.6614
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—
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—
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—
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—
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Change From Baseline in Fasting Serum Bile Acid Level at Week 14
Change From Baseline
|
-14.841 micromoles per liter
Standard Deviation 31.3709
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Baseline, Week 14Population: mITT population included all participants who received at least 1 dose of investigational product and had at least 1 post baseline serum bile acid laboratory assessment.
Levels of liver enzymes such as Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) in serum were evaluated.
Outcome measures
| Measure |
Maralixibat (LUM001) 1 mg
n=27 Participants
Participants received LUM001 tablet orally once daily at a dose of 1 mg during Week 2 of the treatment period.
|
Maralixibat (LUM001) 2.5 mg
Participants received LUM001 tablet orally once daily at a dose of 2.5 mg during Week 3 of the treatment period.
|
Maralixibat (LUM001) 5 mg
Participants received LUM001 tablet orally once daily at a dose of 5 mg during Week 4 of the treatment period.
|
Maralixibat (LUM001) 7.5 mg
Participants received LUM001 tablet orally once daily at a dose of 7.5 mg during Week 5 of the treatment period.
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Maralixibat (LUM001) 10 mg
Participants received LUM001 tablet orally once daily at a dose of 10 mg during Week 6 of the treatment period followed by stable dosing of 10 mg for 8 weeks.
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|---|---|---|---|---|---|
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Change From Baseline in Liver Enzyme Levels in Serum
ALP: Baseline
|
471.6 units per liter (U/L)
Standard Deviation 316.93
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—
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—
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—
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—
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Change From Baseline in Liver Enzyme Levels in Serum
ALT: Baseline
|
108.5 units per liter (U/L)
Standard Deviation 78.95
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—
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—
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—
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—
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Change From Baseline in Liver Enzyme Levels in Serum
ALT: Change From Baseline
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10.5 units per liter (U/L)
Standard Deviation 63.07
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—
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—
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—
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—
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Change From Baseline in Liver Enzyme Levels in Serum
AST: Baseline
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88.3 units per liter (U/L)
Standard Deviation 43.70
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—
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—
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—
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—
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Change From Baseline in Liver Enzyme Levels in Serum
AST: Change From Baseline
|
11.7 units per liter (U/L)
Standard Deviation 34.14
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—
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—
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—
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—
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Change From Baseline in Liver Enzyme Levels in Serum
ALP: Change From Baseline
|
36.7 units per liter (U/L)
Standard Deviation 170.87
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Baseline, Week 14Population: mITT population included all participants who received at least 1 dose of investigational product and had at least 1 post baseline serum bile acid laboratory assessment.
Total Bilirubin and Direct (Conjugated) Bilirubin levels were evaluated.
Outcome measures
| Measure |
Maralixibat (LUM001) 1 mg
n=27 Participants
Participants received LUM001 tablet orally once daily at a dose of 1 mg during Week 2 of the treatment period.
|
Maralixibat (LUM001) 2.5 mg
Participants received LUM001 tablet orally once daily at a dose of 2.5 mg during Week 3 of the treatment period.
|
Maralixibat (LUM001) 5 mg
Participants received LUM001 tablet orally once daily at a dose of 5 mg during Week 4 of the treatment period.
|
Maralixibat (LUM001) 7.5 mg
Participants received LUM001 tablet orally once daily at a dose of 7.5 mg during Week 5 of the treatment period.
|
Maralixibat (LUM001) 10 mg
Participants received LUM001 tablet orally once daily at a dose of 10 mg during Week 6 of the treatment period followed by stable dosing of 10 mg for 8 weeks.
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|---|---|---|---|---|---|
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Change From Baseline in Bilirubin Levels at Week 14
Total Bilirubin Level: Baseline
|
1.22 milligram per deciliter (mg/dL)
Standard Deviation 0.775
|
—
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—
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—
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—
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Change From Baseline in Bilirubin Levels at Week 14
Total Bilirubin Level: Change From Baseline
|
0.24 milligram per deciliter (mg/dL)
Standard Deviation 0.666
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—
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—
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—
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—
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Change From Baseline in Bilirubin Levels at Week 14
Conjugated Bilirubin Level: Baseline
|
0.60 milligram per deciliter (mg/dL)
Standard Deviation 0.510
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—
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—
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—
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—
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Change From Baseline in Bilirubin Levels at Week 14
Conjugated Bilirubin Level: Change From Baseline
|
0.19 milligram per deciliter (mg/dL)
Standard Deviation 0.450
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Baseline, Week 14Population: mITT population included all participants who received at least 1 dose of investigational product and had at least 1 post baseline serum bile acid laboratory assessment.
The Adult ItchRO instrument was completed twice daily using an electronic diary (eDiary). Each morning and evening score had a range from 0-10, with the higher score indicating increasing itch severity. The following was used for assessing the Adult ItchRO daily score: The score which represented the most severe itching for the day (morning or evening) was taken for each day as the daily score (maximum daily score of 10); If only 1 of the 2 scores was available for the day, the score that was available was used as the daily score; If both the morning and the evening scores were missing, the score was considered missing for the day.
Outcome measures
| Measure |
Maralixibat (LUM001) 1 mg
n=27 Participants
Participants received LUM001 tablet orally once daily at a dose of 1 mg during Week 2 of the treatment period.
|
Maralixibat (LUM001) 2.5 mg
Participants received LUM001 tablet orally once daily at a dose of 2.5 mg during Week 3 of the treatment period.
|
Maralixibat (LUM001) 5 mg
Participants received LUM001 tablet orally once daily at a dose of 5 mg during Week 4 of the treatment period.
|
Maralixibat (LUM001) 7.5 mg
Participants received LUM001 tablet orally once daily at a dose of 7.5 mg during Week 5 of the treatment period.
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Maralixibat (LUM001) 10 mg
Participants received LUM001 tablet orally once daily at a dose of 10 mg during Week 6 of the treatment period followed by stable dosing of 10 mg for 8 weeks.
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|---|---|---|---|---|---|
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Change From Baseline in Pruritus as Measured by Adult Itch Reported Outcome (ItchRO) Weekly Sum Score
Baseline
|
15.00 units on scale
Standard Deviation 18.735
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—
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—
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—
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—
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Change From Baseline in Pruritus as Measured by Adult Itch Reported Outcome (ItchRO) Weekly Sum Score
Change From Baseline
|
-7.67 units on scale
Standard Deviation 16.326
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—
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—
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—
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—
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OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 14Population: mITT population included all participants who received at least 1 dose of investigational product and had at least 1 post baseline serum bile acid laboratory assessment.
Total cholesterol (TC) level and low density lipoprotein cholesterol (LDLC) level were considered as biochemical markers of cholestasis.
Outcome measures
| Measure |
Maralixibat (LUM001) 1 mg
n=27 Participants
Participants received LUM001 tablet orally once daily at a dose of 1 mg during Week 2 of the treatment period.
|
Maralixibat (LUM001) 2.5 mg
Participants received LUM001 tablet orally once daily at a dose of 2.5 mg during Week 3 of the treatment period.
|
Maralixibat (LUM001) 5 mg
Participants received LUM001 tablet orally once daily at a dose of 5 mg during Week 4 of the treatment period.
|
Maralixibat (LUM001) 7.5 mg
Participants received LUM001 tablet orally once daily at a dose of 7.5 mg during Week 5 of the treatment period.
|
Maralixibat (LUM001) 10 mg
Participants received LUM001 tablet orally once daily at a dose of 10 mg during Week 6 of the treatment period followed by stable dosing of 10 mg for 8 weeks.
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|---|---|---|---|---|---|
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Change From Baseline for Other Biochemical Markers of Cholestasis: Total Cholesterol, Low Density Lipoprotein Cholesterol
TC Level: Baseline
|
213.0 mg/dL
Standard Deviation 50.62
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—
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—
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—
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—
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Change From Baseline for Other Biochemical Markers of Cholestasis: Total Cholesterol, Low Density Lipoprotein Cholesterol
TC Level: Change From Baseline
|
-21.2 mg/dL
Standard Deviation 25.46
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—
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—
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—
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—
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Change From Baseline for Other Biochemical Markers of Cholestasis: Total Cholesterol, Low Density Lipoprotein Cholesterol
LDLC Level: Baseline
|
121.4 mg/dL
Standard Deviation 40.52
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—
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—
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—
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—
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Change From Baseline for Other Biochemical Markers of Cholestasis: Total Cholesterol, Low Density Lipoprotein Cholesterol
LDLC Level: Change From Baseline
|
-16.3 mg/dL
Standard Deviation 17.64
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—
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—
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—
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—
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Adverse Events
Maralixibat (LUM001)
Serious adverse events
| Measure |
Maralixibat (LUM001)
n=27 participants at risk
Participants received LUM001 tablet orally once daily at a dose of 0.5 milligram (mg) during Week 1; 1 mg during Week 2; 2.5 mg during Week 3; 5 mg during Week 4; 7.5 mg during Week 5; 10 mg during Week 6 followed by stable dosing of 10 mg for 8 weeks.
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|---|---|
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Gastrointestinal disorders
Melaena
|
3.7%
1/27 • Number of events 1 • From start of study drug administration up to follow up (Week 18)
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Gastrointestinal disorders
Upper gastrointestinal haemorrhage
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3.7%
1/27 • Number of events 1 • From start of study drug administration up to follow up (Week 18)
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|
Infections and infestations
Appendicitis
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3.7%
1/27 • Number of events 1 • From start of study drug administration up to follow up (Week 18)
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Injury, poisoning and procedural complications
Joint dislocation
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3.7%
1/27 • Number of events 1 • From start of study drug administration up to follow up (Week 18)
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Hepatobiliary disorders
Cholangitis
|
3.7%
1/27 • Number of events 1 • From start of study drug administration up to follow up (Week 18)
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Other adverse events
| Measure |
Maralixibat (LUM001)
n=27 participants at risk
Participants received LUM001 tablet orally once daily at a dose of 0.5 milligram (mg) during Week 1; 1 mg during Week 2; 2.5 mg during Week 3; 5 mg during Week 4; 7.5 mg during Week 5; 10 mg during Week 6 followed by stable dosing of 10 mg for 8 weeks.
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|---|---|
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Musculoskeletal and connective tissue disorders
Arthralgia
|
11.1%
3/27 • Number of events 9 • From start of study drug administration up to follow up (Week 18)
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Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.4%
2/27 • Number of events 2 • From start of study drug administration up to follow up (Week 18)
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Musculoskeletal and connective tissue disorders
Neck pain
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7.4%
2/27 • Number of events 2 • From start of study drug administration up to follow up (Week 18)
|
|
Gastrointestinal disorders
Abdominal discomfort
|
11.1%
3/27 • Number of events 4 • From start of study drug administration up to follow up (Week 18)
|
|
Gastrointestinal disorders
Abdominal distension
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14.8%
4/27 • Number of events 5 • From start of study drug administration up to follow up (Week 18)
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Gastrointestinal disorders
Abdominal pain
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29.6%
8/27 • Number of events 8 • From start of study drug administration up to follow up (Week 18)
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Gastrointestinal disorders
Abdominal pain upper
|
7.4%
2/27 • Number of events 4 • From start of study drug administration up to follow up (Week 18)
|
|
Gastrointestinal disorders
Diarrhoea
|
51.9%
14/27 • Number of events 27 • From start of study drug administration up to follow up (Week 18)
|
|
Gastrointestinal disorders
Frequent bowel movements
|
7.4%
2/27 • Number of events 2 • From start of study drug administration up to follow up (Week 18)
|
|
Gastrointestinal disorders
Nausea
|
33.3%
9/27 • Number of events 12 • From start of study drug administration up to follow up (Week 18)
|
|
General disorders
Asthenia
|
7.4%
2/27 • Number of events 2 • From start of study drug administration up to follow up (Week 18)
|
|
General disorders
Fatigue
|
14.8%
4/27 • Number of events 4 • From start of study drug administration up to follow up (Week 18)
|
|
General disorders
Pyrexia
|
7.4%
2/27 • Number of events 2 • From start of study drug administration up to follow up (Week 18)
|
|
Infections and infestations
Nasopharyngitis
|
7.4%
2/27 • Number of events 2 • From start of study drug administration up to follow up (Week 18)
|
|
Hepatobiliary disorders
Cholangitis
|
7.4%
2/27 • Number of events 2 • From start of study drug administration up to follow up (Week 18)
|
|
Hepatobiliary disorders
Hepatomegaly
|
7.4%
2/27 • Number of events 2 • From start of study drug administration up to follow up (Week 18)
|
|
Nervous system disorders
Headache
|
22.2%
6/27 • Number of events 7 • From start of study drug administration up to follow up (Week 18)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER