Clinical Trial Results:
A Pilot, Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of LUM001, an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTi), in Patients with Primary Sclerosing Cholangitis (PSC)
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Summary
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EudraCT number |
2014-005558-21 |
Trial protocol |
GB |
Global end of trial date |
12 Feb 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Jan 2017
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First version publication date |
07 Jan 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
LUM001-401
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02061540 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Lumena Pharmaceutical LLC
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Sponsor organisation address |
300 Shire Way, Lexington, MA, United States, 02421
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Public contact |
Study Physician, Shire, 1 866-842-5335,
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Scientific contact |
Study Physician, Shire, 1 866-842-5335,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Feb 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Feb 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the safety and tolerability of LUM001 in subjects with Primary Sclerosing Cholangitis (PSC) during 14 weeks of treatment.
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Protection of trial subjects |
This study was conducted in accordance with International Conference on Harmonization of Good Clinical Practice, with exceptions that have been addressed, as well as all applicable federal, local ethical and legal requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Apr 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 14
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Country: Number of subjects enrolled |
Canada: 9
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Country: Number of subjects enrolled |
United Kingdom: 4
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Worldwide total number of subjects |
27
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EEA total number of subjects |
4
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
25
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted in 8 centers in Great Britain, Canada, and the United States between 22 April 2014 (first subject first visit) and 12 February 2016 (last subject last visit). | ||||||||||||
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Pre-assignment
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Screening details |
A total of 37 subjects were screened, of them 27 subjects were enrolled in the study. 5 subjects were down-titrated during the study. | ||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Maralixibat (LUM001) | ||||||||||||
Arm description |
Subjects 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. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Maralixibat chloride
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Investigational medicinal product code |
LUM001
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received LUM001 tablet orally at a dose of 0.5 milligram (mg); 1 mg; 2.5 mg; 5 mg; 7.5 mg; 10 mg.
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Baseline characteristics reporting groups
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Reporting group title |
Maralixibat (LUM001)
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Reporting group description |
Subjects 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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End points reporting groups
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Reporting group title |
Maralixibat (LUM001)
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Reporting group description |
Subjects 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. | ||
Subject analysis set title |
Maralixibat (LUM001) 1 mg
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Subjects received LUM001 tablet orally once daily at a dose of 1 mg during Week 2 of the treatment period.
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Subject analysis set title |
Maralixibat (LUM001) 2.5 mg
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Subjects received LUM001 tablet orally once daily at a dose of 2.5 mg during Week 3 of the treatment period.
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Subject analysis set title |
Maralixibat (LUM001) 5 mg
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Subjects received LUM001 tablet orally once daily at a dose of 5 mg during Week 4 of the treatment period.
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Subject analysis set title |
Maralixibat (LUM001) 7.5 mg
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Subjects received LUM001 tablet orally once daily at a dose of 7.5 mg during Week 5 of the treatment period.
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Subject analysis set title |
Maralixibat (LUM001) 10 mg
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Subjects 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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End point title |
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) [1] | |||||||||||||||||||||
End point description |
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. Safety population included all subjects who received at least 1 dose of the investigational product was analysed for this end point.
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End point type |
Primary
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End point timeframe |
From start of study drug administration until Week 18
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Inferential statistical analysis was not performed since descriptive statistical analysis was planned for this endpoint. |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change From Baseline in Fasting Serum Bile Acid Level at Week 14 [2] | ||||||||||||
End point description |
Serum bile acid levels were evaluated using blood samples collected. Modified intent-to-treat (mITT) population included all subjects who received at least 1 dose of investigational product and had at least 1 post baseline serum bile acid laboratory assessment was analysed for this end point.
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End point type |
Primary
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End point timeframe |
Baseline, Week 14
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: EudraCT database does not allow to report only one treatment group in statistical analyses section. Due to this format constraint, we are not able to present within the group inferential statistical analysis of single arm. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Liver Enzyme Levels in Serum at Week 14 | ||||||||||||||||||||
End point description |
Levels of liver enzymes such as Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) in serum were evaluated. mITT population was analysed for this end point.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 14
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Change From Baseline in Bilirubin Levels at Week 14 | ||||||||||||||||
End point description |
Total Bilirubin and Direct (Conjugated) Bilirubin levels were evaluated. mITT population was analysed for this end point.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 14
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in Pruritus as Measured by Adult Itch Reported Outcome (ItchRO) Weekly Sum Score at Week 14 | ||||||||||||
End point description |
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. mITT population was analysed for this end point.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 14
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline for Other Biochemical Markers of Cholestasis at Week 14: Total Cholesterol, Low Density Lipoprotein Cholesterol | ||||||||||||||||
End point description |
Total cholesterol (TC) level and low density lipoprotein cholesterol (LDLC) level were considered as biochemical markers of cholestasis. mITT population was analysed for this end point.
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End point type |
Other pre-specified
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End point timeframe |
Baseline, Week 14
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From start of study drug administration up to follow up (Week 18)
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Maralixibat (LUM001)
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Reporting group description |
Subjects 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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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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09 Dec 2014 |
- Removed the Mayo risk score from Inclusion Criterion
- Added a qualification for inclusion for subjects receiving azathioprine.
- Exclusion Criterion removed the restriction for azathioprine |
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10 Feb 2015 |
- Added a Data Monitoring Board for review of serious adverse events (SAEs) and other key safety data.
- Provided for dosing halts for instances of 3 or more subjects exhibiting drug-related toxicity of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or greater in the same system organ class (SOC)
- Clarified stopping rules for liver chemistry elevations
- Safety monitoring guidelines were added for triglycerides elevations relative to investigational product dosing
- Clarified stopping rules for suspending investigational product dosing until DMB investigations if 5 subjects discontinue dosing outside the serum biochemistry parameters specified.
- A statement requiring study investigators to discuss with the medical monitor removing subjects prior to their withdrawal from a study was deleted. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
