An Extension Study to Evaluate the Long-Term Safety and Durability of Effect of LUM001 in the Treatment of Cholestatic Liver Disease in Pediatric Participants With Alagille Syndrome (IMAGINE-II)
|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: NCT02117713|
Recruitment Status : Active, not recruiting
First Posted : April 21, 2014
Last Update Posted : June 28, 2018
|Condition or disease||Intervention/treatment||Phase|
|Alagille Syndrome||Drug: LUM001||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter Extension Study to Evaluate the Long-Term Safety and Durability of the Therapeutic Effect of LUM001, an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi), in the Treatment of Cholestatic Liver Disease in Pediatric Subjects With Alagille Syndrome|
|Actual Study Start Date :||March 16, 2015|
|Estimated Primary Completion Date :||June 28, 2019|
|Estimated Study Completion Date :||June 28, 2019|
Participant will receive LUM001 as oral solution once daily based on participant's weight. The dose will be escalated from 14, 35, 70, 140 and 280 microgram per kilogram per day (mcg/kg/day) for 4-week dose escalation period. During 8-weeks of dose optimization period, drug will be adjusted in titrated manner and will continue dosing to complete the stable dosing and safety monitoring periods for up to 96 weeks of cumulative LUM001 exposure in this study. Long-term optional follow-up treatment period will be maintained at the same week 96 dose level for participants roll over into this treatment period.
LUM001 will be administered as oral solution once daily based on participant's weight in dose adjustment manner. The dose will be escalated from 14, 35, 70, 140 and 280 mcg/kg/day for 4-week dose escalation period. During 8-weeks of dose optimization period, drug will be adjusted in titrated manner and will continue dosing to complete the stable dosing and safety monitoring periods for up to 96 weeks of cumulative LUM001 exposure in this study. Long-term optional follow-up treatment period will be maintained at the same week 96 dose level for participants roll over into this treatment period.
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Baseline to Week 144 ]An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product.
- Change From Baseline in the Fasting Serum Bile Acid Levels Associated with ALGS [ Time Frame: Baseline, Week 48 ]Mean change in the serum bile acid level will be measured overall from baseline (Day 0) of LUM001-301 and baseline (Day 0) of LUM001-305.
- Change From Baseline in the Pruritus Associated with ALGS [ Time Frame: Baseline, End of treatment (EOT)/Week 144 ]Mean change in the pruritus will be measured by the electronic diary Itch Reported Outcome Instrument (ItchRO), (ItchRO(Obs)TM, caregiver instrument/ItchRO(Pt) TM patient instrument).
- Change From Baseline in the Biochemical Markers of Cholestasis and Liver Disease [ Time Frame: Baseline, EOT/Week 144 ]Mean change in biochemical markers of cholestasis and liver disease for example alanine aminotransferase [ALT], alkaline phosphate [ALP], gamma-glutamyltransferase [GGT] and bilirubin [total and direct]) from baseline (Day 0) of LUM001-301 and baseline (Day 0) of LUM001-305 will be measured.
- Change From Baseline in the Xanthomas as Measured by Clinician Xanthoma Scale Associated with ALGS [ Time Frame: Baseline, EOT/Week 144 ]The clinician's assessment of the participant's xanthomatosis is focused on the number of lesions present and the degree to which the participant's lesions interfere or limit his or her activities. The clinician xanthoma scale uses a 5-point scale, in which 0 represents no evidence of xanthomatosis, 1 represents fewer than 20 scattered individual lesions, 2 represents more than 20 lesions that do not interfere with or limit activities, 3 represents large numbers of lesions that by their large numbers or size cause distortion of the face or extremities, and 4 represents xanthomas that interfere with function (such as hand use or ability to walk) because of excess size or number.
- Expanded Dosing Range [ Time Frame: From start of study drug administration up to EOT/148 weeks ]Dosing range to identify doses necessary to achieve the optimal benefit-to-risk ration for this participant population will be assessed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02117713
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027|
|University of California at San Francisco Children's Hospital|
|San Francisco, California, United States, 94143|
|United States, Colorado|
|Children's Hospital Colorado|
|Aurora, Colorado, United States, 80045|
|United States, Georgia|
|Children's Healthcare of Atlanta|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|Ann & Robert H. Lurie Children's Hospital of Chicago|
|Chicago, Illinois, United States, 60611|
|United States, Indiana|
|Riley Hospital for Children|
|Indianapolis, Indiana, United States, 46202|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|United States, Pennsylvania|
|The Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19147|
|Children's Hospital of Pittsburgh of UPMC|
|Pittsburgh, Pennsylvania, United States, 15224|
|United States, Texas|
|Baylor College of Medicine/Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|United States, Utah|
|University of Utah|
|Salt Lake City, Utah, United States, 84113|
|United States, Washington|
|Seattle Children's Hospital|
|Seattle, Washington, United States, 98105|
|The Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G 1X8|
|Study Director:||Shire Physician||Shire|