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Trial record 5 of 13 for:    Alagille Syndrome

An Extension Study to Evaluate the Long-Term Safety and Durability of Effect of LUM001 in the Treatment of Cholestatic Liver Disease in Pediatric Subjects With Alagille Syndrome (IMAGINE-II)

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ClinicalTrials.gov Identifier: NCT02117713
Recruitment Status : Active, not recruiting
First Posted : April 21, 2014
Last Update Posted : August 7, 2018
Sponsor:
Collaborators:
Lumena Pharmaceuticals, Inc.
Childhood Liver Disease Research and Education Network
Information provided by (Responsible Party):
Shire

Brief Summary:
This is a multicentre, extension study of LUM001 in children diagnosed with Alagille Syndrome who have completed participation in a core LUM001 treatment protocol. The primary objective is to evaluate long-term safety and tolerability of LUM001. Efficacy will be assessed by evaluating the effect of LUM001 on the biochemical markers and pruritus associated with Alagille Syndrome.

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: Double (Participant, Investigator)
Primary Purpose: Treatment
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 : October 19, 2018
Estimated Study Completion Date : October 19, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Diseases

Arm Intervention/treatment
Experimental: LUM001
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. Dosing during, long-term optional follow-up treatment periods 1 and 2 will be maintained at the same dose levels as at weeks 96 and 144 for participants rolling over into these treatment periods respectively.
Drug: LUM001
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. Dosing during, long-term optional follow-up treatment periods 1 and 2 will be maintained at the same dose levels as at weeks 96 and 144 for participants rolling over into these treatment periods respectively.




Primary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Baseline to Week 216 ]
    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.


Secondary Outcome Measures :
  1. Change From Baseline in the Pruritus Associated with ALGS [ Time Frame: Baseline, End of treatment (EOT)/Week 216 ]
    Mean change in pruritus will be measured from baseline by the electronic diary Itch Reported Outcome Instrument (ItchRO), (ItchRO(Obs)™, caregiver instrument/ItchRO(Pt)™ patient instrument).

  2. 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.

  3. Change From Baseline in the Biochemical Markers of Cholestasis and Liver Disease [ Time Frame: Baseline, EOT/Week 216 ]
    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.

  4. Change From Baseline in the Xanthomas as Measured by Clinician Xanthoma Scale Associated with ALGS [ Time Frame: Baseline, EOT/Week 216 ]
    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.

  5. Expanded Dosing Range [ Time Frame: From start of study drug administration up to EOT/216 weeks ]
    Dosing range to identify doses necessary to achieve the optimal benefit-to-risk ration for this participant population will be assessed.



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Ages Eligible for Study:   1 Year to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, 12 months to 18 years of age.
  2. Competent to provide informed consent and assent (per institutional review board/Ethics Committee [IRB/EC]), as appropriate.
  3. Completed participation in the LUM001-301 protocol.
  4. Females of childbearing potential must have a negative urine pregnancy test [beta human chorionic gonadotropin (beta-hCG)] at the Baseline Visit.
  5. Sexually active females must be prepared to use an effective method of contraception during the trial.

    Effective methods of contraception are considered to be:

    1. Hormonal (for example, contraceptive pill, patch, intramuscular implant or injection); or
    2. Barrier method, for exampe, (a) condom with spermicide, or (b) diaphragm, with spermicide; or
    3. Intrauterine device (IUD).
  6. Participants above the age of assent and caregivers and children must be able to read and understand English or Spanish.
  7. Caregivers (and age appropriate participants) must have access to phone for scheduled calls from study site.
  8. Caregivers (and age appropriate participants) must be willing and able to complete a daily electronic diary (ItchRO) during the first consecutive 12 weeks of the study and then for 4 consecutive weeks following the Week 24 and Week 44 visits.
  9. Caregivers (and age appropriate participants) must digitally accept the licensing agreement in the ItchRO electronic diary software at the outset of the study.
  10. Eligible participants must be able to adhere to local Ethics Committee or Institutional Review Board (IRB) blood volume limits for laboratory testing.
  11. The participant has completed the protocol either through Week 144, or the End of Trial visit, or has received permission from the sponsor and the Premier Medical monitor to re-enter the study in the long-term, optional follow-up treatment period 2.
  12. Females of child-bearing potential must have a negative urine or serum pregnancy test (beta-HCG]) at the time of entry into the long-term optional follow-up treatment period 2.
  13. Male and female participants of child-bearing potential who are sexually active, or are not currently sexually active, but become sexually active during the study or for 30 days following the last dose of study drug, must agree to use acceptable contraception during the study.
  14. Informed consent and assent (per IRB/EC) as appropriate.
  15. Caregivers (and age appropriate participants) must have access to phone for scheduled calls from study site.
  16. Caregivers (and age appropriate participants) must be willing to follow the rules of eDiary completion.

Exclusion Criteria:

  1. Experienced an adverse event or serious adverse event (SAE) related to the study drug during the LUM001-301 protocol that led to the discontinuation of the participant from the core study.
  2. Any conditions or abnormalities (including laboratory abnormalities) which in the opinion of the Investigator, Medical Monitor or ChiLDReN Protocol Chair, may compromise the safety of the participant, or interfere with the participant participating in or completing the study.
  3. History or known presence of gallstones or kidney stones.
  4. History of non-adherence during the participant's participation in the LUM001-301 protocol. Non-adherence is defined by dosing compliance (dosing compliance is calculated by [the total number of doses that were actually taken by the participant] divided by [the total number of doses that should have been taken by the participant] multiplied by 100) of less than 80% in the LUM001-301 protocol.
  5. Unlikely to comply with the study protocol, or unsuitable for any other reason, as judged by the investigator.
  6. All above exclusion criteria will apply upon re-entry into the long-term, optional follow-up treatment period 2.

Information from the National Library of Medicine

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


Locations
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
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
Shire
Lumena Pharmaceuticals, Inc.
Childhood Liver Disease Research and Education Network
Investigators
Study Director: Shire Director Shire

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02117713     History of Changes
Other Study ID Numbers: LUM001-305
SHP625-305 ( Other Identifier: Shire )
First Posted: April 21, 2014    Key Record Dates
Last Update Posted: August 7, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Syndrome
Alagille Syndrome
Liver Diseases
Cholestasis
Disease
Pathologic Processes
Digestive System Diseases
Cholestasis, Intrahepatic
Bile Duct Diseases
Biliary Tract Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn