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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

April 16, 2014
April 21, 2014
August 7, 2018
March 16, 2015
October 19, 2018   (Final data collection date for primary outcome measure)
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.
Safety and tolerability [ Time Frame: 48 weeks ]
Adverse events, changes in vital signs, laboratory and other safety parameters from baseline to week 48
Complete list of historical versions of study NCT02117713 on ClinicalTrials.gov Archive Site
  • 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).
  • 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 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.
  • 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.
  • 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.
Efficacy [ Time Frame: 48 weeks ]
Changes in serum bile acids, pruritus, and other biochemical markers of cholestasis and liver disease from baseline to week 48
Not Provided
Not Provided
 
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
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
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.
Not Provided
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Alagille Syndrome
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.
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.
Intervention: Drug: LUM001
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
36
24
October 19, 2018
October 19, 2018   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
1 Year to 18 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   United States
 
 
NCT02117713
LUM001-305
SHP625-305 ( Other Identifier: Shire )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Shire
Shire
  • Lumena Pharmaceuticals, Inc.
  • Childhood Liver Disease Research and Education Network
Study Director: Shire Director Shire
Shire
August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP