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Open Label Study to Evaluate Efficacy and Long Term Safety of LUM001 in the Treatment of Cholestatic Liver Disease in Patients With Progressive Familial Intrahepatic Cholestasis (INDIGO)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02057718
First Posted: February 7, 2014
Last Update Posted: September 4, 2017
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.
Information provided by (Responsible Party):
Shire
  Purpose
This is an open label study in children with Progressive Familial Intrahepatic Cholestasis (PFIC) designed to evaluate the safety and efficacy of LUM001. Efficacy will be assessed by evaluating the effect of LUM001 on pruritus and the biochemical markers of pruritus associated with PFIC.

Condition Intervention Phase
Progressive Familial Intrahepatic Cholestasis (PFIC) Drug: LUM001 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label Study of the Efficacy and Long Term Safety of LUM001, an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi), in the Treatment of Cholestatic Liver Disease in Pediatric Patients With Progressive Familial Intrahepatic Cholestasis

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • To evaluate the Safety and Tolerability of LUM001 in Pediatric Participants with Progressive Familial Intrahepatic Cholestasis (PFIC) [ Time Frame: From start of study treatment until Week 13 ]
    Safety and tolerability of LUM001 will be assessed for adverse events (AEs) and serious adverse events (SAEs), clinical laboratory results, vital signs, physical exam findings (including body weight and height), concomitant medication usage and serum alpha-fetoprotein (AFP). An AE is 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 is considered related to the investigational drug product.

  • To evaluate the effect of LUM001 on Serum Bile Acids in Pediatric Participants with Progressive Familial Intrahepatic Cholestasis (PFIC) [ Time Frame: From start of study treatment until Week 13 ]
    Change in serum bile acids from Baseline (Day 0) to Week 13 will be evaluated.

  • To evaluate the effect of LUM001 on Pruritus in Pediatric Participants with Progressive Familial Intrahepatic Cholestasis (PFIC) [ Time Frame: Baseline, Week 13 ]
    Pruritus will be assessed by using the Itch caregiver/patient reported outcome measure (ItchRO) administered as a twice daily electronic diary. The clinician's assessment of the participant's pruritus is focused on scratching and visible damage to the skin as a result of scratching as observed by the physician. The clinician scratch scale uses a 5-point scale, in which 0 designates no evidence of scratching and 4 designates cutaneous mutilation with bleeding, hemorrhage and scarring. It will be evaluated for change from Baseline (Day 0) to Week 13.

  • Effect of LUM001 on Biochemical Markers of Cholestasis and Liver Disease in Pediatric Participants with Progressive Familial Intrahepatic Cholestasis (PFIC) [ Time Frame: Baseline, Week 13 ]
    Biochemical markers of cholestasis and liver disease will include alanine aminotransferase (ALT), and bilirubin (total and direct).


Secondary Outcome Measures:
  • Evaluate the Long-term Safety and tolerability of LUM001 [ Time Frame: Baseline, Week 13 ]
    Safety and efficacy of LUM001 will be assessed for adverse events (AEs) and serious adverse events (SAEs), clinical laboratory results, vital signs, physical exam findings (including body weight and height), concomitant medication usage and serum alpha-fetoprotein (AFP).

  • Evaluate the long term efficacy of LUM001 in participants with Progressive Familial Intrahepatic Cholestasis (PFIC) [ Time Frame: Baseline, Week 13 ]
    Pruritus, biochemical markers of cholestasis and liver disease will be assessed at various time points throughout the study

  • Evaluate the effect of twice daily dosing and higher doses in Pediatric Participants with Progressive Familial Intrahepatic Cholestasis (PFIC) [ Time Frame: From Week 72 until the End of Treatment ]
    Higher doses and twice daily treatment will be explored in patients who have not had response to LUM001.

  • Evaluation of Level of Alpha-fetoprotein (AFP) [ Time Frame: From Week 72 until the End of Treatment ]
    Serum AFP as a clinical laboratory test will be measured for the screening of hepatocellular carcinoma.

  • Assessment of Palatability of the LUM001 Formulation [ Time Frame: From Week 72 until the End of ]
    A palatability questionnaire will be completed by the participants and/or caregiver (dependent on age) at each time points


Estimated Enrollment: 24
Actual Study Start Date: March 1, 2014
Estimated Study Completion Date: August 1, 2018
Estimated Primary Completion Date: August 1, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LUM001
Participants will receive LUM001 twice a day (BID).
Drug: LUM001
LUM001 oral dose up to twice a day (BID).

Detailed Description:
The study is divided into 5 parts: a 4-week dose escalation period, a 4-week stable dosing period, a 5-week stable dosing period, a 59-week long-term exposure period, and an optional follow-up treatment period for eligible participants who continue treatment with LUM001. Participants in the optional follow-up treatment period will continue to receive study drug until they are eligible to enter another LUM001 study or until LUM001 is available commercially, whichever occurs first.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female participants between the ages of 12 months and 18 years inclusive.
  2. Diagnosis of PFIC based on: (a) Intrahepatic cholestasis manifest by total serum bile acid greater than (>) 3x upper limit of normal for age; and, b or c: (b) Two documented mutant alleles in ATP8B1, or ABCB11; (c) Evidence of chronic liver disease meeting specific criteria.
  3. Gamma-glutamyl transpeptidase (GGTP) less than (<)100 IU/L at screening.
  4. Females of childbearing potential must have a negative urine or serum pregnancy test [βhuman chorionic gonadotropin (β-hCG)] during screening and a negative urine pregnancy test at the Baseline (Day 0) visit.
  5. Males and females of child-bearing potential who are sexually active, or are not currently sexually active during the study, but become sexually active during the period of the study and 30 days following the last dose of study drug, must agree and use acceptable contraception during the trial.
  6. Informed consent and assent (per IRB/EC) as appropriate.
  7. Access to phone for scheduled calls from study site.
  8. Caregivers and children above the age of assent must have the ability to read and understand one of the following languages: English, Spanish, US Spanish, French, German or Polish.
  9. Participants expected to have a consistent caregiver(s) for the duration of the first 13 weeks of the study.
  10. Caregivers (and age appropriate participants) must be willing and able to use an eDiary device as required by the study. To accommodate potential cultural restrictions within the FIC1 affected population a paper version of the ItchRO diary will be made available.
  11. Caregivers (and age appropriate participants) using the eDiary must digitally accept the licensing agreement in the eDiary software at the outset of the study.
  12. Caregivers (and age appropriate participants) must complete at least 10 eDiary reports (morning or evening) during each of two consecutive weeks of the screening period, prior to assignment (maximum possible reports = 14 per week). Participants using a paper diary must complete the same number of reports within the same timeframe.

Exclusion Criteria:

  1. Chronic diarrhea requiring specific intravenous fluid or nutritional intervention for the diarrhea and/or its sequelae.
  2. Surgical disruption of the enterohepatic circulation at the time at screening. Participants who have undergone reversal of a prior surgical procedure intended to disrupt enterohepatic circulation and who and have a permanently restored flow of bile acids from the liver to the terminal ileum may be eligible for the study upon consultation with the Sponsor Medical Monitor.
  3. Liver transplant.
  4. Decompensated cirrhosis [international normalized ratio (INR) > 1.5, albumin < 30 gram per liter (g/L), history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy].
  5. ALT >15×ULN at screening.
  6. History or presence of other liver disease.
  7. History or presence of any other disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs, including bile salt metabolism in the intestine (e.g., inflammatory bowel disease).
  8. Liver mass on imaging.
  9. Known diagnosis of human immunodeficiency virus (HIV) infection.
  10. Cancers except for in situ carcinoma, or cancers treated at least 5 years prior to screening with no evidence of recurrence.
  11. Any female who is pregnant or lactating or who is planning to become pregnant within 20 weeks of assignment.
  12. Any known history of alcohol or substance abuse.
  13. Administration of bile acid or lipid binding resins within 30 days prior to Baseline / Day 0 and throughout the trial.
  14. Administration of sodium phenylbutyrate within 30 days prior to Baseline / Day 0 and throughout the trial.
  15. Investigational drug, biologic, or medical device within 30 days prior to screening, or 5 halflives of the study agent, whichever is longer.
  16. History of non-adherence to medical regimens, unreliability, mental instability or incompetence that could compromise the validity of informed consent or lead to non-adherence with the study protocol based on Investigator judgment.
  17. Any other conditions or abnormalities which, in the opinion of the Investigator or Sponsor Medical Monitor, may compromise the safety of the participant, or interfere with the participant participating in or completing the study.
  Contacts and Locations
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): NCT02057718


Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
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, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
France
Hopital Femme Mere Enfant De Lyon
Bron, France, 69677
Poland
The Children's Memorial Health Institute
Warsaw, Poland, 04-730
United Kingdom
Birmingham Children's Hospital
Steelhouse Lane, Birmingham West Midlands, United Kingdom, B4 6NH
Leeds Teaching Hospital NHS Trust
Great George Street, Leeds, United Kingdom, LS1 3EX
Kings College Hospital
London, United Kingdom, SE5 9RS
Sponsors and Collaborators
Shire
Investigators
Study Director: Shire Physician Shire
  More Information

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02057718     History of Changes
Other Study ID Numbers: LUM001-501
2013-003833-14 ( EudraCT Number )
First Submitted: February 5, 2014
First Posted: February 7, 2014
Last Update Posted: September 4, 2017
Last Verified: August 2017
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

Keywords provided by Shire:
Bile duct diseases
Intrahepatic Cholestasis
Cholestasis
PFIC
Pruritus
Cholestatic Liver Disease

Additional relevant MeSH terms:
Liver Diseases
Cholestasis
Cholestasis, Intrahepatic
Digestive System Diseases
Bile Duct Diseases
Biliary Tract Diseases