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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:
Collaborator:
Lumena Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT02057718
First received: February 5, 2014
Last updated: November 22, 2016
Last verified: November 2016
  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 the biochemical markers and pruritus associated with PFIC.

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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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:
  • Evaluate the long-term safety and tolerability of LUM001 in pediatric subjects with PFIC measured by the pharmacodynamic effect on serum bile acid levels. [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]
    Exposure to study drug will be measured approximately 2-4 hours post dose and data will be summarized and listed across the treatment period by treatment group.

  • Evaluate the effect of LUM001 by the mean change from baseline to Week 13 in fasting serum bile acid level [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
  • Evaluate the effect of LUM001 by the mean change from baseline to Week 13 on biochemical markers of cholestasis and liver disease [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
    Alanine aminotransferase (ALT) and bilirubin (total and direct).

  • Evaluate the effect of LUM001 by the mean change from baseline to Week 13 on pruritus in pediatric subjects with PFIC as measured by Itch Reported Outcome (ItchRO). [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Evaluate Safety and Tolerability of LUM001 through 72 weeks and qualifed subjects who contintue through Week 124 [ Time Frame: Up to 124 weeks ] [ Designated as safety issue: Yes ]
    Safety and clinical laboratory evaluations and a physical exam (including collection of vital signs, height and weight measurements) will be completed at each clinic visit.


Estimated Enrollment: 24
Study Start Date: March 2014
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LUM001
LUM001 administered orally once each day
Drug: LUM001
LUM001 oral dose

  Eligibility

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

Inclusion Criteria:

  1. Male or female subjects 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 >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
  3. GGTP <100 IU/L at screening.
  4. Females of childbearing potential must have a negative urine or serum pregnancy test [β human chorionic gonadotropin (β-hCG)] during screening and a negative urine pregnancy test at the Baseline (Day 0) visit.
  5. Sexually active females must be prepared to use an effective method (≤ 1% failure rate) of 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. Subjects expected to have a consistent caregiver(s) for the duration of the first 13 weeks of the study.
  10. Caregivers (and age appropriate subjects) must be willing and able to use an eDiary device as required by the study.
  11. Caregivers (and age appropriate subjects) using the eDiary must digitally accept the licensing agreement in the eDiary software at the outset of the study.
  12. Caregivers (and age appropriate subjects) 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).

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. Subjects 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 g/L, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy].
  5. ALT > 15 x 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 half-lives 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 subject, or interfere with the subject participating in or completing the study.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
Lumena Pharmaceuticals, Inc.
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 
Study First Received: February 5, 2014
Last Updated: November 22, 2016
Health Authority: Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Canada: Health Canada

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

ClinicalTrials.gov processed this record on December 09, 2016