Overview

This trial is active, not recruiting.

Condition progressive familial intrahepatic cholestasis (pfic)
Treatment lum001
Phase phase 2
Sponsor Shire
Collaborator Lumena Pharmaceuticals, Inc.
Start date March 2014
End date February 2018
Trial size 24 participants
Trial identifier NCT02057718, 2013-003833-14, LUM001-501

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
LUM001 administered orally once each day
lum001
LUM001 oral dose

Primary Outcomes

Measure
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
Evaluate the effect of LUM001 by the mean change from baseline to Week 13 in fasting serum bile acid level
time frame: 13 weeks
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
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

Eligibility Criteria

Male or female participants from 12 months up to 18 years old.

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.

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Shire.