The purpose of this study is to evaluate a drug (LUM001) that may help treat the liver and control itching in Alagille Syndrome. In this study, all children who are eligible to enrol will take study drug for 18 weeks, followed by a 4 week period where they will either take LUM001 or placebo. After this 4 week period, all patients will go back on active study drug treatment for the remaining 26 weeks.

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2013-005373-43-ES
• Date of registration: 22/05/2014
• Prospective Registration: Yes
• Primary sponsor: Lumena Pharmaceuticals Inc
• Public title: The purpose of this study is to evaluate a drug (LUM001) that may help treat the liver and control itching in Alagille Syndrome. In this study, all children who are eligible to enrol will take study drug for 18 weeks, followed by a 4 week period where they will either take LUM001 or placebo. After this 4 week period, all patients will go back on active study drug treatment for the remaining 26 weeks.
• Scientific title: Long-Term, Open-Label Study with a Double-Blind, Placebo Controlled, Randomized Drug Withdrawal Period of LUM001, an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi), in Patients with Alagille Syndrome - ICONIC
• Date of first enrolment: 05/08/2014
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005373-43
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: This trial also contains a double blind drug withdrawal period; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, France, Poland, Spain, United Kingdom

Contacts

• Name: Chief Operating Officer
• Affiliation: Lumena Pharmaceuticals Inc

• Name: Chief Operating Officer
• Affiliation: Lumena Pharmaceuticals Inc

Key inclusion & exclusion criteria

Inclusion criteria:
To participate in this study subjects must meet all of the following criteria:
1.Male or female between the ages of 12 months and 18 years inclusive.
2.Diagnosis of ALGS .
3.Evidence of cholestasis (one or more of the following):
a.Total serum bile acid > 3x ULN for age.
b.Conjugated bilirubin > 1 mg/dL.
c.Fat soluble vitamin deficiency otherwise unexplainable.
d.GGT > 3x ULN for age.
e.Intractable pruritus explainable only by liver disease.
4.Females of childbearing potential must have a negative serum pregnancy test during Screening.
5.Sexually active females must be prepared to use an effective method of contraception during the trial, such as:
a.Hormonal (e.g., contraceptive pill, patch, intramuscular implant or injection).
b.Barrier method, i.e., (a) condom (male or female) or (b) diaphragm, with spermicide.
c.Intrauterine device (IUD).
6.Subject is expected to have a consistent caregiver(s) for the duration of the study.
7.Informed consent and assent (per IRB/IEC) as appropriate.
8.Access to phone for scheduled calls from study site.
9.Caregivers (and age appropriate subjects) must be willing and able to use an eDiary device during the study.
10.Caregivers (and age appropriate subjects) must digitally accept the licensing agreement in the eDiary software.
11.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 (maximum possible reports = 14 per week).
12.Average daily score >2 on the Itch Reported Outcome (ItchRO?) questionnaire (maximum possible daily score of 4) for two consecutive weeks in the screening period, prior to dosing. A daily score is the higher of the scores for the morning and evening ItchRO. The average daily score is the sum of all daily scores divided by the number of days the ItchRO was completed.
Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects will be excluded from the study if they meet any of the following criteria:
1.Chronic diarrhea requiring ongoing intravenous fluid or nutritional intervention.
2.Surgical interruption of the enterohepatic circulation.
3.Previous liver transplant.
4.Decompensated cirrhosis [ALT >15 x ULN, INR >1.5 (unresponsive to vitamin K therapy), albumin < 3.0 gm/dL, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy].
5.History or presence of other concomitant liver disease.
6.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).
7.Known diagnosis of human immunodeficiency virus (HIV) infection.
8.Cancers except for in situ carcinoma, or cancers treated at least 5 years prior to Screening with no evidence of recurrence.
9.Recent medical history, or current status that suggests that the subject may be unable to complete the study.
10.Any female who is pregnant or lactating or who is planning to become pregnant during the study period.
11.Known history of alcohol or substance abuse.
12.Administration of bile acid or lipid binding resins within 28 days prior to screening and throughout the trial.
13.Receipt of investigational drug, biologic, or medical device within 28 days prior to Screening, or 5 half-lives of the study agent, whichever is longer.
14.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 upon Investigator judgment.
15.Any other conditions or abnormalities which, in the opinion of the Investigator or Medical Monitor, may compromise the safety of the subject, or interfere with the subject participating in or completing the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Alagille Syndrome
MedDRA version: 17.0 Level: PT Classification code 10053870 Term: Alagille syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Product Name: LUM001
Product Code: LUM001
Pharmaceutical Form: Powder and solvent for oral solution
INN or Proposed INN: LUM001
CAS Number: 228113-66-4
Current Sponsor code: LUM001
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 0.05-60
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Serum bile acid levels are measured at baseline, 12, 18, 22 and 48 weeks

Secondary Objective: Not applicable

Primary end point(s): The primary efficacy endpoint will be the mean change in serum bile acid levels from Week 18 to Week 22 for those who responded to LUM001 treatment, which is defined as subjects who had a >50% reduction in serum bile acid levels from baseline to Week 18.

Main Objective: The objectives of this study are:
?To evaluate the long-term safety and tolerability of LUM001 in children with ALGS.
?To evaluate the effect of LUM001 on serum bile acid levels in children with ALGS.
?To evaluate the effect of LUM001 on biochemical markers of cholestasis and liver disease in children with ALGS.
?To evaluate the effect of LUM001 on pruritus in children with ALGS.
?To evaluate the long-term durability of effect of LUM001 in children with ALGS during 48-weeks of treatment.

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy endpoints include mean change from Week 18 to Week 22 in liver enzymes (ALP, ALT, and bilirubin (total and direct)) and pruritus as measured by ItchRO (Observer ItchRO/patient ItchRO). Secondary efficacy endpoints also include mean change from baseline to Week 18 in serum bile acid level, liver enzymes (ALP, ALT, and bilirubin (total and direct)) and pruritus as measured by ItchRO (Observer ItchRO/Patient ItchRO)

Timepoint(s) of evaluation of this end point: These are measured throughout the trial by means of the subject eDiary and clinician scales and questionnaires.

Secondary ID(s)

LUM001-304

Source(s) of Monetary Support

Lumena Pharmaceuticals Inc

Ethics review

Status: Approved
Approval date: 03/07/2014
Contact:

Results

• Results available: Yes
• Date Posted: 20/12/2020
• Date Completed: 28/05/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005373-43/results