A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate LUM001, an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTi), in Combination with Ursodeoxycholic Acid (UDCA) in Patients with Primary Biliary Cirrhosis
This is a randomized, double-blind, placebo-controlled, Phase 2 proof of concept and safety study in adults with PBC. The study is designed to investigate the effects of LuM001 in combination with uDCa on pruritus, liver enzymes, and other biochemical markers associated with PBC, compared to placebo, following daily dosing over a 13-week period.
Two dose cohorts are planned. in each cohort, eligible subjects will be randomized in a ratio of 2:1 (active to placebo). Randomization will be stratified by aLP level (aLP [GreaterThanorequalTo] 2x uLn) at screening.
Cohort a: 10 mg LuM001 + uDCa, or placebo +uDCa
Cohort B: 5 or 20 mg LuM001 +uDCa, or placebo +uDCa
The study will be opened with enrollment in Cohort a. Dose selection for Cohort B will be informed by the tolerability of 10 mg LuM001 in Cohort a.
For all subjects, oral administration of uDCa will be according to their pre-study regimen throughout the study. no changes to uDCa regimen or permitted prestudy medications are allowed during the course of the study.
1. Male or female subjects between the ages of 18-80 years, inclusive
2. Diagnosis of PBC [consistent with the American Association for the Study of Liver Disease (AASLD, Section 16.3) Practice Guidelines Practice Guidelines; (Lindor,Gershwin, Poupon, Kaplan, Bergasa, & Heathcote, 2009), as demonstrated by the
documented history of at least 2 of the following diagnostic factors:
a. History of elevated alkaline phosphatase (ALP) levels
b. Presence of anti-mitochondrial antibodies (AMA) with a titer >=1:40
c. Liver biopsy consistent with PBC if a biopsy has been performed
d. For patients who are AMA negative, a liver biopsy diagnostic for PBC
3. A previous ultrasound (or equivalent imaging modality) of the biliary tree that excludes biliary obstruction and overt malignancy within 12 months of the screening visit
4. An average daily score > 4.0 on the Adult Itch Reported Outcome (Adult ItchROTM) questionnaire (maximum possible daily score of 10), for each of two consecutive weeks in the screening period using the eDiary (see Section 8.4.1).
5. Taking ursodeoxycholic acid (UDCA) for at least 6 months (stable dose for >= 3 months prior to Day 0), or unable to tolerate UDCA (no UDCA >= 3 months prior to Day 0)
6. If using any of the following medications, must be on a stable dose for the period
indicated and expected to remain on the same dose and regimen throughout the
a. For 30 days prior to screening: rifampin, antihistamines, opiate antagonists
b. For 90 days prior to screening: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs)
7. Females of childbearing potential must have a negative serum pregnancy test [[BETA] human chorionic gonadotropin ([BETA]-hCG)] during screening and negative urine pregnancy test at the baseline visit
8. Sexually active females must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use an effective method (<= 1% failure rate) of contraception during the trial. Effective methods of contraception are considered
c. Hormonal (e.g., contraceptive pill, patch, intramuscular implant or injection) provided subject has been on stable therapy for at least 3 months; or
d. Barrier method, e.g., (a) condom (male or female) or (b) diaphragm, with spermicide; or
e. Intrauterine device (IUD); or
f. Vasectomy (partner)
9. Ability to read and understand English or Spanish in order to use the study-related questionnaires
10. Ability to read the text on the eDiary screen
11. Must be willing and able to use an eDiary daily for a minimum of 20 weeks
12. Must digitally accept the licensing agreement in the eDiary software at the outset of the study
13. Must complete at least 10 eDiary Adult ItchRO reports (AM or PM) during each of two consecutive weeks of the screening period prior to randomization (maximum possible reports = 14 per week)
14. Access to phone for scheduled calls from study site
15. Must agree to comply with the study protocol and provide written informed consent