Open Label Study to Evaluate Safety and Efficacy of LUM001 in Patients With Primary Sclerosing Cholangitis

NCT02061540 | Completed Phase 2 Results

• 2 other identifiers: LUM001-4012014-005558-21
• Study Type: interventional
• Target: 27
• Locations: 3 countries
• Sites: 9

Brief Summary

The study is an open-label study in adults with primary sclerosing cholangitis to evaluate the safety, tolerability, and effect of 14-weeks of daily dosing of LUM001.

Conditions

Primary Sclerosing Cholangitis (PSC)

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  An Adverse Event (AE) was defined as 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 was considered to be related to the investigational drug product. TEAEs were AEs with a start date on or after the first dose of investigational product and started prior to the last dose of investigational product plus 14 days.

  From start of study drug administration until Week 18

• Change From Baseline in Fasting Serum Bile Acid Level at Week 14

  Serum bile acid levels were evaluated using blood samples collected.

  Baseline, Week 14

Secondary Outcomes (3)

• Change From Baseline in Liver Enzyme Levels in Serum

  Baseline, Week 14

• Change From Baseline in Bilirubin Levels at Week 14

  Baseline, Week 14

• Change From Baseline in Pruritus as Measured by Adult Itch Reported Outcome (ItchRO) Weekly Sum Score

  Baseline, Week 14

Other Outcomes (1)

• Change From Baseline for Other Biochemical Markers of Cholestasis: Total Cholesterol, Low Density Lipoprotein Cholesterol

  Baseline, Week 14

Study Arms (1)

LUM001

EXPERIMENTAL

LUM001 administered orally once each day

Drug: LUM001

Interventions

LUM001 DRUG

LUM001 oral dose

LUM001

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects between the ages of 18-80 years, inclusive.
• Diagnosis of PSC
• If inflammatory bowel disease (IBD) is present, disease activity ≤ 2 (normal to moderate), using the physician assessment on the Mayo ulcerative colitis (UC) disease activity score.
• Patients receiving azathioprine for intestinal bowel disease are eligible to participate in the study provided that they have had no IBD exacerbations for at least 6 months.
• Females of childbearing potential must have a negative serum pregnancy test \[β human chorionic gonadotropin (β-hCG)\] during screening and negative urine pregnancy test at the baseline/Day 0 visit.
• 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.
• Ability to read and understand English in order to use the study-related questionnaires and the text on the eDiary screen.
• Must be willing and able to use an eDiary daily for a minimum of 20 weeks.
• Must digitally accept the licensing agreement in the eDiary software at the outset of the study.
• Must complete at least 10 eDiary Adult ItchRO reports (AM or PM) during each of two consecutive weeks of the screening period prior to allocation to treatment (maximum possible reports = 14 per week).
• Access to phone for scheduled calls from study site.
• Must agree to comply with the study protocol procedures and provide written informed consent.

You may not qualify if:

• Small duct PSC (clinical biochemical and histological features compatible with PSC, but having a normal cholangiogram).
• Presence of a dominant stricture unless brushings and/or biopsies of the stricture are negative for dysplasia or malignancy within 6 months of screening.
• Surgical or endoscopic biliary tree interventions for treatment of clinically significant strictures within 6 months of screening.
• IBD flare (Mayo UC disease activity score \> 5 including endoscopic evaluation) within 3 months prior to screening.
• Secondary cause of sclerosing cholangitis (e.g., choledocholithiasis, post-surgical biliary stricture, intra-arterial chemotherapy, recurrent pancreatitis, IgG4 associated cholangiopathy, AIDS cholangiopathy).
• AST or ALT ≥ 5 x ULN at screening.
• History or presence of any other concomitant significant liver disease as assessed by the Investigator.
• Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease).
• Known history of human immunodeficiency virus (HIV) infection.
• The anticipated need for a surgical procedure within 20 weeks from randomization.
• Any female who is pregnant or lactating or who is planning to become pregnant within 20 weeks of randomization.
• History of cancer, except for basal or squamous cell carcinoma of the skin, or with any laboratory or physical exam or diagnostic procedure finding suggestive of current malignancy.
• Family history of any documented hereditary cancer syndrome.
• History of alcohol or other substance abuse within 1 year prior to screening.
• Receipt of an investigational drug, biologic, or medical device within 30 days prior to Screening, or 5 half-lives of the study agent, whichever is longer.

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (9)

Scripps Clinic

La Jolla, California, 92037, United States

Location

University of California at Davis

Sacramento, California, 95817, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

University of Calgary Liver Unit

Calgary, Alberta, T2N 4Z6, Canada

Location

University Health Network, Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

University of Birmingham

Birmingham, England, B15 2TT, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Related Publications (1)

• Bowlus CL, Eksteen B, Cheung AC, Thorburn D, Moylan CA, Pockros PJ, Forman LM, Dorenbaum A, Hirschfield GM, Kennedy C, Jaecklin T, McKibben A, Chien E, Baek M, Vig P, Levy C. Safety, tolerability, and efficacy of maralixibat in adults with primary sclerosing cholangitis: Open-label pilot study. Hepatol Commun. 2023 May 15;7(6):e0153. doi: 10.1097/HC9.0000000000000153. eCollection 2023 Jun 1.

  PMID: 37184523 DERIVED

MeSH Terms

Conditions

Cholangitis, Sclerosing

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Results Point of Contact

• Title: Study Physician
• Organization: Mirum

medinfo@mirumpharma.com

1 650-667-4085

Study Officials

• Study Director

  Mirum

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2014
• First Posted: February 13, 2014
• Study Start: March 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: March 29, 2019
• Results First Posted: April 12, 2017

Record last verified: 2019-03

Locations

US (5); GB (2); CA (2)