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

Primary Purpose

Primary Sclerosing Cholangitis (PSC)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
LUM001
Sponsored by
Mirum Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Sclerosing Cholangitis (PSC)

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female subjects between the ages of 18-80 years, inclusive.
  2. Diagnosis of PSC
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Ability to read and understand English in order to use the study-related questionnaires and the text on the eDiary screen.
  8. Must be willing and able to use an eDiary daily for a minimum of 20 weeks.
  9. Must digitally accept the licensing agreement in the eDiary software at the outset of the study.
  10. 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).
  11. Access to phone for scheduled calls from study site.
  12. Must agree to comply with the study protocol procedures and provide written informed consent.

Exclusion Criteria:

  1. Small duct PSC (clinical biochemical and histological features compatible with PSC, but having a normal cholangiogram).
  2. Presence of a dominant stricture unless brushings and/or biopsies of the stricture are negative for dysplasia or malignancy within 6 months of screening.
  3. Surgical or endoscopic biliary tree interventions for treatment of clinically significant strictures within 6 months of screening.
  4. IBD flare (Mayo UC disease activity score > 5 including endoscopic evaluation) within 3 months prior to screening.
  5. Secondary cause of sclerosing cholangitis (e.g., choledocholithiasis, post-surgical biliary stricture, intra-arterial chemotherapy, recurrent pancreatitis, IgG4 associated cholangiopathy, AIDS cholangiopathy).
  6. AST or ALT ≥ 5 x ULN at screening.
  7. History or presence of any other concomitant significant liver disease as assessed by the Investigator.
  8. Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease).
  9. Known history of human immunodeficiency virus (HIV) infection.
  10. The anticipated need for a surgical procedure within 20 weeks from randomization.
  11. Any female who is pregnant or lactating or who is planning to become pregnant within 20 weeks of randomization.
  12. 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.
  13. Family history of any documented hereditary cancer syndrome.
  14. History of alcohol or other substance abuse within 1 year prior to screening.
  15. 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.
  16. History of noncompliance with medical regimens, unreliability, mental instability or incompetence that could compromise the validity of informed consent or lead to noncompliance with the study protocol.
  17. 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.

Sites / Locations

  • Scripps Clinic
  • University of California at Davis
  • University of Colorado
  • University of Miami
  • Duke University
  • University of Calgary Liver Unit
  • University Health Network, Toronto Western Hospital
  • University of Birmingham
  • Royal Free Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LUM001

Arm Description

LUM001 administered orally once each day

Outcomes

Primary Outcome Measures

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.
Change From Baseline in Fasting Serum Bile Acid Level at Week 14
Serum bile acid levels were evaluated using blood samples collected.

Secondary Outcome Measures

Change From Baseline in Liver Enzyme Levels in Serum
Levels of liver enzymes such as Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) in serum were evaluated.
Change From Baseline in Bilirubin Levels at Week 14
Total Bilirubin and Direct (Conjugated) Bilirubin levels were evaluated.
Change From Baseline in Pruritus as Measured by Adult Itch Reported Outcome (ItchRO) Weekly Sum Score
The Adult ItchRO instrument was completed twice daily using an electronic diary (eDiary). Each morning and evening score had a range from 0-10, with the higher score indicating increasing itch severity. The following was used for assessing the Adult ItchRO daily score: The score which represented the most severe itching for the day (morning or evening) was taken for each day as the daily score (maximum daily score of 10); If only 1 of the 2 scores was available for the day, the score that was available was used as the daily score; If both the morning and the evening scores were missing, the score was considered missing for the day.

Full Information

First Posted
February 11, 2014
Last Updated
March 15, 2019
Sponsor
Mirum Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02061540
Brief Title
Open Label Study to Evaluate Safety and Efficacy of LUM001 in Patients With Primary Sclerosing Cholangitis
Acronym
CAMEO
Official Title
A Pilot, Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of LUM001, an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTi), in Patients With Primary Sclerosing Cholangitis
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mirum Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis (PSC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LUM001
Arm Type
Experimental
Arm Description
LUM001 administered orally once each day
Intervention Type
Drug
Intervention Name(s)
LUM001
Intervention Description
LUM001 oral dose
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
From start of study drug administration until Week 18
Title
Change From Baseline in Fasting Serum Bile Acid Level at Week 14
Description
Serum bile acid levels were evaluated using blood samples collected.
Time Frame
Baseline, Week 14
Secondary Outcome Measure Information:
Title
Change From Baseline in Liver Enzyme Levels in Serum
Description
Levels of liver enzymes such as Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) in serum were evaluated.
Time Frame
Baseline, Week 14
Title
Change From Baseline in Bilirubin Levels at Week 14
Description
Total Bilirubin and Direct (Conjugated) Bilirubin levels were evaluated.
Time Frame
Baseline, Week 14
Title
Change From Baseline in Pruritus as Measured by Adult Itch Reported Outcome (ItchRO) Weekly Sum Score
Description
The Adult ItchRO instrument was completed twice daily using an electronic diary (eDiary). Each morning and evening score had a range from 0-10, with the higher score indicating increasing itch severity. The following was used for assessing the Adult ItchRO daily score: The score which represented the most severe itching for the day (morning or evening) was taken for each day as the daily score (maximum daily score of 10); If only 1 of the 2 scores was available for the day, the score that was available was used as the daily score; If both the morning and the evening scores were missing, the score was considered missing for the day.
Time Frame
Baseline, Week 14
Other Pre-specified Outcome Measures:
Title
Change From Baseline for Other Biochemical Markers of Cholestasis: Total Cholesterol, Low Density Lipoprotein Cholesterol
Description
Total cholesterol (TC) level and low density lipoprotein cholesterol (LDLC) level were considered as biochemical markers of cholestasis.
Time Frame
Baseline, Week 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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. History of noncompliance with medical regimens, unreliability, mental instability or incompetence that could compromise the validity of informed consent or lead to noncompliance with the study protocol. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Mirum
Official's Role
Study Director
Facility Information:
Facility Name
Scripps Clinic
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
University of California at Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
University of Calgary Liver Unit
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
University Health Network, Toronto Western Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
Facility Name
University of Birmingham
City
Birmingham
State/Province
England
ZIP/Postal Code
B15 2TT
Country
United Kingdom
Facility Name
Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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