Alagille Syndrome, Cholestatic Liver Disease, Progressive Familial Intrahepatic Cholestasis
Conditions
Keywords
PFIC, ALGS, Maralixibat, Bile Duct Diseases, Liver Diseases, Biliary Tract Diseases, Pediatric
Brief summary
This study is designed to assess whether the investigational drug maralixibat, is safe and well tolerated in children \<12 months of age with Alagille Syndrome \[ALGS\] or Progressive Familial Intrahepatic Cholestasis \[PFIC\].
Detailed description
This is an open label study where all participants will receive maralixibat treatment.
Interventions
DRUGMaralixibat
Maralixibat chloride provided in the form of an oral solution (i.e., 5, 10, 15, and 20 mg/mL) * 400 μg/kg maralixibat chloride is equivalent to 380 µg/kg maralixibat free base * 600 μg/kg maralixibat chloride is equivalent to 570 µg/kg maralixibat free base
Sponsors
Mirum Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single group with 2 cohorts - ≥ 6 participants each from ALGS and PFIC.
Eligibility
Sex/Gender
ALL
Age
0 Days to 364 Days
Healthy volunteers
No
Inclusion criteria
1. Body weight of ≥2.5 kg 2. \<12 months of age at the baseline visit (ROW). \>31 days and \<12 months of age at the baseline visit (US). 3. Gestational age ≥36 weeks at birth. For children born with gestational age between 32 and 36 weeks, a postmenstrual age of ≥36 weeks is required. 4. Diagnosis of PFIC or ALGS
Exclusion criteria
1. Predicted complete absence of bile salt excretion pump (BSEP) function 2. History of surgical disruption of the enterohepatic circulation 3. History of liver transplant or imminent need for liver transplant 4. Decompensated cirrhosis 5. 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), per investigator discretion 6. Presence of other significant liver disease or any other conditions or abnormalities which, in the opinion of the investigator or medical monitor, may compromise the safety of the participant or interfere with the participant's participation in or completion of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Treatment-emergent Adverse Events [TEAEs] | From Baseline through to Week 13 | TEAEs = Treatment-emergent Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Serum Bile Acid (sBA) Levels | From Baseline through to Week 13 | sBA = serum bile acid |
| To Evaluate the Effect on Liver Enzymes (ALT) | From Baseline through to Week 13 | ALT= alanine aminotransferase. |
| Change From Baseline to Week 13 in Lipid-Soluble Vitamins (LSVs) - Vitamin E | From Baseline through to Week 13 | Change from baseline to Week 13 in vitamin E. |
| Maximum Level of Maralixibat Concentration in Plasma From Baseline to Week 13 for ALGS | At Baseline, Week 6, Week 10, Week 13 or Early Termination Visit | BID=twice daily; QD=once daily. Systemic concentrations of maralixibat in plasma were determined at the following visits: * Approximately 2.5 hours after the morning dose at Week 0/Day 1 of dosing * Before dosing and \~2.5 hours after the morning dose at Week 6, Week 10, and Week 13 Stable dosing occurred at 400 μg/kg QD for ALGS or at the highest tolerated dose. Note: The values added in section Measured Values are for maralixibat dose of 400 µg/kg QD. |
| To Evaluate the Effect on Liver Enzymes (AST) | From Baseline through to Week 13. | AST= aspartate aminotransferase |
| To Evaluate the Effect on Bilirubin | From Baseline through to Week 13 | Bilirubin |
| Change From Baseline to Week 13 in Lipid-Soluble Vitamins (LSVs) - Vitamin A | From Baseline through to Week 13 | Change from baseline to Week 13 in vitamin A |
| Change From Baseline to Week 13 in Lipid-Soluble Vitamins (LSVs) - Vitamins D and K | From Baseline through to Week 13 | Change from baseline to Week 13 in vitamins D and K. |
| Maximum Level of Maralixibat Concentration in Plasma From Baseline to Week 13 for PFIC | At Baseline, Week 6, Week 10, Week 13 or Early Termination Visit | BID=twice daily; QD=once daily. Systemic concentrations of maralixibat in plasma were determined at the following visits: * Approximately 2.5 hours after the morning dose at Week 0/Day 1 of dosing * Before dosing and \~2.5 hours after the morning dose at Week 6, Week 10, and Week 13 Stable dosing occurred at 300 μg/kg QD, 300 μg/kg BID and 600 μg/kg BID for PFIC or at the highest tolerated dose. Note: The values added in section Measured Values are for maralixibat dose of 600 µg/kg BID. |
Countries
Belgium, Brazil, France, Mexico, Poland, United Kingdom, United States
Participant flow
Recruitment details
A total of 27 participants were enrolled in the study, across 10 sites in 6 countries (Belgium, Brazil, France, Poland, United Kingdom, and United States), 17 patients in the ALGS Cohort and 10 in the PFIC Cohort.
Pre-assignment details
The screening period starts when informed consent (by the legally authorized representative) is signed. The duration of the screening period is up to 4 weeks, during which all procedures listed for the screening visit in the schedule of assessment must be completed.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized Infants and toddlers (28 days-23 months) | 10 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants |
| Age, Customized Preterm newborn - gestational age < 37 weeks | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment Belgium | 0 participants |
| Region of Enrollment Brazil | 0 participants |
| Region of Enrollment France | 1 participants |
| Region of Enrollment Poland | 3 participants |
| Region of Enrollment United Kingdom | 5 participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 10 |
| other Total, other adverse events | 16 / 17 | 10 / 10 |
| serious Total, serious adverse events | 6 / 17 | 2 / 10 |
Outcome results
None listed